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Isotopomer distribution analysis using [U-13C]glucose in HuH7 cells with or without ectopic FBP1 expression.

Promoter methylation and copy number profiles of FBP1 in liver cancer cell lines from the Cancer Cell Line Encyclopedia.

Supplementary Materials and Methods, and Legends for Supplementary Figures.

The treatment of early breast cancer using oncoplastic breast surgery (OBS) has been gradually increasing in popularity and is recognized for its efficacy in local control and excellent cosmetic results. We herein report a useful technique for obtaining symmetry of the breast shape for an early breast lesion located in an outer area, close to the nipple-areola, in a Japanese patient with ptotic, fatty breasts. We designed two equilateral triangles: one just upon the resected area and the other on the axilla. They were located on a straight line, with one top pointed to the cranial side and one to the caudal side. A crescent area around the areola was de-epithelialized in the 12 o’clock and 6 o’clock directions. Columnar-shaped breast tissue and an equilateral triangular skin flap and fatty tissue were removed together. To fill the defect, a skin-glandular flap was slid horizontally after suturing the inframammary line. Although an incision scar was formed on the breast and lateral chest wall in a Z-shape, this new technique was able to achieve not only cancer control but also excellent cosmetic results.

Our recent research has revealed that passenger strands of certain microRNAs (miRNAs) function as tumor-suppressive miRNAs in cancer cells, e.g., miR-101-5p, miR-143-5p, miR-144-5p, miR-145-3p, and miR-150-3p. Thus, they are important in cancer pathogenesis. Analysis of the miRNA expression signature of breast cancer (BrCa) showed that the expression levels of two miRNAs derived from pre-miR-99a (miR-99a-5p and miR-99a-3p) were suppressed in cancerous tissues. The aim of this study was to identify oncogenic genes controlled by pre-miR-99a that are closely involved in the molecular pathogenesis of BrCa. A total of 113 genes were identified as targets of pre-miR-99a regulation (19 genes modulated by miR-99a-5p, and 95 genes regulated by miR-99a-3p) in BrCa cells. Notably, FAM64A was targeted by both of the miRNAs. Among these targets, high expression of 16 genes (C5orf22, YOD1, SLBP, F11R, C12orf49, SRPK1, ZNF250, ZNF695, CDK1, DNMT3B, TRIM25, MCM4, CDKN3, PRPS, FAM64A, and DESI2) significantly predicted reduced survival of BrCa patients based upon The Cancer Genome Atlas (TCGA) database. In this study, we focused on FAM64A and investigated the relationship between FAM64A expression and molecular pathogenesis of BrCa subtypes. The upregulation of FAM64A was confirmed in BrCa clinical specimens. Importantly, the expression of FAM64A significantly differed between patients with Luminal-A and Luminal-B subtypes. Our data strongly suggest that the aberrant expression of FAM64A is involved in the malignant transformation of BrCa. Our miRNA-based approaches (identification of tumor-suppressive miRNAs and their controlled targets) will provide novel information regarding the molecular pathogenesis of BrCa.

The treatment of early breast cancer using breast conservation therapy (BCT) commonly ensures local control and acceptable cosmetic results. We herein report a useful technique to obtain symmetry of the breast shape and a level inframammary line and nipple-areola, which achieved excellent results. Six Japanese patients with early breast cancer located on the upper area of the breast were enrolled into this study. A triangle-shaped area of skin was removed together with cancerous and healthy-surrounding breast tissue. Two crescents were designed and de-epithelialized in the directions of 9 o'clock and 3 o'clock. The width of the crescent was decided to be the same as a half or the length of the base of a triangle to be removed. After partial mastectomy, the inner and outer glandular flaps were horizontally sutured. The operations were simple to perform and were not associated with any postoperative complications. Oncoplastic breast surgery combining partial mastectomy with triangular skin resection and re-centralization of the nipple-areola was useful for patients with breast cancer on the upper quadrant area of non-ptotic breasts.

The development and application of cancer immunotherapy to pancreatic cancer has not progressed because its efficacy has not been proven in clinical trials. In this study, we aimed to explore potential targets of immune checkpoint inhibitor therapy for pancreatic cancer treatment.We collected resected specimens from 40 patients with pancreatic cancer who underwent resection at our Institution without any preoperative treatment. We evaluated the expression of molecules in the programmed death receptor-1 (PD-1), T cell immunoglobulin mucin-3 (Tim-3)/Galectin-9, and CD155/T cell immunoreceptor with Ig and ITIM domains (TIGIT) pathways using immunohistochemical staining. The correlation between the expression pattern of these molecules and patient prognosis were assessed using Kaplan-Meier analysis.An increased number of CD8Modifications in the immune environment to increase T cell infiltration into tumors could result in the PD-1 pathway becoming a potential target to treat pancreatic cancer using immune checkpoint inhibition.

Background The treatment of early breast cancer using breast conservation therapy (BCT) commonly ensures local control and acceptable cosmetic results. We report a useful technique including the use of a thoracodorsal adipofascial cutaneous flap for reconstructing defects in the outer quadrant area after partial mastectomy, which achieved excellent results. Methods During the past 15 years, some modifications have been added to the original method at a rate of one modification every 2–5 years. We classified these modifications into the original method and four modified methods. Modification I: addition of a crescent-shaped dermis on the distant edge of the thoracodorsal adipofascial flap (TDAFF), Modification II: addition of a crescent-shaped dermis on the proximal edge of the TDAFF, Modification III: addition of inframammary formation plus Modification II, and Modification IV: change of a crescent-shaped dermis to a Benz-shaped (shaped like the Mercedes Benz logo) one plus Modification III. We compared the plastic period, postoperative complications, oncological results, and cosmetic results among the original and four modified groups. Results The patient number was 26, 9, 15, 23, and 10 in the original and Modification I, II, III, and IV groups, respectively. The median observation period was 115, 92, 67, 51, and 32 months, respectively. Postoperative complications were seen in 5 (19%), 0, 2 (13%), 1 (5%), and 0 patients, respectively. Local recurrence was seen in 3 (12%), 0, 0, 0, and 0 patients, respectively. Distant recurrence was seen in 1 (4%), 1 (11%), 3 (20%), 0, and 0 patients, respectively. Cosmetic results evaluated as good–excellent were seen in 19 (73%), 5 (56%), 11 (73%), 19 (83%), and 10 (100%) patients, respectively. Conclusions Oncoplastic surgery using an immediate volume replacement technique with a thoracodorsal adipofascial flap was improved by adding some modifications.

In 2011, we developed bidirectional approach video-assisted neck surgery (BAVANS) for endoscopic thyroid cancer surgery. BAVANS combines two different approach pathways at 180 degrees to the cervical lesion for endoscopic thyroidectomy and complete cervical lymphadenectomy. We reported previously that the cranio-caudal approach is extremely useful for endoscopic complete lymph node dissection around the trachea. In 2014, we upgraded the initial BAVANS for better maneuverability and quality of lymph node dissection. A new high-tech rigid endoscope with a variable viewing direction (EndoCAMeleon™), has enabled us to reduce the camera port in the anterior neck while keeping the easy maneuverability and the same quality of central lymph node dissection (LND) as with the initial BAVANS. Endoscopic thyroid cancer surgery is now evolving concurrently with new visual technology.

Breast cancer is primarily classified into ductal and lobular types, as well as into noninvasive and invasive cancer. Invasive cancer involves lymphatic and hematogenous metastasis. In breast cancer patients with distant metastases, a neutrophil-derived serine protease; cathepsin G (Cat G), is highly expressed in breast cancer cells. Cat G induces cell migration and multicellular aggregation of MCF-7 human breast cancer cells; however, the mechanism is not clear. Recently, platelet-activating factor (PAF)-acetylhydrolase (PAF-AH), the enzyme responsible for PAF degradation, was reported to be overexpressed in some tumor types, including pancreatic and breast cancers. In this study, we investigated whether PAF-AH is involved in Cat G-induced aggregation and migration of MCF-7 cells. We first showed that Cat G increased PAF-AH activity and elevated PAFAH1B2 expression in MCF-7 cells. The elevated expression of PAFAH1B2 was also observed in human breast cancer tissue specimens by immunohistochemical analysis. Furthermore, knockdown of PAFAH1B2 in MCF-7 cells suppressed the cell migration and aggregation induced by low concentrations, but not high concentrations, of Cat G. Carbamoyl PAF (cPAF), a nonhydrolyzable PAF analog, completely suppressed Cat G-induced migration of MCF-7 cells. In addition, PAF receptor (PAFR) inhibition induced cell migration of MCF-7 cells even in the absence of Cat G, suggesting that Cat G suppresses the activation of PAFR through enhanced PAF degradation due to elevated expression of PAFAH1B2 and thereby induces malignant phenotypes in MCF-7 cells. Our findings may lead to a novel therapeutic modality for treating breast cancer by modulating the activity of Cat G/PAF signaling.

A 39-year-old gravida 1 para 1 pregnant Japanese woman underwent skin-sparing mastectomy and axillary lymph node dissection with immediate breast reconstruction (IBR) using a tissue expander (TE) at 32 weeks of pregnancy under general anesthesia. Inserted TE (300 cc) was expanded during breast feeding while the volume was 240 cc of the resected breast tissue. One month after delivery, 2 months after surgery, the contralateral healthy breast increased in size and the inframammary line was deviated toward a caudal site which was larger than 300 cc-inflated TE. She stopped breast feeding to receive a systemic chemotherapy after one months-breast feeding. At 3 months after delivery, the healthy breast size was smaller than the 250 cc-expanded breast and both the inframammary lines were at the same level. She was diagnosed local recurrence 3 month-postoperatively, so we resected the recurrent lesion and exchanged TE to silicon breast implant immediately. Finally, a good symmetry was obtained after insertion of the 220 cc SBI. At an IBR using TE, we should know the dynamic change of breast volume and the level of inframammary line of the healthy breast during those phases of pregnancy, delivery, and nursing.

Background Although a few cases of accessory breast cancer (ABC) have been reported, most were in the axillary region. We encountered an extremely rare case of ABC in the inframammary region (IMR). Case presentation The patient was a 68-year-old postmenopausal woman who had noticed a congenital accessory nipple in her left IMR with slight, occasional discharge 20 years ago. Recently, she noticed a mass under the accessory nipple and visited a nearby clinic; fine-needle aspiration cytology of the mass revealed that it was malignant. She presented to our department 2 weeks after she had noticed the mass. Physical and imaging examinations showed an irregular tumor mass 1.7 × 1.4 × 1.0 cm in size connected to the accessory nipple beneath the left normal breast. Neither distant metastasis nor lymph node swelling was observed. Ultrasound-guided core needle biopsy revealed the mass to be invasive ductal carcinoma. We diagnosed her tumor as ABC in the left IMR; cT1cN0M0: stage IA. Curative wide resection with sentinel node biopsy was performed. Intraoperative evaluation of the frozen section revealed a hot and green ipsilateral axillary lymph node that was free from carcinoma; therefore, nodal dissection was avoided. Histopathological examination including immunochemical staining revealed that the tumor was invasive ductal carcinoma arising from the accessory breast tissue, scirrhous type, 1.7 × 1.4 × 1.0 cm in size, with a solid intraductal component. There was no lymphovascular infiltration, and the surgical margin was 1.5 cm or more. The tumor was estrogen and progesterone receptor-positive, Her2/neu-negative, and had a Ki-67 labeling index of 20%. There was no involvement of the three hot and/or green nodes. The final classification was pT1cN0(sn)M0: stage IA. Letrozole 2.5 mg/day will be administered for 5 years as adjuvant hormonal therapy. Conclusions A cutaneous and/or subcutaneous lesion except for proper breast tissue on the milk line, or mammary ridge from axilla to groin may be an accessory breast tissue. Its serial abnormalities must be worried malignant potential to ductal carcinoma which needs some imaging and pathological examinations for definitive diagnosis and appropriate treatment according to the usual orthotopic breast cancer without delay.

Introduction: Endoscopic thyroid surgery through the extracervical approach is a safe and well-accepted technique. Endoscopic techniques have to be applied widely in thyroid cancer treatme...

Background/aim Locoregional recurrence (LRR) of breast cancer is reported to occur at a rate of 5%-15%. Wide excision of LRR is the recommended treatment, which can increase the probability of subsequent local control. Herein, we describe a surgical technique wherein a pedicled skin and subcutaneous flap close the skin defect after resection of a breast cancer LRR without use of a skin graft. Patients and methods We reviewed four patients who underwent surgical resection using a pedicled rotation flap for chest wall recurrence after mastectomy. Results The surgical margin was set 2 cm apart from the tumor margin. After resection of tumor from the chest wall, we formed an adjacent pedicled flap and rotated the flap to the skin defect. There were no post-operative complications, including wound necrosis. Conclusion Surgical resection with a pedicled rotation flap for post-mastectomy breast cancer LRR is a highly feasible way to achieve complete resection.

Oncoplastic breast surgery (OBS), which combines the concepts of oncologic and plastic surgery, is becoming more common worldwide. We report the results of OBS in a Japanese patient with early breast cancer located on the outer lower quadrant area. We performed OBS combining partial mastectomy with immediate breast reshaping using multiple adipofascial cutaneous flaps and free dermal fat graft because she refused any other OBS. We selected three local flaps to repair the defect. Perioperative and postoperative complications were not seen. The cosmetic findings 3 years after surgery were not excellent, but the patient was satisfied with the results. OBS combining partial mastectomy with immediate breast reshaping using a combination of several flaps was successfully performed in a patient with early breast cancer.

Background: Human T-cell lymphotropic virus type 1 (HTLV-1) is a retrovirus that causes adult T-cell leukemia/lymphoma (ATL), an aggressive form of T-cell malignancy. The relationship between HTLV-1 infection and cancer progression is controversial. HTLV-1 encodes oncogenic protein TAX1 and it is hypothesized that HTLV-1 infection is associated with breast cancer progression. In this study, we evaluated the relationship between HTLV-1 infection and clinicopathological factors in breast cancer patients. Methods: We retrospectively analyzed 610 patients with primary breast cancer who underwent surgical treatment without preoperative chemotherapy at Kagoshima University Hospital between January 2001 and January 2015. Results: When patients with and without HTLV-1 infection were compared, no differences in clinicopathological factors were observed, except for age. Disease-free survival and overall survival rates did not differ between groups. Conclusions: HTLV-1–positive patients were significantly older than HTLV-1–negative patients. It was supposed to be due to the fact that the HTLV-1 infection rate is decreasing. Any effect of HTLV-1 infection on breast cancer progression appears to be negligibly small.

Background & Aims Oropharyngeal and esophageal squamous cell carcinomas, especially the latter, are a lethal disease, featuring intratumoral cancer cell heterogeneity and therapy resistance. To facilitate cancer therapy in personalized medicine, three-dimensional (3D) organoids may be useful for functional characterization of cancer cells ex vivo. We investigated the feasibility and the utility of patient-derived 3D organoids of esophageal and oropharyngeal squamous cell carcinomas. Methods We generated 3D organoids from paired biopsies representing tumors and adjacent normal mucosa from therapy-naïve patients and cell lines. We evaluated growth and structures of 3D organoids treated with 5-fluorouracil ex vivo. Results Tumor-derived 3D organoids were grown successfully from 15 out of 21 patients (71.4%) and passaged with recapitulation of the histopathology of the original tumors. Successful formation of tumor-derived 3D organoids was associated significantly with poor response to presurgical neoadjuvant chemotherapy or chemoradiation therapy in informative patients (P = 0.0357, progressive and stable diseases, n = 10 vs. partial response, n = 6). The 3D organoid formation capability and 5-fluorouracil resistance were accounted for by cancer cells with high CD44 expression and autophagy, respectively. Such cancer cells were found to be enriched in patient-derived 3D organoids surviving 5-fluorouracil treatment. Conclusions The single cell-based 3D organoid system may serve as a highly efficient platform to explore cancer therapeutics and therapy resistance mechanisms in conjunction with morphological and functional assays with implications for translation in personalized medicine., Graphical abstract

Triple-negative breast cancer (TNBC) is an aggressive type of cancer associated with a poor prognosis. Identification of novel therapeutic targets in TNBC is urgently needed. Here, we investigated the microRNA (miRNA) expression signature of TNBC using clinical specimens. In total, 104 miRNAs (56 upregulated and 48 downregulated) were significantly dysregulated in TNBC tissues; miR-204-5p showed the most dramatic downregulation. We then examined the antitumor roles of miR-204-5p in breast cancer (BC) cells. Notably, cancer cell migration and invasion were significantly reduced by ectopic expression of miR-204-5p in BC cells. Genome-wide gene expression analysis and in silico database search revealed that 32 genes were putative miR-204-5p targets. High expression of AP1S3, RACGAP1, ELOVL6, and LRRC59 was significantly associated with poor prognosis in patients with BC, and adaptor-related protein complex 1 sigma 3 subunit (AP1S3) was directly regulated by miR-204-5p, as demonstrated by luciferase reporter assays. AP1S3 overexpression was detected in TNBC clinical specimens and enhanced cancer cell aggressiveness. We further analyzed downstream RNA networks regulated by AP1S3 in BC cells. Overall, this miRNA signature is expected to be an effective tool for identification of miRNA-mediated molecular mechanisms of TNBC pathogenesis.

Background/aim Circulating microRNAs (miRs) in blood have been highlighted as diagnostic, prognostic and predictive biomarkers for "Precision medicine". This study aimed to explore the possibility of using circulating precursor miRs (pre-miRs) as clinical biomarkers of recurrence in breast cancer. Materials and methods We performed miR microarray analyses of circulating miRs in blood from patients with or without recurrence of breast cancer and identified miR-488-5p as a recurrence-related miR. Then, the expression levels of pre-miR-488 or miR-488-5p were measured by RT-qPCR and the clinicopathological and prognostic significance of circulating pre-miR-488 was assessed in the blood of breast cancer patients. Results A positive correlation was noted between pre-miR-488 and miR-488-5p expression in blood. In 330 cases of surgically-treated breast cancer, high expression of circulating pre-miR-488 was an independent poor prognostic factor for recurrence-free survival. Conclusion Circulating pre-miR-488 expression could be a novel prognostic biomarker for predicting recurrence in breast cancer patients.

Background Severe mental disorders are thought to affect the diagnosis and treatment of breast cancer because of their lower awareness and understanding of the disease and their reduced ability to cooperate with medical staff. We analyzed the clinical features of patients with breast cancer and pre-existing mental disorders such as schizophrenia, dementia, and intellectual disability. Patients and methods: We reviewed the records of 46 patients who were diagnosed with schizophrenia, dementia, or intellectual disability, before being diagnosed with breast cancer. Three patients had more than 2 mental disorders. All patients underwent curative surgical treatment between September 1992 and January 2015. Patients' clinicopathological information was compared with a control group of 727 breast-cancer patients without mental disorders seen during the same period. Results Patients with mental disorders were less likely to be aware of their own breast cancer; the lesions were often found by other people such as family, care staff, and medical staff. Breast cancer patients with mental disorders had significantly more advanced T factors and overall stage at the time of surgery than their counterparts without mental illness, more patients underwent total mastectomy, and fewer patients underwent postoperative adjuvant chemotherapy and radiation. Biological markers such as estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 (HER2) expression were not significantly different between groups. Disease-free survival and overall survival were not significantly different between groups. Conclusion Patients with mental disorders receive less postoperative adjuvant chemotherapy; however, their outcomes were not worse than those of patients without mental disorders.

Background /Objectives: The lung is a major metastatic site of pancreatic cancer (PC). We aimed to assess the features and prognosis of patients with PC according to the recurrence pattern and the effect of resection of recurrent lung lesion. Methods We enrolled 168 PC patients who had undergone macroscopically curative resection. All resected lung tumors were evaluated immunohistochemically for expressions of thyroid transcription factor-1 (TTF-1) and napsin A. Results The most common site of first recurrence was the liver and local site, followed by the lung, peritoneum, and lymph node. Lung recurrence was observed significantly later than was liver recurrence. The median survival time (MST) after recurrence in patients with first recurrence in the lung was significantly longer than MST in patients with first recurrence in the liver (15.2 months vs 5.2 months, p = 0.039). Seven patients with lung recurrence underwent resection of the recurrent lesion. Surgical resection of single metastasis limited to the lung showed favorable overall survival after recurrence (MST = 36.5 months). Patients with single metastasis limited to the lung showed significantly lower value of FDG-PET SUVmax of the primary pancreatic tumor. Conclusions Patients with first recurrence in the lung showed better prognosis than did patients with first recurrence in the liver. Single metastasis limited to the lung could benefit from surgical resection and was significantly associated with lower FDG-PET SUVmax of the primary pancreatic tumor.

Aberrantly expressed microRNA (miRNA) are known to disrupt intracellular RNA networks in cancer cells. Exploring miRNA‐dependent molecular networks is a major challenge in cancer research. In this study, we performed RNA‐sequencing of breast cancer (BrCa) clinical specimens to identify tumor‐suppressive miRNA in BrCa. In total, 64 miRNA were identified as candidate tumor‐suppressive miRNA in BrCa cells. Analysis of our BrCa signature revealed that several miRNA duplexes (guide strand/passenger strand) derived from pre‐miRNA were downregulated in BrCa tissues (e.g. miR‐99a‐5p/‐3p, miR‐101‐5p/‐3p, miR‐126‐5p/‐3p, miR‐143‐5p/‐3p, and miR‐144‐5p/‐3p). Among these miRNA, we focused on miR‐101‐5p, the passenger strand of pre‐miR‐101, and investigated its tumor‐suppressive roles and oncogenic targets in BrCa cells. Low expression of miR‐101‐5p predicted poor prognosis in patients with BrCa (overall survival rate: P = 0.0316). Ectopic expression of miR‐101‐5p attenuated aggressive phenotypes, e.g. proliferation, migration, and invasion, in BrCa cells. Finally, we identified seven putative oncogenic genes (i.e. High Mobility Group Box 3, Epithelial splicing regulatory protein 1, GINS complex subunit 1 (GINS1), Tumor Protein D52, Serine/Arginine‐Rich Splicing Factor Kinase 1, Vang‐like protein 1, and Mago Homolog B) regulated by miR‐101‐5p in BrCa cells. The expression of these target genes was associated with the molecular pathogenesis of BrCa. Furthermore, we explored the oncogenic roles of GINS1, whose function had not been previously elucidated, in BrCa cells. Aberrant expression of GINS1 mRNA and protein was observed in BrCa clinical specimens, and high GINS1 expression significantly predicted poor prognosis in patients with BrCa (overall survival rate: P = 0.0126). Knockdown of GINS1 inhibited the malignant features of BrCa cells. Thus, identification of tumor‐suppressive miRNA and molecular networks controlled by these miRNA in BrCa cells may be an effective strategy for elucidation of the molecular pathogenesis of this disease., We showed that miR‐101‐5p acted as an anti‐tumor miRNA in breast cancer (BrCa) cells through targeting several oncogenic genes (i.e. High Mobility Group Box 3, Epithelial splicing regulatory protein 1, GINS complex subunit 1 (GINS1), Tumor Protein D52, Serine/Arginine‐Rich Splicing Factor Kinase 1, Vang‐like protein 1, and Mago Homolog B). Aberrant expression of GINS1 mRNA and protein was observed in BrCa clinical specimens, and high GINS1 expression significantly predicted poor prognosis in patients with BrCa (overall survival rate: P = 0.0126).

Introduction Endoscopic thyroidectomy is a well-established surgical technique that is mainly performed for benign thyroid disease. We considered that endoscopic surgery could also be widely indicated for the treatment of thyroid cancer. We herein describe our new bidirectional approach of video-assisted neck surgery (BAVANS) for complete central node dissection in endoscopic thyroid cancer surgery. Methods BAVANS involves two different directional pathways to the cervical lesion. Before lymph node dissection, we perform endoscopic thyroidectomy via a conventional gasless precordial or axillary approach. After thyroidectomy, the surgeon repositions by the head of the patient and inserts three ports in front of the upper neck lesion in the submandibular area to approach the paratracheal lesion from an overhead-to-caudal direction. Results BAVANS allows for an excellent craniocaudal view and easy access to the peritracheal lymph nodes. Sixteen patients with papillary thyroid cancer underwent BAVANS and progressed satisfactorily after surgery. Of those patients, eight underwent total or near total thyroidectomy, and five patients underwent bilateral central node dissection. The average number of retrieved lymph nodes with unilateral central node dissection was nine, which was higher than that achieved with conventional open surgery. All patients began oral intake within 5 h after surgery. Postoperative Horner syndrome occurred in one patient. No other complications were noted. Conclusions BAVANS is a very effective surgical procedure that many endoscopic surgeons can perform safely and easily. It has both a cosmetic advantage and excellent curability in endoscopic thyroid cancer surgery.

Oncoplastic breast surgery (OBS), which combines the concepts of oncologic and plastic surgery, is becoming more common worldwide. We report the results of OBS in a Japanese patient with early breast cancer located on the outer lower quadrant area. We performed OBS combining partial mastectomy with immediate breast reshaping using multiple adipofascial cutaneous flaps and free dermal fat graft because she refused any other OBS. We selected three local flaps to repair the defect. Perioperative and postoperative complications were not seen. The cosmetic findings 3 years after surgery were not excellent, but the patient was satisfied with the results. OBS combining partial mastectomy with immediate breast reshaping using a combination of several flaps was successfully performed in a patient with early breast cancer.

Surgical treatment offering both cure and good cosmetic outcomes is important in patients with breast cancer. Mastectomy followed by breast reconstruction is performed with a combination of autologous tissue or implant and can be immediate or delayed in one stage or two stages, respectively. Breast surgeons and plastic surgeons should understand the characteristic indications for surgery and select the appropriate procedure for each patient. Oncoplastic breast surgery (OBS) at the time of breast-conserving surgery is classified into two main methods, volume replacement and volume displacement. It is necessary for clinicians to understand both the advantages and disadvantages of oncoplastic procedures. The problem of some OBS methods remaining ineligible for coverage by national health insurance in Japan remains unresolved, but OBS will become more important as a novel method offering a balance between cancer curability and excellent cosmetic results in the near future.

Apocrine papillary lesion (APL) is difficult to diagnose as benign or malignant. We experienced an APL remaining in the body for 22 years. We present a case of a 71-year-old woman who had undergone excisional biopsy 22 years previously at the first hospital that she visited. 1 year previously, she had undergone fine-needle aspiration cytology at a second hospital, and the lesion was diagnosed as potentially malignant. She underwent core-needle biopsy at a third hospital, but whether the lesion was benign or malignant could not be definitively diagnosed. We performed right mastectomy and sentinel lymph-node biopsy, because her tumor was suspected to be malignant based on imaging means, and malignancy could not be ruled out on either biopsy or cytology. The histopathological diagnosis was tiny foci of apocrine proliferative lesion with massive hemorrhagic necrosis and no tumor metastasis in two sentinel lymph nodes. Retrospectively, we compared all of the patient’s previous specimens with the present ones, and applied the recent pathological diagnostic criteria. Although the biopsy specimen excised 22 years ago suggested an encapsulated apocrine papillary carcinoma or a papilloma with apocrine ductal carcinoma in situ, neither infiltration nor metastasis has occurred. Furthermore, neither the pathological findings nor the clinical behavior has changed over time.

Recent studies have indicated that increased ribosomal activity contributes to cancer progression. Transcription termination factor, RNA polymerase I (TTF1) acts as a transcription factor for RNA polymerase I. However, the role which TTF1 plays in cancer progression still remains unknown. The present study aimed to determine whether TTF1 plays a critical role in the progression of human liver hepatocellular carcinoma (HCC). In the present study, quantitative real-time reverse transcription polymerase chain reaction was conducted to evaluate TTF1 mRNA expression in 60 HCC tissue samples in order to determine the clinicopathological significance of TTF1. To investigate whether the expression levels of TTF1 were associated known gene signatures which represented ribosomal activity, we applied gene set enrichment analysis (GSEA) to HCC cases in The Cancer Genome Atlas (TCGA) a. We also performed in vitro proliferation assays using TTF1‑overexpressing HCC cells. TTF1 expression was significantly higher in HCC tumor tissues than in adjacent liver tissues (P

Therapeutic mammoplasty (TM) for breast cancer is a widely practiced oncoplastic technique. Intraductal spread towards the nipple or the location of the cancerous lesion on the central breast may become a contraindication for breast-conserving surgery. We herein report the results of TM in such cases. Six patients underwent TM that combined partial mastectomy with free nipple-areola (NA) grafting. The nipple was removed together with the cancerous lesions, and the areola was preserved for NA reconstruction. The tumors were located in the lower quadrant (n = 1), the central area (n = 1), the upper-outer area (n = 2), and the upper-inner area (n = 2). The types of mammoplasty that were performed included: amputation (n = 1), inverted T mammoplasty (n = 3), and L mammoplasty (n = 2). With the exception of one patient, all patients underwent inverted T mammoplasty on the contralateral breast in order to achieve symmetry. The total surgical and plastic periods ranged from 155 to 235 min (mean 207 min) and 100 to 150 min (mean 121 min), respectively. Oncological safety and excellent cosmetic results were achieved. TM combining partial mastectomy with NA grafting was successfully performed in patients with early-stage cancer in all quadrant areas.

Hepatocellular carcinoma (HCC) is a poor-prognosis cancer due to its high rate of recurrence. microRNAs (miRNAs) are a class of small non-coding RNA molecules that affect crucial processes in cancer development. The objective of this study is to identify the role of miRNAs in patient bone marrow (BM) and explore the function of these molecules during HCC progression. We purified miRNAs from bone marrow cells of seven HCC patients, and divided them into three fractions by cell surface markers as follows: CD14(+) (macrophage), CD14(-)/CD45(+) (lymphocyte), and CD14(-)/CD45(-)/EpCAM(+) (epithelial cell). We employed microarray-based profiling to analyze miRNA expression in the bone marrow of patients with HCC. Differentially expressed miRNAs were significantly different between fractions from whole bone marrow, macrophages, and lymphocytes, and depended on stages in tumor progression. Differences in expression of miRNAs associated with cell proliferation also varied significantly between HCC patients with recurrence, multiple tumors, and advanced clinical stages. These results suggest that miRNA profiles in separated fractions of BM cells are associated with HCC progression.

RNA polymerase 1 transcription termination factor (TTF1) mediates the transcription of ribosomal RNA (rRNA). In the current study, we investigated the clinical and biological significance of the TTF1 gene in colorectal cancer (CRC). The expression of TTF1 messenger RNA (mRNA) in tumor and normal tissues from 136 patients with CRC was examined by quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR). We also performed in vitro cell proliferation and migration assays in TTF1-expressing CRC cells. The biological role of TTF1 in CRC was further elucidated using gene set enrichment analysis (GSEA) with CRC samples. TTF1 expression was significantly higher in tumor tissues than in corresponding normal tissues (p = 0.016). In clinicopathological analysis, the high-TTF1 expression group showed a higher incidence of liver metastasis and lymphatic invasion than the low-TTF1 expression group (p

MicroRNAs have roles in the regulation of the epithelial–mesenchymal transition (EMT). Findings have shown that miR-506 inhibits the expression of SNAI2 and that low expression of miR-506 is associated with poor prognoses in ovarian and breast cancers. This study investigated the role of miR-506 in survival and the EMT in patients with gastric cancer. In this study, miR-506 and SNAI2 mRNA levels were measured in 141 cases of gastric cancer by quantitative reverse transcription polymerase chain reaction, and the protein expressions of SNAI2 and E-cadherin in 39 cases were validated by immunohistochemical analysis. Next, the associations between their expression levels and clinicopathologic factors were evaluated. In addition, cell proliferation, migration, and luciferase activity of the 3′ untranslated region (UTR) of SNAI2 were analyzed using pre-miR-506 precursor in two human gastric cancer cell lines. Low expression of miR-506 was significantly correlated with poor overall survival in both the univariate analysis (P = 0.016) and the multivariate analysis (P

Background Predictive biomarkers for the recurrence of hepatocellular carcinoma (HCC) have great benefit in the selection of treatment options, including liver transplantation (LT), for HCC. The purpose of this study was to identify specific microRNAs (miRs) in exosomes from the serum of patients with recurrent HCC and to validate these molecules as novel biomarkers for HCC recurrence. Methods We employed microarray-based expression profiling of miRs derived from exosomes in the serum of HCC patients to identify a biomarker that distinguishes between patients with and without HCC recurrence after LT. This was followed by the validation in a separate cohort of 59 HCC patients who underwent living related LT. The functions and potential gene targets of the recurrence-specific miRs were analysed using a database, clinical samples and HCC cell lines. Results We found that miR-718 showed significantly different expression in the serum exosomes of HCC cases with recurrence after LT compared with those without recurrence. Decreased expression of miR-718 was associated with HCC tumour aggressiveness in the validated cohort series. We identified HOXB8 as a potential target gene of miR-718, and its upregulation was associated with poor prognosis. Conclusion Circulating miRs in serum exosomes have potential as novel biomarkers for predicting HCC recurrence.

Disseminated carcinomatosis of the bone marrow (DCBM) is characterized by diffuse infiltrative growth of tumor cells in the bone marrow and is associated with systemic hematological disorders. Bone marrow metastases from breast cancer are not rare, and they may lead to serious life-threatening conditions when there is an associated hematological disorder. Therefore, DCBM necessitates a definitive diagnosis and prompt systemic therapy. We herein present 4 such cases and a review of the previous relevant literature. Bone marrow biopsy is an effective method for diagnosing DCBM, and it may also be useful for selecting the optimal therapy. The malignant cells in the bone marrow biopsy specimens from all 4 patients were negative for progesterone receptor expression, and in 1 case, human epidermal growth factor receptor 2/neu expression was discordant between the primary tumor and the bone marrow metastases. Patients with DCBM often require granulocyte colony-stimulating factor and/or blood transfusions due to a DCBM-related hematological disorder. Although systemic chemotherapy for DCBM may temporarily exacerbate the need for hematological support, systemic chemotherapy may be effective for DCBM in breast cancer patients. In our experience, endocrine therapy has also been proven effective for DCBM. The aim of the present study was to review the clinical characteristics and the treatments used in 4 breast cancer patients with DCBM.

[This corrects the article DOI: 10.1371/journal.pgen.1005778.].

Intraoperative identification of the difficult-to-spot parathyroid gland is critical during surgery for thyroid and parathyroid disease. Recently, intrinsic fluorescence of the parathyroid gland was identified, and a new method was developed for intraoperative detection of the parathyroid with an original fluorescent detection apparatus. Here, we describe a method for intraoperative detection of the parathyroid using a ready-made photodynamic eye (PDE) system without any fluorescent dye or contrast agents. Seventeen patients who underwent surgical treatment for thyroid or parathyroid disease at Kagoshima University Hospital were enrolled in this study. Intrinsic fluorescence of various tissues was detected with the PDE system. Intraoperative in vivo and ex vivo intrinsic fluorescence of the parathyroid, thyroid, lymph nodes and fat tissues was measured and analyzed. The parathyroid gland had a significantly higher fluorescence intensity than the other tissues, including the thyroid glands, lymph nodes and fat tissues, and we could identify them during surgery using the fluorescence-guided method. Our method could be applicable for two intraoperative clinical procedures: ex vivo tissue identification of parathyroid tissue and in vivo identification of the location of the parathyroid gland, including ectopic glands. The PDE system may be an easy and highly feasible method to identify the parathyroid gland during surgery.