Breast Pseudoaneurysm in a Woman after Core Biopsy: Intravascular Glue Embolization.

Core needle biopsy of breast masses is a common procedure for tissue diagnosis of breast lesions. The incidence of complications is low, with pseudoaneurysm (PA) after core biopsy has been described in the literature, and the subsequent need for surgical management. Ultrasonography is the most common modality used for not only diagnosis but also treatment of a PA. Color Doppler images show a heterogeneous echoic lesion with whirling flow inside of the lesion. We describe a patient whose breast PA that developed after core needle biopsy was successfully treated with sonographically-guided intravascular glue embolization.

Comparison of Diagnostic Performance and Confidence between Contrast-Enhanced Computed Tomography Scan and Non-Contrast-Enhanced Computed Tomography Plus Abdomen Ultrasound for Hepatic Metastasis in Patients with Breast Cancer.

Background: The purpose of this study was to compare the performance between noncontrast-enhanced computed tomography (NECT) plus abdominal ultrasound (US) (NECT + US) with contrast-enhanced computed tomography (CECT) for the detection of hepatic metastasis in breast cancer patient with postsurgical follow-up. Methods: A total of 1470 patients without already diagnosed hepatic metastasis were included. All patients underwent US and multiphase CECT including the NECT. Independent reviewers analyzed images obtained in four settings, namely, abdominal US, NECT, NECT + US, and CECT and recorded liver metastases using a 5-grade scale of diagnostic confidence. Sensitivity, specificity (diagnostic performance), and area under the receiver operating characteristic curve (AUC, diagnostic confidence) were calculated. Interoperator agreement was calculated using the kappa test. Results: Reference standards revealed no metastases in 1108/1470 patients, and metastasis was detected in 362/1470 patients. Abdominal US (P < 0.01) and NECT (P = 0.01) significantly differed from CECT, but NECT + US did not significantly differ from CECT in terms of sensitivity (P = 0.09), specificity (P = 0.5), and AUC (P = 0.43). After an additional review of abdominal US, readers changed the diagnostic confidence scores of 106 metastatic lesions diagnosed using NECT. Interobserver agreements were good or very good in all four settings. Additional review of abdominal US with NECT allowed a change in the therapeutic plan of 108 patients. Conclusion: Abdominal US + NECT showed better diagnostic performance for the detection of hepatic metastases than did NECT alone; its diagnostic performance and confidence were similar to those of CECT.

The efficacy of oxidized regenerated cellulose (SurgiGuard®) in breast cancer patients who undergo total mastectomy with node surgery: A prospective randomized study in 94 patients.

BACKGROUND: Seromas frequently develop in patients who undergo total mastectomy with node surgery. We aimed to prospectively explore whether use of oxidized regenerated cellulose (ORC, SurgiGuard®) affects seroma formation after total mastectomy with node surgery (sentinel lymph node biopsy (SLNB) or axillary lymph node dissection (ALND)). MATERIALS AND METHODS: Ninety four breast cancer patients were enrolled in the study who underwent total mastectomy with ALND or SLNB. The patients were randomized into two groups, one treated with ORC plus closed suction drainage and the other with closed suction drainage alone. RESULTS: Mean drainage volume was slightly lower in the ORC group on postoperative day 1 (123 ± 54 vs 143 ± 104 ml), but was slightly higher at all other time points; however, these differences were not significant. Mean total drainage volume in patients treated with ORC plus drainage did not differ from that of patients treated with drainage alone (1134 ± 507 ml vs 1033 ± 643 ml, P = 0.486). CONCLUSIONS: Use of ORC (SurgiGuard®) did not significantly alter the risk of seroma formation.

Subsequent pregnancy and long-term safety after breast cancer: a retrospective analysis of Korean health insurance data.

PURPOSE: Long-term safety of pregnancy after breast cancer (BC) remains controversial, especially with respect to BC biological subtypes. METHODS: We analyzed a population-based retrospective cohort with BC from 2002 to 2017. Patient-level 1:1 matching was performed between pregnant and nonpregnant women. The study population was categorized into 6 biological subtypes based on the combination of prescribed therapies. Subanalyses were performed considering the time to pregnancy after BC diagnosis, systemic therapy, and pregnancy outcomes. RESULTS: We identified 544 matched women with BC, who were assigned to the pregnant (cases, n = 272) or nonpregnant group (controls, n = 272) of similar characteristics, adjusted for guaranteed bias. These patients were followed up for 10 years, or disease and mortality occurrence after the diagnosis of BC. Survival estimates were calculated. The actuarial 10-year overall survival (OS) rates were 97.4% and 91.9% for pregnant and nonpregnant patients, respectively. The pregnant group showed significantly better OS (adjusted hazard ratio [aHR], 0.29; 95% confidence interval [CI], 0.12-0.68; P = 0.005) and did not have a significantly inferior disease-free survival (aHR, 1.10; 95% CI, 0.61-1.99; P = 0.760). CONCLUSION: Consistent outcomes were observed in every subgroup analysis. Our observational data provides reassuring evidence on the long-term safety of pregnancy in young patients with BC regardless of the BC biological subtype.

A critical review of abdominopelvic computed tomography for the detection of asymptomatic metastasis in new and recurrent breast cancers.

AIM: Abdominopelvic computed tomography (APCT) is a commonly used staging investigation to detect asymptomatic metastasis in breast cancer including early breast cancer (EBC). This study aimed to assess the usefulness of APCT in breast cancers at each clinical stage. METHODS: Patients with new or recurrent invasive breast cancer between January 2009 and December 2014 were included in the study. All staging APCT results were reviewed to evaluate its yield and false positive rate (FPR) and how many investigations are needed to confirm indeterminate results. Odds ratios (ORs) for positive APCT results were calculated for possible risk factors for asymptomatic metastasis. RESULTS: Sixty-five asymptomatic metastases were detected from 1002 APCTs, giving an overall yield of 6.5%. The overall false-positive rate was 14.9 % due to 149 indeterminate findings that were found not to be metastases after further investigations or observation. Whereas the APCTs have a low yield of 3.1% in EBC, but advanced breast cancer and recurrent breast cancer have a high incidence of asymptomatic metastases (13.8% and 16.3%, respectively). The most common cause of indeterminate findings was small liver nodules, including liver cysts and liver hemangiomas. Human epidermal growth factor receptor2 (HER2) status and tumor stage are most significant predictors for positive results of staging APCT scans with high ORs (3.9 and 3.7, respectively). CONCLUSION: Staging APCT is associated with a high incidence of FPRs and low yield, especially among EBCs. It is desirable to choose this investigation more selectively according to HER2 status and tumor stage.

Diagnostic accuracy of non-contrast abdominopelvic computed tomography scans in follow-up of breast cancer patients.

OBJECTIVES: To evaluate the effectiveness of follow-up with non-enhanced CT (NECT) in patients with breast cancer. METHODS: The present retrospective study included 1396 patients with breast cancer. Group A included patients with no metastasis to evaluate the diagnostic performance of NECT in detecting newly developed metastasis. Group B included patients with known hepatic metastasis to evaluate the accuracy of NECT for the assessment of hepatic metastasis. RESULTS: Group A included 895 patients (mean age 52.8 years). Among them, 145 patients had 160 metastases. The per-patient sensitivities for diagnosing newly developed metastasis were 68.3 and 53.8% according to the two reviewers, while the per-lesion sensitivities were 89.4 and 85.0%. Sensitivities for bone metastasis were 98.9 and 95.9%, while sensitivities for hepatic metastasis were 73.7 and 68.4%. In group B, the accuracy of hepatic metastasis response evaluation according to the RECIST criteria was 70.8% for reviewer 1 and 63.8% for reviewer 2. CONCLUSIONS: NECT showed inadequate diagnostic performance in detecting newly developed metastasis and in evaluating the response of hepatic metastasis. However, NECT can be utilized as a follow-up modality in patients with decreased renal function or hypersensitivity to iodinated contrast media. ADVANCES IN KNOWLEDGE: The risk of side effects of contrast media should be considered as important when NECT can be utilized as a follow-up modality in decreased renal function patients.

An analysis of the outcomes of totally implantable access port implantation performed by surgical residents.

Purpose: This study aimed to investigate the clinical outcomes after totally implantable access port (TIAP) implantation performed by general surgery residents in patients with colorectal cancer. Methods: A total of 291 consecutive patients who underwent TIAP implantations were evaluated. The patients were divided into three groups: second-, third-, and fourth-grade residents. Results: The mean follow-up was 22.1 months (range, 1-87 months). The total times of operation, puncture, and cannulation decreased as the resident grade increased (P<0.001). Early complications significantly decreased with higher resident grades (P=0.039). The non-use of ultrasonography and non-use of C-arm were identified as independent risk factors for complications. Resident grades between second and third (P=0.005) and between second and fourth (P=0.041) were identified as independent risk factors for optimal tip position. Conclusion: TIAP implantation can be safely and effectively performed by residents. Low-grade residents were associated with early complications.

Inframammary Fold Incision Can Reduce Skin Flap Necrosis in Immediate Breast Reconstruction With Implant and Conjoined Fascial Flap.

BACKGROUND: Immediate breast reconstruction with implant (IBRI) can produce good aesthetic results after nipple-sparing mastectomy (NSM). Various surgical incisions can be used for NSM. The purpose of this study is to compare outcomes of using an IBRI with dual-coverage fascial flap after NSM with an inframammary fold (IMF) or a radial (Rd) incision. METHODS: We retrospectively reviewed the records of 88 women who underwent IBRI with dual-coverage fascial flap from March 2015 to June 2018. Inframammary fold incision was used in 19 patients (22 breasts) and Rd incision in 69 patients (75 breasts). In the dual-coverage method, acellular dermal matrix covered the inferomedial quadrant of the breast, and conjoined fascial flap covered the remaining inferolateral quadrant. Patient-reported satisfaction was assessed using the Breast-Q questionnaire, and plastic surgeons assessed aesthetic postoperative scores. RESULTS: Complications and reoperation rates of 2 incisions were as follows: skin flap necrosis rate showed significant difference between 2 groups (IMF, 0.0% [0/22]; Rd, 16.0% [12/75]; P < 0.05). The other complication rates, hematoma, seroma, infection, capsular contracture, and total reoperations showed no significant difference. Postoperative Breast-Q scores were higher in the IMF group (331.9 ± 10.1) than in the Rd group (311.4 ± 11.0; P < 0.05), indicating higher satisfactory rate in the IMF group than in the Rd group. Surgeon-reported scores for breast symmetry, contour, and scar appearance were also higher in the IMF group (P < 0.05). CONCLUSIONS: Immediate breast reconstruction with implant with dual-coverage fascial flap after NSM with IMF incision was associated with a lower rate of postoperative skin flap necrosis and improved patient satisfaction, compared with Rd incision. Inframammary fold incisions were associated with improved scar and breast appearance.

Poorly differentiated thyroid carcinoma: An institutional experience.

Purpose: The incidence of poorly differentiated thyroid carcinoma (PDTC) is extremely low among thyroid cancers and there is no standardized treatment guideline for it. In this study, we have analyzed PDTC patients and reviewed their clinicopathological features. Methods: Data of PDTC patients from our institution are collected through the electronic medical database. We analyzed them by several parameters such as basic demographics, presenting symptom, preoperative cytology results, associated pathology, surgical results, surgery type, and distant metastasis. Results: We collected 23 cases in our institution. Apart from two patients who were transferred to another hospital upon diagnosis, all 21 operated cases are analyzed. The parameters we studied were age, sex, presenting symptoms, distant metastasis and pathological features such as tumor size, associated pathology, predominant pattern and so on. We also provided descriptive analyses according to the type of presentation and treatment; patients with distant metastasis, juvenile cancer, and concurrent hyperthyroidism. Furthermore, we provided different cases in which the initial surgical plans differed. Conclusion: We present 21 cases of PDTC patients and clarify their clinicopathological features. Despite some limitations, this study may shed light for future research regarding treatment of PDTC patients.

Extent of lateral neck dissection for papillary thyroid microcarcinomas.

BACKGROUND: Papillary thyroid microcarcinomas (PTMCs) often demonstrate lateral lymph node (LN) metastasis. The purpose of this study was to assess whether the size of primary tumor should be considered in deciding lateral neck dissection extent. METHODS: We conducted a retrospective comparison of patients with PTMC and papillary thyroid carcinoma (PTC) larger than 1 cm who received lateral LN dissection from 2009 to 2015. RESULTS: PTMC group had more frequent metachronous metastasis, multifocality, less involvement of lower third thyroid, lower metastatic central LN counts and ratio, and lower metastatic total LN ratio. The two groups showed no difference in lateral LN metastatic pattern. Male and lymphovascular invasion were more often found in PTMCs with synchronous lateral LN metastatic events than metachronous presentations. CONCLUSIONS: Relying on the size of the tumor to determine lateral neck dissection extent could be unreliable, because there is no observed difference in lateral neck metastatic count and pattern between PTC and PTMCs.

Gene expression assay and Watson for Oncology for optimization of treatment in ER-positive, HER2-negative breast cancer.

BACKGROUND: Personalized treatment for cancer patients is a hot topic of debate, particularly the decision to initiate chemotherapy in patients with Estrogen receptor (ER)-positive, HER2-negative tumors in the early stages of breast cancer (BC). Owing to significant advancements in information technology (IT) and genomics, clinicians are increasingly attaining therapeutic goals rapidly and safely by effectively differentiating patient subsets that require chemotherapy. IBM Watson for Oncology (WFO) is a cognitive computing system employed by clinicians to provide evidence-based treatment options for cancer. WFO aids in clinical diagnosis, with claims that it may be superior in performance to human clinicians. The current study was based on the hypothesis that WFO alone cannot effectively determine whether or not chemotherapy is essential for the subset of ER-positive, HER2-negative BC patients. PATIENTS AND METHODS: From December 2015 to July 2017, 95 patients with ER-positive, HER2- negative BC subjected to treatment were retrospectively examined using WFO, and outputs compared to real clinical practice. Treatment options were suggested by WFO, and WFO recommendations calculated both with and without data from the gene expression assay (GEA). RESULTS: WFO without GEA was unable to determine the groups of patients that did not require chemotherapy. Concordant therapeutic recommendations between real clinical practice and WFO without GEA were obtained for 23.2% of the patient group. On the other hand, the results of WFO with GEA showed good clinical applicability. Sensitivity, specificity, positive predictive and negative predictive values of WFO with GEA were 100%, 80%, 61% and 100%, respectively. CONCLUSIONS: Our collective findings indicate that WFO without the gene expression assay has limited clinical utility.

Optimal combination of treatment modality to increase survival in patients with anaplastic thyroid carcinoma: A STROBE compliant retrospective study.

There is little consensus on the optimal treatment approach for newly diagnosed patients. The present study aims to provide additional evidence by evaluating a series of patients diagnosed with anaplastic thyroid carcinoma (ATC) and analyzing factors related to increased survival. This was a retrospective cohort report structured according to the Strengthening the Reporting of Observational studies in Epidemiology (STROBE) guideline. Demographics, chief complaint, history of prior thyroid cancer, stage at presentation, management modalities (surgery, chemotherapy, radiotherapy, or observation), completeness or resection, and survival period since initial diagnosis were reviewed for patients with documentation of histologic ATC diagnosis between 2003 and 2016. The median survival period for 34 patients (11 males, 23 females) was 93.5 days. Patients aged 70 or younger (111 days) tended to survive longer than those older 70 (88 days) (P = .081). Observation, surgery only, radiotherapy only, and chemo-radiotherapy after surgery group showed median survival of 88 days, 49 days (range 14-528), 61.5 days, and 225 days, respectively. There was also no significant difference in survival between the 10 (29.4%) stage IVb (225 days) and 23 (67.7%) IVc (88 days) patients (P = .242). The median survival of the R1 resection group was 514 days while that of the R2 group was 102 days (P = .338). There were no significant difference between patients with the de novo ATC (112 days) and patients with papillary thyroid carcinoma origin ATC (99 days) (P = .297). Results from our series of 34 patients with ATC show that more intense combination of surgery and chemo-radiotherapy tends to secure a longer survival period. Therefore we recommend a multi-modality approach after a comprehensive consultation with the patient.

Comparison of Outcomes of Hybrid and Surgical Correction for De Novo Arteriovenous Graft Occlusion.

PURPOSE: This study aimed to compare surgical revisions and balloon angioplasty after surgical thrombectomy on thrombosed dialysis access as a first event. MATERIALS AND METHODS: Records of patients undergoing creation of arteriovenous grafts (AVGs) at the Gachon University Gil Medical Center between March 2008 and February 2016 were reviewed. Among them, patients who underwent treatment on first-time thrombotic occlusion after AVG creation were identified. Outcomes were primary, primary-assisted, and secondary patency. The patency was generated using the Kaplan-Meier method, and patency rates were compared by log-rank test. RESULTS: A total of 59 de novo interventions (n=26, hybrid interventions; n=33, surgical revisions) for occlusive AVGs were identified. The estimated 1-year primary patency rates were 47% and 30% in the surgery and hybrid groups, respectively. The estimated primary patency rates were not different between the two groups (log-rank test, P=0.73). The Kaplan-Meier estimates of 6 and 12 months for primary-assisted patency rates were 68% and 57% in the surgery group and 56% and 56% in the hybrid group. The Kaplan-Meier estimates of 12 and 24 months secondary patency rates were 90% and 71% in the surgery group and 79% and 62% in the hybrid group. There were no differences in the estimated primary-assisted and secondary patency rates between the two groups. CONCLUSION: Our results showed no significant difference between the two groups in terms of primary patency (P=0.73), primary-assisted patency (P=0.85), and secondary patency (P=0.78). However, percutaneous transluminal angioplasty can give more therapeutic options for both surgeons and patients.

Prognostically Distinctive Subgroup in Pathologic N3 Breast Cancer.

PURPOSE: The aim of this retrospective study was to investigate whether there are prognostically different subgroups among patients with pathologic N3 (pN3) breast cancer. METHODS: The records of 220 patients who underwent surgery for pN3 breast cancer from January 2006 to September 2012 were reviewed. All patients received adjuvant therapy according to standard protocols. The primary outcome was disease-free survival (DFS). RESULTS: Patients were followed for a median time of 68.3 months after their primary surgery (range, 10-122 months), during which time 75 patients (34.1%) had developed disease recurrence and 48 patients (21.8%) had died. The DFS and overall survival were 67.8% and 86.1%, respectively, at 5 years. Multiple logistic regression analysis showed that young age (<35 years, p=0.009), high serum neutrophil/lymphocyte ratio (>3.0) (p=0.020), high nodal ratio (number of metastatic lymph nodes divided by number of removed nodes) (>0.65) (p=0.062), and molecular phenotype (p=0.012) were significantly associated with tumor recurrence. Tumor biological subtype was the most significant predictor of recurrence. The 5-year DFS rates in patients with hormone receptor (HR) positive and human epidermal growth factor receptor 2 (HER2) negative, HR+HER2+, HR-HER2+, and triple negative subtypes were 82%, 63%, 58%, and 37%, respectively. CONCLUSION: Clinical outcomes of patients with extensive nodal metastasis were heterogeneous in terms of prognosis. Tumor biological subtype was the most important prognostic factor for pN3 disease. The prognosis of patients with HR+HER2- subtype in pN3 breast cancer was similar to that of patients with stage II breast cancer.

Changing patterns of microcalcification on screening mammography for prediction of breast cancer.

BACKGROUND: The presence of microcalcification on mammography is one of the earliest signs in breast cancer detection. However, it is difficult to distinguish malignant calcifications from benign calcifications. The aim of this study is to evaluate correlation between changing patterns of microcalcification on screening mammography and malignant breast lesions. METHODS: Medical records and diagnostic images of 67 women who had previously undergone at least two digital mammograms at least 6 months apart and underwent mammography-guided needle localization and surgical excision between 2011 and 2013 were retrospectively reviewed and analyzed. RESULTS: Breast cancer was detected in the surgical specimens of 20 patients (29.9 %). Annual change of extent of microcalcification on mammography showed statistically significant correlation with pathologic outcome (P = 0.023). The changing pattern of new appearance or increased extent of microcalcification on mammography had positive predictive value of 54.8 % for breast cancer, and it was a statistically significant predictor for breast cancer (P = 0.012). Shape or number change of microcalcification without increased extent had less accurate predictive value for breast cancer, particularly in women younger than 50 years (P < 0.001). CONCLUSIONS: This study showed that the pattern of increased extent of microcalcification on screening mammography was a significant predictor for breast cancer. We suggest that mammography-guided needle localization and surgical excision should be considered when increased extent of microcalcification is observed on screening mammography and closed follow-up without pathologic confirmation can be permitted if absence of extension of microcalcification was confirmed in women younger than 50 years.

Ki-67 as a predictor of response to neoadjuvant chemotherapy in breast cancer patients.

PURPOSE: The objectives of this study were to assess the potential value of Ki-67 in predicting response to neoadjuvant chemotherapy in breast cancer patients and to suggest a reasonable cutoff value for classifying Ki-67 expression. METHODS: This study included 74 breast cancer patients who underwent surgery after anthracycline-based neoadjuvant chemotherapy between 2007 and 2012. We analyzed the clinical and immunohistochemical characteristics using core biopsy specimens obtained before neoadjuvant chemotherapy to determine their correlations with the response to chemotherapy. RESULTS: A clinical complete response was observed in 6 patients (8.1%); a clinical partial response, in 44 patients (59.5%); and clinical stable disease, in 24 patients (32.4%). A pathologic complete response (pCR) was observed in 10 patients (13.5%). In univariate analysis, estrogen receptor (ER) negativity (p=0.031), human epidermal growth factor receptor 2 (HER2) positivity (p=0.040), and high Ki-67 expression (p=0.036) were predictive factors for a pCR. In multivariate analysis, Ki-67 was the only independent predictor of a pCR (p=0.049). The analysis of Ki-67 values revealed that 25% was a reasonable cutoff value for predicting the response to chemotherapy. In subgroup analysis, a higher Ki-67 value (≥25%) was a significant predictive factor for the response to neoadjuvant chemotherapy, especially in ER-negative and HER2-positive breast cancer patients. CONCLUSION: Ki-67 expression in breast cancer tissue may be an effective factor for predicting the response to neoadjuvant chemotherapy. We suggest that a 25% level of Ki-67 expression is a reasonable cutoff value for predicting a response to chemotherapy. Moreover, Ki-67 is a useful predictive factor for pCR, especially in patients with ER-negative and HER2-positive breast cancer.

Intraductal administration of a polymeric nanoparticle formulation of curcumin (NanoCurc) significantly attenuates incidence of mammary tumors in a rodent chemical carcinogenesis model: Implications for breast cancer chemoprevention in at-risk populations.

Multiple lines of evidence support a role for curcumin in cancer chemoprevention. Nonetheless, despite its reported efficacy and safety profile, clinical translation of curcumin has been hampered by low oral bioavailability, requiring infeasible 'mega' doses for achieving detectable tissue levels. We have engineered a polymeric nanoparticle encapsulated formulation of curcumin (NanoCurc) to harness its full therapeutic potential. In the current study, we assessed the chemoprevention efficacy of NanoCurc administered via direct intraductal (i.duc) injection in a chemical carcinogen-induced rodent mammary cancer model. Specifically, Sprague-Dawley rats exposed to systemic N-methyl-N-nitrosourea were randomized to receive either oral free curcumin at a previously reported 'mega' dose (200mg/kg) or by direct i.duc injection of free curcumin or NanoCurc, respectively, each delivering 168 µg equivalent of curcumin per rodent teat (a ~20-fold lower dose per animal compared to oral administration). All three chemoprevention modalities resulted in significantly lower mammary tumor incidence compared with control rats; however, there was no significant difference in cancer incidence between the oral dosing and either i.duc arms. On the other hand, mean tumor size, was significantly smaller in the i.duc NanoCurc cohort compared with i.duc free curcumin (P < 0.0001), suggesting the possibility of better resectability for 'breakthrough' cancers. Reduction in cancer incidence was associated with significant decrease in nuclear factor -κB activation in the NanoCurc treated mammary epithelium explants, compared to either control or oral curcumin-administered rats. Our studies confirm the potential for i.duc NanoCurc as an alternative to the oral route for breast cancer chemoprevention in high-risk cohorts.

Intraductally administered pegylated liposomal doxorubicin reduces mammary stem cell function in the mammary gland but in the long term, induces malignant tumors.

Previously, we have shown that the intraductal (i.duc) administration of pegylated liposomal doxorubicin (PLD) to Her2/neu transgenic mice is associated with mammary tumor regression and prevention. Exploring the mechanism underlying the protection afforded by PLD, we studied: the effects of i.duc PLD-treatment with a subsequent pregnancy on outgrowth of tumors in Her2/neu mice; whether the i.duc PLD antitumor effect was mediated partially through changes in normal mammary stem cells (MaSCs); and the long-term safety of i.duc PLD into the normal mouse mammary gland. Her2/neu mice were treated with two i.duc injections of PLD given four weeks apart; pregnancy was induced and mice were followed up for changes in physiology, and tumor formation. We found that all pups born to i.duc PLD-treated Her2/neu mice died without weight gain within 7 days after birth. Despite an additional pregnancy, compared to vehicle control PLD-treated Her2/neu mice had a significantly longer latency and lower frequency of tumor development. Mammary epithelial cells isolated from untreated and i.duc PLD-treated 6-8 months-old multiparous FVB/N mice were analyzed for their repopulating ability in mammary fat pads of naïve recipients. Mice were also monitored for abnormalities in mammary gland morphology and function, including tumor formation. PLD-treated FVB/N mice displayed histomorphologic changes and a significant reduction in the outgrowth potential of cells from the mammary glands. Thus, i.duc PLD administration altered the mammary gland structurally and functionally by reducing the MaSC population, which could compromise milk production. Followed long term, i.duc PLD-treated FVB/N mice developed malignant mammary tumors, confirming similar published findings on doxorubicin injected into the mammary gland of rats. Unless there are fundamental species differences in PLD metabolism in rodents and humans, this finding seriously limits the consideration of i.duc PLD use in the clinic for treatment or prevention of breast cancer.

Induced pluripotent stem cells and personalized medicine: current progress and future perspectives.

Generation of induced pluripotent stem cells (iPSCs) has revolutionized the field of regenerative medicine by providing researchers with a unique tool to derive disease-specific stem cells for study. iPSCs can self-renew and can differentiate into many cell types, offering a potentially unlimited source of cells for targeted differentiation into somatic effector cells. Hence, iPSCs are likely to be invaluable for therapeutic applications and disease-related research. In this review, we summarize the recent progress of iPSC generation that has been made with an emphasis on both basic and clinical applications including disease modeling, drug toxicity screening/drug discovery and cell replacement therapy.

Applications of patient-specific induced pluripotent stem cells; focused on disease modeling, drug screening and therapeutic potentials for liver disease.

The recent advances in the induced pluripotent stem cell (iPSC) research have significantly changed our perspectives on regenerative medicine by providing researchers with a unique tool to derive disease-specific stem cells for study. In this review, we describe the human iPSC generation from developmentally diverse origins (i.e. endoderm-, mesoderm-, and ectoderm- tissue derived human iPSCs) and multistage hepatic differentiation protocols, and discuss both basic and clinical applications of these cells including disease modeling, drug toxicity screening/drug discovery, gene therapy and cell replacement therapy.