Showing papers on "Surgical oncology published in 2014"

Sentinel Lymph Node Biopsy for Patients With Early-Stage Breast Cancer: American Society of Clinical Oncology Clinical Practice Guideline Update

Abstract: Purpose To provide evidence-based recommendations to practicing oncologists, surgeons, and radiation therapy clinicians to update the 2005 clinical practice guideline on the use of sentinel node biopsy (SNB) for patients with early-stage breast cancer. Methods The American Society of Clinical Oncology convened an Update Committee of experts in medical oncology, pathology, radiation oncology, surgical oncology, guideline implementation, and advocacy. A systematic review of the literature was conducted from February 2004 to January 2013 in Medline. Guideline recommendations were based on the review of the evidence by Update Committee. Results This guideline update reflects changes in practice since the 2005 guideline. Nine randomized clinical trials (RCTs) met systematic review criteria for clinical questions 1 and 2; 13 cohort studies informed clinical question 3. Recommendations Women without sentinel lymph node (SLN) metastases should not receive axillary lymph node dissection (ALND). Women with one to t...

Society of surgical oncology-American Society for Radiation Oncology consensus guideline on margins for breast-conserving surgery with whole-breast irradiation in stages i and II invasive breast cancer

Abstract: Purpose Controversy exists regarding the optimal margin width in breast-conserving surgery for invasive breast cancer.

Society of Surgical Oncology–American Society for Radiation Oncology Consensus Guideline on Margins for Breast-Conserving Surgery With Whole-Breast Irradiation in Stages I and II Invasive Breast Cancer

Abstract: Purpose Controversy exists regarding the optimal margin width in breast-conserving surgery for invasive breast cancer. Methods A multidisciplinary consensus panel used a meta-analysis of margin width and ipsilateral breast tumor recurrence (IBTR) from a systematic review of 33 studies including 28,162 patients as the primary evidence base for consensus. Results Positive margins (ink on invasive carcinoma or ductal carcinoma in situ) are associated with a two-fold increase in the risk of IBTR compared with negative margins. This increased risk is not mitigated by favorable biology, endocrine therapy, or a radiation boost. More widely clear margins do not significantly decrease the rate of IBTR compared with no ink on tumor. There is no evidence that more widely clear margins reduce IBTR for young patients or for those with unfavorable biology, lobular cancers, or cancers with an extensive intraductal component. Conclusion The use of no ink on tumor as the standard for an adequate margin in invasive cancer ...

Clinical significance of serum tumor markers for gastric cancer: a systematic review of literature by the Task Force of the Japanese Gastric Cancer Association

Abstract: The aim of this review was to evaluate the clinical significance of serum tumor markers, particularly CEA, CA19-9, and CA72-4, in patients with gastric cancer. A systematic literature search was performed using PubMed/MEDLINE with the keywords “gastric cancer” and “tumor marker,” to select 4,925 relevant reports published before the end of November 2012. A total of 187 publications contained data for CEA and CA19-9, and 19 publications contained data related to all three tumor markers. The positive rates were 21.1 % for CEA, 27.8 % for CA19-9, and 30.0 % for CA72-4. These three markers were significantly associated with tumor stage and patient survival. Serum markers are not useful for early cancer, but they are useful for detecting recurrence and distant metastasis, predicting patient survival, and monitoring after surgery. Tumor marker monitoring may be useful for patients after surgery because the positive conversion of tumor markers usually occurs 2–3 months before imaging abnormalities. Among other tumor markers, alpha-fetoprotein (AFP) is useful for detecting and predicting liver metastases. Moreover, CA125 and sialyl Tn antigens (STN) are useful for detecting peritoneal metastases. Although no prospective trial has yet been completed to evaluate the clinical significance of these serum markers, this literature survey suggests that combinations of CEA, CA19-9, and CA72-4 are the most effective ways for staging before surgery or chemotherapy. In particular, monitoring tumor markers that were elevated before surgery or chemotherapy could be useful for detection of recurrence or evaluation of the response.

Decreased expression of long noncoding RNA GAS5 indicates a poor prognosis and promotes cell proliferation in gastric cancer.

Abstract: Gastric cancer is the second leading cause of cancer death and remains a major clinical challenge due to poor prognosis and limited treatment options. Long noncoding RNAs (lncRNAs) have emerged recently as major players in tumor biology and may be used for cancer diagnosis, prognosis, and potential therapeutic targets. Although downregulation of lncRNA GAS5 (Growth Arrest-Specific Transcript) in several cancers has been studied, its role in gastric cancer remains unknown. Our studies were designed to investigate the expression, biological role and clinical significance of GAS5 in gastric cancer. Expression of GAS5 was analyzed in 89 gastric cancer tissues and five gastric cancer cell lines by quantitative reverse-transcription polymerase chain reaction (qRT-PCR). Over-expression and RNA interference (RNAi) approaches were used to investigate the biological functions of GAS5. The effect of GAS5 on proliferation was evaluated by MTT and colony formation assays, and cell apoptosis was evaluated by hochest stainning. Gastric cancer cells transfected with pCDNA3.1 -GAS5 were injected into nude mice to study the effect of GAS5 on tumorigenesis in vivo. Protein levels of GAS5 targets were determined by western blot analysis. Differences between groups were tested for significance using Student’s t-test (two-tailed). We found that GAS5 expression was markedly downregulated in gastric cancer tissues, and associated with larger tumor size and advanced pathologic stage. Patients with low GAS5 expression level had poorer disease-free survival (DFS; P = 0.001) and overall survival (OS; P < 0.001) than those with high GAS5 expression. Further multivariable Cox regression analysis suggested that decreased GAS5 was an independent prognostic indicator for this disease (P = 0.006, HR = 0.412; 95%CI = 2.218–0.766). Moreover, ectopic expression of GAS5 was demonstrated to decrease gastric cancer cell proliferation and induce apoptosis in vitro and in vivo, while downregulation of endogenous GAS5 could promote cell proliferation. Finally, we found that GAS5 could influence gastric cancer cells proliferation, partly via regulating E2F1 and P21 expression. Our study presents that GAS5 is significantly downregulated in gastric cancer tissues and may represent a new marker of poor prognosis and a potential therapeutic target for gastric cancer intervention.

uPA and PAI-1 as biomarkers in breast cancer: validated for clinical use in level-of-evidence-1 studies.

Abstract: Urokinase plasminogen activator (uPA) is an extracellular matrix-degrading protease involved in cancer invasion and metastasis, interacting with plasminogen activator inhibitor-1 (PAI-1), which was originally identified as a blood-derived endogenous fast-acting inhibitor of uPA. At concentrations found in tumor tissue, however, both PAI-1 and uPA promote tumor progression and metastasis. Consistent with the causative role of uPA and PAI-1 in cancer dissemination, several retrospective and prospective studies have shown that elevated levels of uPA and PAI-1 in breast tumor tissue are statistically independent and potent predictors of poor patient outcome, including adverse outcome in the subset of breast cancer patients with lymph node-negative disease. In addition to being prognostic, high levels of uPA and PAI-1 have been shown to predict benefit from adjuvant chemotherapy in patients with early breast cancer. The unique clinical utility of uPA/PAI-1 as prognostic biomarkers in lymph node-negative breast cancer has been confirmed in two independent level-of-evidence-1 studies (that is, in a randomized prospective clinical trial in which the biomarker evaluation was the primary purpose of the trial and in a pooled analysis of individual data from retrospective and prospective studies). Thus, uPA and PAI-1 are among the best validated prognostic biomarkers currently available for lymph node-negative breast cancer, their main utility being the identification of lymph node-negative patients who have HER-2-negative tumors and who can be safely spared the toxicity and costs of adjuvant chemotherapy. Recently, a phase II clinical trial using the low-molecular-weight uPA inhibitor WX-671 reported activity in metastatic breast cancer.

Margins for Breast-Conserving Surgery With Whole-Breast Irradiation in Stage I and II Invasive Breast Cancer: American Society of Clinical Oncology Endorsement of the Society of Surgical Oncology/American Society for Radiation Oncology Consensus Guideline

Abstract: Purpose The Society of Surgical Oncology (SSO)/American Society for Radiation Oncology (ASTRO) guideline on surgical margins for breast-conserving surgery with whole-breast irradiation in stage I and II invasive breast cancer was considered for endorsement. Methods The American Society of Clinical Oncology (ASCO) has a policy and set of procedures for endorsing practice guidelines developed by other organizations. ASCO staff reviewed the SSO/ASTRO guideline for developmental rigor; an ASCO ad hoc review panel of experts reviewed the guideline content. Results The ASCO ad hoc guideline review panel concurred that the recommendations are clear, thorough, and based on the most relevant scientific evidence in this content area and that they present options acceptable to patients. According to the SSO/ASTRO guideline, the use of no ink on tumor (ie, no cancer cells adjacent to any inked edge/surface of specimen) as the standard for an adequate margin in invasive cancer in the era of multidisciplinary therapy i...

MMP-9 expression varies according to molecular subtypes of breast cancer

Abstract: In 2014, breast cancer remains a major cause of mortality worldwide mostly due to tumor relapse and metastasis. There is currently a great interest in identifying cancer biomarkers and signalling pathways mechanistically related to breast cancer progression. Matrix metalloproteinase-9 (MMP-9) is a member of matrix degrading enzymes involved in cancer development, invasion and metastasis. Our objective was to investigate MMP-9 expression in normal human breast tissue and to compare it to that of breast cancer of various histological grades and molecular subtypes. We also sought to correlate MMP-9 expression with the incidence of metastasis, survival rates and relapse in breast cancer patients. MMP-9 was first studied using in silico analysis on available DNA microarray and RNA sequencing data of human breast cancer tissues and human breast cancer cell lines. We next ascertained MMP-9 expression in both normal breast tissue and in human breast carcinoma tissue microarrays. Significant increase in MMP-9 expression was found in breast cancer cells where compared to normal breast tissue. A positive correlation could also be established between elevated levels of MMP-9 and breast cancer of high histological grade. Furthermore, our results indicate that not only MMP-9 is differentially expressed between each molecular subset but also, more importantly MMP-9 overexpression revealed itself as a startling feature of triple-negative and HER2-positive breast cancers. Lastly, the clinical relevance of MMP-9 overexpression is strongly supported by its significant association with a higher incidence of metastasis and relapse. Differential expression of MMP-9 reflects the extent of cellular differentiation in breast cancer cells and is closely related to the most aggressive subtypes of breast cancer. Hence, MMP-9 is a promising prognostic biomarker of high-grade breast cancer. In our opinion, MMP-9 expression could help segregate subsets of aggressive breast cancer into clinically meaningful subtypes.

Impact of extent of surgery on survival in patients with small nonfunctional pancreatic neuroendocrine tumors in the United States.

Abstract: Background Nonfunctional pancreatic neuroendocrine tumors (PNETs) ≤2 cm have uncertain malignant potential, and optimal treatment remains unclear. Objectives of this study were to better understand their malignant potential, determine whether extent of surgery or lymph node dissection is associated with overall survival (OS), and identify other factors associated with OS.

High false-negative proportion of intraoperative histological examination as a serious problem for clinical application of sentinel node biopsy for early gastric cancer: final results of the Japan Clinical Oncology Group multicenter trial JCOG0302

Abstract: Background To evaluate the feasibility and accuracy of diagnosis using sentinel node (SN) biopsy in T1 gastric cancer, a multicenter trial was conducted by the Japan Clinical Oncology Group (JCOG).

Management of colorectal cancer presenting with synchronous liver metastases

Abstract: Up to a fifth of patients with colorectal cancer (CRC) present with synchronous hepatic metastases. In patients with CRC who present without intestinal obstruction or perforation and in whom comprehensive whole-body imaging confirms the absence of extrahepatic disease, evidence indicates a state of equipoise between several different management pathways, none of which has demonstrated superiority. Neoadjuvant systemic chemotherapy is advocated by current guidelines, but must be integrated with surgical management in order to remove the primary tumour and liver metastatic burden. Surgery for CRC with synchronous liver metastases can take a number of forms: the 'classic' approach, involving initial colorectal resection, interval chemotherapy and liver resection as the final step; simultaneous removal of the liver and bowel tumours with neoadjuvant or adjuvant chemotherapy; or a 'liver-first' approach (before or after systemic chemotherapy) with removal of the colorectal tumour as the final procedure. In patients with rectal primary tumours, the liver-first approach can potentially avoid rectal surgery in patients with a complete response to chemoradiotherapy. We overview the importance of precise nomenclature, the influence of clinical presentation on treatment options, and the need for accurate, up-to-date surgical terminology, staging tests and contemporary management options in CRC and synchronous hepatic metastatic disease, with an emphasis on multidisciplinary care.

Metabolic characterization of triple negative breast cancer

Abstract: The aims of this study were to characterize the metabolite profiles of triple negative breast cancer (TNBC) and to investigate the metabolite profiles associated with human epidermal growth factor receptor-2/neu (HER-2) overexpression using ex vivo high resolution magic angle spinning magnetic resonance spectroscopy (HR MAS MRS). Metabolic alterations caused by the different estrogen receptor (ER), progesterone receptor (PgR) and HER-2 receptor statuses were also examined. To investigate the metabolic differences between two distinct receptor groups, TNBC tumors were compared to tumors with ERpos/PgRpos/HER-2pos status which for the sake of simplicity is called triple positive breast cancer (TPBC). The study included 75 breast cancer patients without known distant metastases. HR MAS MRS was performed for identification and quantification of the metabolite content in the tumors. Multivariate partial least squares discriminant analysis (PLS-DA) modeling and relative metabolite quantification were used to analyze the MR data. Choline levels were found to be higher in TNBC compared to TPBC tumors, possibly related to cell proliferation and oncogenic signaling. In addition, TNBC tumors contain a lower level of Glutamine and a higher level of Glutamate compared to TPBC tumors, which indicate an increase in glutaminolysis metabolism. The development of glutamine dependent cell growth or “Glutamine addiction” has been suggested as a new therapeutic target in cancer. Our results show that the metabolite profiles associated with HER-2 overexpression may affect the metabolic characterization of TNBC. High Glycine levels were found in HER-2pos tumors, which support Glycine as potential marker for tumor aggressiveness. Metabolic alterations caused by the individual and combined receptors involved in breast cancer progression can provide a better understanding of the biochemical changes underlying the different breast cancer subtypes. Studies are needed to validate the potential of metabolic markers as targets for personalized treatment of breast cancer subtypes.

The Emerging Role of Neutrophil to Lymphocyte Ratio in Determining Colorectal Cancer Treatment Outcomes: A Systematic Review and Meta-Analysis

Abstract: Background There is growing evidence suggesting that the neutrophil to lymphocyte ratio (NLR) can act as an independent predictor of long-term outcomes in patients undergoing treatment for colorectal cancer (CRC). This study aims to systematically review the role of NLR in predicting survival for patients with CRC undergoing treatments, and to evaluate its utility within a CRC surveillance program.

Clinicopathological characteristics and prognosis of signet ring cell carcinoma of the stomach.

Abstract: Background Signet ring cell carcinoma (SRC) of the stomach is a histological type based on microscopic characteristics. Although the distinctive clinicopathological features of SRC have been reported, results are inconsistent and survival outcomes are uncertain.

The hunting of the src

Abstract: Peyton Rous beschrieb 1911 das Rous-Sarcoma-Virus (RSV) und vermutete, dass es ein Sarkom in Hühnerzellen „übertragen“ kann. In den 1960er-Jahren fanden Forscher in diesem Virus die Tyrosinkinase Src bzw. das erste retrovirale Onkogen, das v-src-Gen. Doch woher hat RSV ein Gen, das es gar nicht zur eigenen Replikation benötigt, das aber unkontrollierte Zellteilung stimuliert? Auf der „Jagd“ nach dem Ursprung des src-Gens stellte sich in den folgenden Jahren heraus, dass es als normales Gen, genannt c-src, in allen Vertebraten existiert. Wahrscheinlich hatte RSV ein mutiertes c-src aus einer Krebszelle in das eigene Genom integriert und trug damit den Krebs weiter. C-src, der Vorläufer des krebsverursachenden Gens, war also ein Gen aus einer normalen Zelle – das erste Protoonkogen. Doris Berger Für die Forschungsarbeit zum src wurde 1989 der Nobelpreis für Physiologie oder Medizin vergeben. Wer hat ihn erhalten?

Current Paradigms for Metastatic Spinal Disease: An Evidence-Based Review

Abstract: Management of metastatic spine disease is quite complex. Advances in research have allowed surgeons and physicians to better provide chemotherapeutic agents that have proven more efficacious. Additionally, the advancement of surgical techniques and radiosurgical implementation has altered drastically the treatment paradigm for metastatic spinal disease. Nevertheless, the physician–patient relationship, including extensive discussion with the neurosurgeon, medicine team, oncologists, radiation oncologists, and psychologists, are all critical in the evaluation process and in delivering the best possible care to our patients. The future remains bright for continued improvement in the surgical and nonsurgical management of our patients with metastatic spine disease. We include an evidence-based review of decision making strategies when attempting to determine most efficacious treatment options. Surgical treatments discussed include conventional debulking versus en bloc resection, conventional RT, and radiosurgical techniques, and minimally invasive approaches toward treating metastatic spinal disease. Surgical oncology is a diverse field in medicine and has undergone a significant paradigm shift over the past few decades. This shift in both medical and surgical management of patients with primarily metastatic tumors has largely been due to the more complete understanding of tumor biology as well as due to advances in surgical approaches and instrumentation. Furthermore, radiation oncology has seen significant advances with stereotactic radiosurgery and intensity-modulated radiation therapy contributing to a decline in surgical treatment of metastatic spinal disease. We analyze the entire spectrum of treating patients with metastatic spinal disease, from methods of diagnosis to the variety of treatment options available in the published literature.

Surgical resection of hepatic metastasis from gastric cancer: a review and new recommendation in the Japanese gastric cancer treatment guidelines

Abstract: Liver metastases from gastric cancer are rarely indicated for surgery because they are often diagnosed as multiple nodules occupying both lobes and coexist with extrahepatic disease. A literature search identified no clinical trials on hepatectomy for this disease; only retrospective studies of a relatively small number of cases collected over more than a decade, mostly from a single institution, were found. Five-year survival rates from these reports ranged from 0 % to 37 %, and long-term survivors were observed among carefully selected case series. The most commonly reported prognostic factor was the number of metastatic nodules, and patients with a solitary metastasis tended to have superior outcome. Patients diagnosed to have a small number of metastatic nodules by modern imaging tools could be indicated for surgery. Because both intrahepatic and extrahepatic recurrences are common, patients are likely to benefit from perioperative adjuvant chemotherapy, although it is not possible at this time to specify which regimen is the most appropriate.

Genomic patterns resembling BRCA1- and BRCA2-mutated breast cancers predict benefit of intensified carboplatin-based chemotherapy

Abstract: Introduction: BRCA-mutated breast cancer cells lack the DNA-repair mechanism homologous recombination that is required for error-free DNA double-strand break (DSB) repair. Homologous recombination deficiency (HRD) may cause hypersensitivity to DNA DSB-inducing agents, such as bifunctional alkylating agents and platinum salts. HRD can be caused byBRCA mutations, and by other mechanisms. To identify HRD, studies have focused on triple-negative (TN) breast cancers as these resemble BRCA1-mutated breast cancer closely and might also share this hypersensitivity. However, ways to identify HRD in non-BRCA-mutated, estrogen receptor (ER)-positive breast cancers have remained elusive. The current study provides evidence that genomic patterns resembling BRCA1- or BRCA2-mutated breast cancers can identify breast cancer patients with TN as well as ER-positive, HER2-negative tumors that are sensitive to intensified, DSB-inducing chemotherapy. Methods: Array comparative genomic hybridization (aCGH) was used to classify breast cancers. Patients with tumors with similar aCGH patterns as BRCA1 -a nd/orBRCA2-mutated breast cancers were defined as having a BRCA-like CGH status, others as non-BCRA-like CGH . Stage-III patients (n = 249) had participated in a randomized controlled trial of adjuvant high-dose (HD) cyclophosphamide-thiotepa-carboplatin (CTC) versus 5-fluorouracil-epirubicin-cyclophosphamide (FE90C) chemotherapy. Results: Among patients with BRCA-like CGH tumors (81/249, 32%), a significant benefit of HD-CTC compared to FE90C was observed regarding overall survival (adjusted hazard ratio 0.19, 95% CI: 0.08 to 0.48) that was not seen for patients with non-BRCA-like CGH tumors (adjusted hazard ratio 0.90, 95% CI: 0.53 to 1.54) (P = 0.004). Half of all BRCA-like CGH tumors were ER-positive. Conclusions: Distinct aCGH patterns differentiated between HER2-negative patients with a markedly improved outcome after adjuvant treatment with an intensified DNA-DSB-inducing regimen (BRCA-like CGH patients) and those without benefit (non-BRCA-like CGH patients).

ALDH1A1 expression correlates with clinicopathologic features and poor prognosis of breast cancer patients: a systematic review and meta-analysis

Abstract: Aldehyde dehydrogenase 1 family member A1 (ALDH1A1) has been identified as a putative cancer stem cell (CSC) marker in breast cancer. However, the clinicopathological and prognostic significance of this protein in breast cancer patients remains controversial. This meta-analysis was conducted to address the above issues using 15 publications covering 921 ALDH1A1+ cases and 2353 controls. The overall and subcategory analyses were performed to detect the association between ALDH1A1 expression and clinicopathological/prognostic parameters in breast cancer patients. The overall analysis showed that higher expression of ALDH1A1 is associated with larger tumor size, higher histological grade, greater possibility of lymph node metastasis (LNM), higher level expression of epidermal growth factor receptor 2 (HER2), and lower level expression of estrogen receptor (ER)/progesterone receptor (PR). The prognosis of breast cancer patients with ALDH1A1+ tumors was poorer than that of the ALDH1A1- patients. Although the relationships between ALDH1A1 expression and some clinicopathological parameters (tumor size, LNM, and the expression of HER2) was not definitive to some degree when we performed a subcategory analysis, the predictive values of ALDH1A1 expression for histological grade and survival of breast cancer patients were significant regardless of the different cutoff values of ALDH1A1 expression, the different districts where the patients were located, the different clinical stages of the patients, the difference in antibodies used in the studies, and the surgery status. Our results indicate that ALDH1A1 is a biomarker to predict tumor progression and poor survival of breast cancer patients. This marker should be taken into consideration in the development of new diagnostic and therapeutic program for breast cancer.

A microRNA Signature Associated with Early Recurrence in Breast Cancer

Abstract: Recurrent breast cancer occurring after the initial treatment is associated with poor outcome. A bimodal relapse pattern after surgery for primary tumor has been described with peaks of early and late recurrence occurring at about 2 and 5 years, respectively. Although several clinical and pathological features have been used to discriminate between low- and high-risk patients, the identification of molecular biomarkers with prognostic value remains an unmet need in the current management of breast cancer. Using microarray-based technology, we have performed a microRNA expression analysis in 71 primary breast tumors from patients that either remained disease-free at 5 years post-surgery (group A) or developed early (group B) or late (group C) recurrence. Unsupervised hierarchical clustering of microRNA expression data segregated tumors in two groups, mainly corresponding to patients with early recurrence and those with no recurrence. Microarray data analysis and RT-qPCR validation led to the identification of a set of 5 microRNAs (the 5-miRNA signature) differentially expressed between these two groups: miR-149, miR-10a, miR-20b, miR-30a-3p and miR-342-5p. All five microRNAs were down-regulated in tumors from patients with early recurrence. We show here that the 5-miRNA signature defines a high-risk group of patients with shorter relapse-free survival and has predictive value to discriminate non-relapsing versus early-relapsing patients (AUC = 0.993, p-value<0.05). Network analysis based on miRNA-target interactions curated by public databases suggests that down-regulation of the 5-miRNA signature in the subset of early-relapsing tumors would result in an overall increased proliferative and angiogenic capacity. In summary, we have identified a set of recurrence-related microRNAs with potential prognostic value to identify patients who will likely develop metastasis early after primary breast surgery.

Loss of histone H4K20 trimethylation predicts poor prognosis in breast cancer and is associated with invasive activity.

Abstract: Loss of histone H4 lysine 20 trimethylation (H4K20me3) is associated with multiple cancers, but its role in breast tumors is unclear. In addition, the pathological effects of global reduction in H4K20me3 remain mostly unknown. Therefore, a major goal of this study was to elucidate the global H4K20me3 level in breast cancer tissue and investigate its pathological functions. Levels of H4K20me3 and an associated histone modification, H3 lysine 9 trimethylation (H3K9me3), were evaluated by immunohistochemistry in a series of breast cancer tissues. Univariate and multivariate clinicopathological and survival analyses were performed. We also examined the effect of overexpression or knockdown of the histone H4K20 methyltransferases, SUV420H1 and SUV420H2, on cancer-cell invasion activity in vitro. H4K20me3, but not H3K9me3, was clearly reduced in breast cancer tissue. A reduced level of H4K20me3 was correlated with several aspects of clinicopathological status, including luminal subtypes, but not with HER2 expression. Multivariate analysis showed that reduced levels of H4K20me3 independently associated with lower disease-free survival. Moreover, ectopic expression of SUV420H1 and SUV420H2 in breast cancer cells suppressed cell invasiveness, whereas knockdown of SUV420H2 activated normal mammary epithelial-cell invasion in vitro. H4K20me3 was reduced in cancerous regions of breast-tumor tissue, as in other types of tumor. Reduced H4K20me3 level can be used as an independent marker of poor prognosis in breast cancer patients. Most importantly, this study suggests that a reduced level of H4K20me3 increases the invasiveness of breast cancer cells in a HER2-independent manner.

Oncoplastic breast conservation surgery: the new paradigm.

Abstract: Oncoplastic surgery combines plastic surgical techniques with sound surgical oncologic principles. The goal is to completely excise the cancer, with wide surgical margins while maintaining or improving cosmesis. For large, poorly defined, or unfavorably situated tumors, standard lumpectomies may lead to unacceptable cosmetic results in addition to close or involved resection margins. Similar problems may occur for smaller tumors in small breasts. Integration of the two surgical disciplines avoids or minimizes poor cosmetic results after wide excision. It increases the number of women who can be treated with breast-conserving surgery by allowing larger breast excisions with more acceptable cosmetic results. Oncoplastic surgery requires a multidisciplinary approach and thorough preoperative planning. It is absolutely necessary to enlist the cooperation and coordination of surgical oncology, plastic surgery, radiology, pathology, medical oncology, and radiation oncology. Oncoplastic surgery requires a philosophy that the appearance of the breast after tumor excision is important.

Intraoperative imaging of nipple perfusion patterns and ischemic complications in nipple-sparing mastectomies.

Abstract: Background Nipple-sparing mastectomies (NSM) have gained acceptance in the field of breast oncology. Ischemic complications involving the nipple–areolar complex (NAC) occur in 3–37 % of cases. Skin perfusion can be monitored intraoperatively using indocyanine green (IC-GREEN™, ICG) and a specialized infrared camera–computer system (SPY Elite™). The blood flow pattern to the breast skin and the NAC were evaluated and a classification scheme was developed.

Surgical Treatment of Borderline and Malignant Phyllodes Tumors: The Effect of the Extent of Resection and Tumor Characteristics on Patient Outcome

Abstract: Malignant phyllodes tumors are rare fibroepithelial breast neoplasms. Appropriate surgical management remains a subject of debate. The purpose of our study was to define optimal surgical treatment and to identify factors associated with outcome. After confirmatory pathology review, we identified 67 patients with borderline (n = 15) and malignant (n = 52) phyllodes tumors treated at our institution between 1971 and 2008. We used Cox proportional hazards models to evaluate associations between treatment, patient and tumor characteristics, and disease-free (DFS) and cancer-specific survival (CSS). Median patient age was 47 years. For 32 patients, definitive surgical treatment was wide local excision (WLE): 27 with margins ≥1 cm and 5 with margins 5 cm, mitotic rate ≥10/10 HPF, stromal overgrowth and cellularity (all p < 0.05) predicted DFS, whereas CSS was associated with the latter three variables. CSS was diminished for mastectomy patients who were significantly more likely to harbor tumors with adverse features. With long-term follow-up, extent of surgical resection did not affect DFS for patients with borderline and malignant phyllodes tumors. Tumor features, most notably stromal overgrowth, were predictive of recurrence and survival, suggesting these high-risk patients may benefit from additional therapeutic strategies.

More than 10-year follow-up after total en bloc spondylectomy for spinal tumors.

Abstract: There are many reports of en bloc resection for spinal tumors. However, no studies have evaluated the clinical outcomes with follow-up exceeding 10 years after surgery. We reviewed 82 patients who had undergone total en bloc spondylectomy (TES) before January 2002 and identified 29 (19 with primary tumors and 10 with metastatic tumors) who had survived for more than 10 years after surgery. We evaluated the clinical outcomes including patient-based outcomes using questionnaire. The questionnaire included subjective assessment of the results of TES and SF-36. Overall, 33 % of patients with metastases from kidney cancer and 25 % of those with metastases from thyroid cancer survived for more than 10 years after TES for solitary spinal metastases. Four patients with metastatic tumors had no evidence of disease at the time of survey. There were no tumor recurrences in any of the 23 patients who underwent TES as the primary surgery. No revision surgeries have been required as a result of instrumentation failure in any of the 29 patients. About 90 % of the patients were satisfied or very satisfied with the results of TES. The SF-36 results demonstrated that the both physical and mental health of patients with primary tumors was equivalent to those of healthy individuals, and the mental health of patients with metastatic tumors was almost similar to them. This study showed the long-term clinical outcomes after TES to be favorable. TES played an important role in the treatment strategy for spinal tumors including metastases.

Gross cystic disease fluid protein 15 (GCDFP-15) expression in breast cancer subtypes.

Abstract: Gross cystic disease fluid protein 15 (GCDFP-15), which is regulated by the androgen receptor (AR), is a diagnostic marker for mammary differentiation in histopathology. We determined the expression of GCDFP-15 in breast cancer subtypes, its potential prognostic and predictive value, as well as its relationship to AR expression. 602 pre-therapeutic breast cancer core biopsies from the phase III randomized neoadjuvant GeparTrio trial (NCT00544765) were investigated for GCDFP-15 expression by immunohistochemistry. Expression data were correlated with disease-free (DFS) and overall survival (OS) time as well as pathological complete response (pCR) to neoadjuvant chemotherapy. 239 tumors (39.7%) were GCDFP-15 positive. GCDFP-15 expression was positively linked to hormone receptor (HR) and HER2 positive tumor type, while most triple negative carcinomas were negative (p < 0.0001). GCDFP-15 was also strongly correlated to AR expression (p 0.001), and to the so-called molecular apocrine subtype (HR-/AR+, p < 0.0001). Higher rates of GCDFP-15 positivity were seen in tumors of lower grade (<0.0001) and negative nodal status (p = 0.008). GCDFP-15 positive tumors tended to have a more favourable prognosis than GCDFP-15 negative tumors (DFS (p = 0.052) and OS (p = 0.044)), which was not independent from other factors in multivariate analysis. GCDFP-15 expression was not linked to pCR. Histological apocrine differentiation was frequent in molecular apocrine carcinomas (60.7%), and was associated with GCDFP-15 within this group (p = 0.039). GCDFP-15 expression is higher in tumors with favorable prognostic features. GCDFP-15 expression is further a frequent feature of AR positive tumors and the molecular apocrine subtype. It might have reduced sensitivity as a diagnostic marker for mammary differentiation in triple negative tumors as compared to HR or HER2 positive tumor types.

Clinicopathological features and treatment outcomes of metastatic tumors in the stomach

Abstract: The metastasis of tumors to the stomach is rare, which underlies the clinical problems regarding their diagnosis and treatment. The present review summarizes the current knowledge regarding the clinicopathological characteristics, therapeutic strategies and outcomes for metastatic tumors in the stomach. The primary malignancies of the metastatic tumors in the stomach were most often breast cancers (27.9 %), followed by lung cancer (23.8 %), esophageal cancer (19.1 %), renal cell carcinoma (RCC; 7.6 %) and malignant melanoma (7.0 %). In cases of breast cancer and RCC as the primary malignancy, the median interval between the treatment of the primary tumor and diagnosis of the metastatic tumor in the stomach (IPM) was 50–78 and 75.6 months, respectively, highlighting the fact that the metastatic spread to the stomach may occur many years after the initial treatment of the cancer. In nine patients with metastatic gastric tumors arising from ovarian cancer, an endoscopic examination revealed submucosal tumors in six patients (66.7 %), with a median IPM of 30 months. Appropriate systemic treatment for these tumors is the preferred therapeutic strategy. Although solitary metachronous gastric metastasis several years after treatment of the primary tumor is an exceptionally rare event, surgical resection of metastatic gastric tumors may be recommended to control hemorrhaging or for selected tumors.

AQP5 Expression Predicts Survival in Patients with Early Breast Cancer

Abstract: Background Our previous study showed the association of aquaporin 5 (AQP5) up-regulation with cancer proliferation and migration in estrogen receptor (ER)-positive breast cancer cell line (MCF-7) and with unfavorable prognosis in a small number of patients with breast cancer. Accordingly, we analyzed the prognostic impact of AQP5 expression in a large number of patients with early breast cancer (EBC).

High serum levels of Dickkopf-1 are associated with a poor prognosis in prostate cancer patients

Abstract: The Wnt inhibitor Dickkopf-1 (DKK-1) has been linked to the progression of malignant bone disease by impairing osteoblast activity. In addition, there is increasing data to suggest direct tumor promoting effects of DKK-1. The prognostic role of DKK-1 expression in prostate cancer remains unclear. A prostate cancer tissue microarray (n = 400) was stained for DKK-1 and DKK-1 serum levels were measured in 80 patients with prostate cancer. The independent prognostic value of DKK-1 expression was assessed using multivariate analyses. DKK-1 tissue expression was significantly increased in prostate cancer compared to benign disease, but was not correlated with survival. However, high DKK-1 serum levels at the time of the diagnosis were associated with a significantly shorter overall and disease-specific survival. Multivariate analyses defined high serum levels of DKK-1 as an independent prognostic marker in prostate cancer (HR 3.73; 95%CI 1.44-9.66, p = 0.007). High DKK-1 serum levels are associated with a poor survival in patients with prostate cancer. In light of current clinical trials evaluating the efficacy of anti-DKK-1 antibody therapies in multiple myeloma and solid malignancies, the measurement of DKK-1 in prostate cancer may gain clinical relevance.

A Contemporary Large Single-Institution Evaluation of Resected Retroperitoneal Sarcoma

Abstract: Purpose Retroperitoneal sarcomas (RPS) are rare malignancies, comprising just 10–15 % of all soft-tissue sarcomas. These are challenging tumors to treat, with surgical resection being the only modality capable of providing a cure. This study analyzed the management and survival of patients resected at a large academic institution.