Cancer-Associated Fibroblasts Together with a Decline in CD8+ T Cells Predict a Worse Prognosis for Breast Cancer Patients.

BACKGROUND: Cancer-associated fibroblasts (CAFs) play a crucial role in tumor microenvironment regulation and cancer progression. This study assessed the significance and predictive potential of CAFs in breast cancer prognosis. METHODS: The study included 1503 breast cancer patients. Cancer-associated fibroblasts were identified using morphologic features from hematoxylin and eosin slides. The study analyzed clinicopathologic parameters, survival rates, immune cells, gene sets, and prognostic models using gene-set enrichment analysis, in silico cytometry, pathway analysis, in vitro drug-screening, and gradient-boosting machine (GBM)-learning. RESULTS: The presence of CAFs correlated significantly with young age, lymphatic invasion, and perineural invasion. In silico cytometry showed altered leukocyte subsets in the presence of CAFs, with decreased CD8+ T cells. Gene-set enrichment analysis showed associations with critical processes such as the epithelial-mesenchymal transition and immune modulation. Drug sensitivity analysis in breast cancer cell lines with varying fibroblast activation protein-α expression suggested that CAF-targeted therapies might enhance the efficacy of certain anticancer drugs including ARRY-520, ispinesib-mesylate, paclitaxel, and docetaxel. Integrating CAF presence with machine-learning improved survival prediction. For breast cancer patients, CAFs were independent prognostic markers for worse disease-specific survival and disease-free survival. CONCLUSION: This study highlighted the significance of CAFs in breast cancer biology and provided compelling evidence of their impact on patient outcomes and treatment response. The findings offer valuable insights into the potential of CAFs as prognostic and predictive biomarkers and support the development of CAF-targeted therapies to improve breast cancer management.

JAK2 Loss Arising From Tumor-Spread-Through-Air-Spaces (STAS) Promotes Tumor Progression by Suppressing CD8+ T Cells in Lung Adenocarcinoma: A Machine Learning Approach.

BACKGROUND: Tumor spread through air spaces (STAS) is a recently discovered risk factor for lung adenocarcinoma (LUAD). The aim of this study was to investigate specific genetic alterations and anticancer immune responses related to STAS. By using a machine learning algorithm and drug screening in lung cancer cell lines, we analyzed the effect of Janus kinase 2 (JAK2) on the survival of patients with LUAD and possible drug candidates. METHODS: This study included 566 patients with LUAD corresponding to clinicopathological and genetic data. For analyses of LUAD, we applied gene set enrichment analysis (GSEA), in silico cytometry, pathway network analysis, in vitro drug screening, and gradient boosting machine (GBM) analysis. RESULTS: The patients with STAS had a shorter survival time than those without STAS (P < 0.001). We detected gene set-related downregulation of JAK2 associated with STAS using GSEA. Low JAK2 expression was related to poor prognosis and a low CD8+ T-cell fraction. In GBM, JAK2 showed improved survival prediction performance when it was added to other parameters (T stage, N stage, lymphovascular invasion, pleural invasion, tumor size). In drug screening, mirin, CCT007093, dihydroretenone, and ABT737 suppressed the growth of lung cancer cell lines with low JAK2 expression. CONCLUSION: In LUAD, low JAK2 expression linked to the presence of STAS might serve as an unfavorable prognostic factor. A relationship between JAK2 and CD8+ T cells suggests that STAS is indirectly related to the anticancer immune response. These results may contribute to the design of future experimental research and drug development programs for LUAD with STAS.

Impact of the ACOSOG Z0011 trial on surgical practice in Asian patients: trends in axillary surgery for breast cancer from a Korean Breast Cancer Registry analysis.

BACKGROUND: Since the publication of the Z0011 trial, practice-changing clinical guidelines for breast surgery have been developed. Although recent studies confirmed the feasibility of the Z0011 strategy in Asian populations, there has been no study on the trends of axillary surgery in Asian cohort. This study aimed to investigate the time trend of axillary surgery for breast cancer from a Korean Breast Cancer Registry to understand the impact of the Z0011 trial in Asian patients. METHODS: We collected prospectively constructed data from the nationwide Korean Breast Cancer Registry (KBCR). We identified patients who underwent sentinel node biopsy followed by breast-conserving surgery from 2011 to 2018 and were found to have pathological stage T1-2N1-3M0 disease. Regression analyses were performed to compare the downward trend of axillary lymph node dissection (ALND) in Korean cohort with that previously reported in a Dutch cohort. RESULTS: From KBCR data, 7478 patients met the inclusion criteria. The proportion of ALND significantly decreased from 2011 (76.6%) to 2018 (47.5%). Multivariate analysis revealed that earlier years at diagnosis, larger tumor size, and lymphatic invasion were associated with a higher odds ratio of performing ALND. Compared to the Dutch cohort, the downward trend of ALND in Korea was significantly more gradual (annual percent change: 37.2 vs. 5.8%, p < 0.001). CONCLUSIONS: This study demonstrated a downward trend of ALND in Korean patients with breast cancer. However, the rate of decrease was significantly slower than that in the Dutch cohort.

Outcomes of laparoscopic primary gastrectomy with curative intent for gastric perforation: experience from a single surgeon.

BACKGROUND: Gastric cancer perforation is rare and difficult to distinguish from gastric ulcer perforation before surgery. Peritonitis caused by gastric perforation requires emergency surgery. The optimal surgical strategy for gastric perforation has not been established. MATERIAL AND METHODS: Data from 43 patients who underwent primary gastrectomy with curative intent for gastric perforation between June 2010 and November 2019 were reviewed. Patients were classified into gastric ulcer and gastric cancer groups. Early surgical outcomes and overall survival were assessed. RESULTS: There were no significant differences in clinical characteristics between the two groups except regarding preoperative shock. Laparoscopic gastrectomy was performed in 35 of 43 patients. There were no conversions to open surgery. The surgical findings demonstrated that the gastric cancer group had larger mass lesions with significantly larger perforations than did the gastric ulcer group. There were no significant differences in early surgical outcomes. Severe postoperative complications occurred in nine patients, five of whom died within one month of surgery. The majority of patients (90%) had stage III or IV gastric cancer. The 5-year survival rate was 19.5%. CONCLUSION: We found no definitive differences in clinical characteristics distinguishing gastric cancer from ulcers. Considering our surgical outcomes, laparoscopic primary gastrectomy performed by an expert is a useful technique for emergency gastric perforation. However, unless an expert is available, caution should be used when selecting laparoscopic primary gastrectomy with curative intent as a surgical method.

The application of bacteriophage to control Cronobacter sakazakii planktonic and biofilm growth in infant formula milk.

The goal was to identify the biofilm-forming ability of Cronobacter sakazakii on surfaces of stainless steel (SS) and silicone rubber (SR) in contact with infant formula milk. Two representative bacteriophages (PBES04 and PBES19) were used to control the growth of C. sakazakii as well as its biofilm forming ability on either SS or SR surfaces. Bacterial growth was confirmed at 20 °C when PBES04 and PBES19 were used, whereas C. sakazakii was not normally detected in infant formula milk treated with both bacteriophages for 6 h. In an additional biofilm reduction experiment, the biofilm on SS or SR surfaces were reduced by 3.07 and 1.92 log CFU cm-2, respectively after PBES04 treatment, and 3.06 and 2.14 log CFU cm-2, respectively, after PBES19 treatment. These results demonstrate that bacteriophages can be effective in inactivating C. sakazakii in biofilms which could potentially increase food safety in commercial facilities.

The prognostic value of HER2 status and efficacy of anti-HER2 therapy in patients with HR-positive mucinous breast cancer: a nationwide study from the Korean Breast Cancer Society.

PURPOSE: The effect of human epidermal growth factor receptor 2 (HER2) status on mucinous carcinoma (MC) of the breast is unknown due to the rarity of HER2-positive cases. We evaluated the prognostic value of HER2 status and the efficacy of anti-HER2 therapy in patients with hormone receptor (HR)-positive MC. METHODS: From the data of 154,661 patients recorded in the Korean Breast Cancer Registry between January 1990 and August 2016, 3076 (2.0%) were diagnosed with MC. Overall survival (OS) according to HER2 status and anti-HER2 therapy was analyzed using Kaplan-Meier estimates. Multivariate analysis was performed using the Cox proportional hazards model to estimate the adjusted hazards ratio (HR) for clinicopathologic factors. RESULTS: A total of 2716 HR-positive MC patients were enrolled and followed up for a median 100.1 months. Of these, 2094 (77.1%) were HER2-negative and 228 (8.4%) were HER2-positive. HR-positive, HER2-positive MC patients had more advanced pathologic tumor stages (T3 or T4) (p = 0.001), more axillary lymph node involvement (p < 0.001), higher nuclear grade (p < 0.001), and more lymphovascular invasion (p = 0.012) than HER2-negative patients. Subgroup analysis of HR-positive, node-positive MC showed that HER2-positive MC was an independent prognostic factor for OS (HR = 2.657; 95% CI, 1.665-4.241; p < 0.001). HR-positive, node-positive, and HER2-negative MC had significantly longer OS than HER2-positive MBC (p = 0.017). The node-positive subgroup that received anti-HER2 therapy had increased OS, although not significantly (p = 0.224). CONCLUSION: Our nationwide database study revealed that HER2-positive status was associated with worse prognosis in HR-positive and node-positive MC. Anti-HER2 therapy might be beneficial in HR-positive, node-positive, and HER2-positive MC.

Ectopic expression of the Stabilin2 gene triggered by an intracisternal A particle (IAP) element in DBA/2J strain of mice.

Stabilin2 (Stab2) encodes a large transmembrane protein which is predominantly expressed in the liver sinusoidal endothelial cells (LSECs) and functions as a scavenger receptor for various macromolecules including hyaluronans (HA). In DBA/2J mice, plasma HA concentration is ten times higher than in 129S6 or C57BL/6J mice, and this phenotype is genetically linked to the Stab2 locus. Stab2 mRNA in the LSECs was significantly lower in DBA/2J than in 129S6, leading to reduced STAB2 proteins in the DBA/2J LSECs. We found a retrovirus-derived transposable element, intracisternal A particle (IAP), in the promoter region of Stab2DBA which likely interferes with normal expression in the LSECs. In contrast, in other tissues of DBA/2J mice, the IAP drives high ectopic Stab2DBA transcription starting within the 5' long terminal repeat of IAP in a reverse orientation and continuing through the downstream Stab2DBA. Ectopic transcription requires the Stab2-IAP element but is dominantly suppressed by the presence of loci on 59.7-73.0 Mb of chromosome (Chr) 13 from C57BL/6J, while the same region in 129S6 requires additional loci for complete suppression. Chr13:59.9-73 Mb contains a large number of genes encoding Krüppel-associated box-domain zinc-finger proteins that target transposable elements-derived sequences and repress their expression. Despite the high amount of ectopic Stab2DBA transcript in tissues other than liver, STAB2 protein was undetectable and unlikely to contribute to the plasma HA levels of DBA/2J mice. Nevertheless, the IAP insertion and its effects on the transcription of the downstream Stab2DBA exemplify that stochastic evolutional events could significantly influence susceptibility to complex but common diseases.

Prognostic Implication of Body Mass Index on Survival Outcomes in Surgically Treated Nonmetastatic Renal Cell Carcinoma: A Single-Institutional Retrospective Analysis of a Large Cohort.

PURPOSE: Obesity is a well-known risk factor for renal cell carcinoma (RCC). However, the prognostic role of obesity in RCC has not been clearly established thus far. We aim to assess the effect of preoperative body mass index (BMI) on survival outcomes in nonmetastatic RCC patients. PATIENTS AND METHODS: We retrospectively analyzed data on 2329 patients who underwent curative surgery for RCC between 2000 and 2014 in a single institution. Patients were divided into normal (< 23 kg/m2), overweight (23-24.9 kg/m2), and obese (≥ 25 kg/m2) groups depending on cutoffs for Asian population. Kaplan-Meier analysis with log-rank test was used to estimate and compare survival outcomes, including recurrence-free, overall, and cancer-specific survival, among each BMI group. The influence of BMI on each survival outcome was evaluated using multivariate Cox regression analyses. RESULTS: Obese patients presented favorable 5-year recurrent-free (90.7% vs 84.9%, p < 0.001), overall (91.8% vs 86.8%, p = 0.002), and cancer-specific (94.8% vs 89.4%, p = 0.002) survival rates than the normal group. Multivariate analyses revealed that increasing BMI was an independent predictor of favorable survival outcomes (all p values < 0.05). In particular, overweight (p = 0.009) and obese (p = 0.009) patients showed better cancer-specific survival compared with normal patients. CONCLUSIONS: Our data suggest that overweight and obesity defined based on BMI are generally related to favorable survival outcomes after surgery for RCC. Additional basic research is required to find out the biological mechanisms explaining the correlation between BMI and survival outcomes.

Naphthalene Benzimidazole Based Neutral Ir(III) Emitters for Deep Red Organic Light-Emitting Diodes.

Rigid naphthalene benzimidazole (NBI) based ligands (L1 and L2) are synthesized and utilized to make deep red phosphorescent cyclometalated iridium(III) complexes ([Ir(NBI)2(PyPzCF3)] (1) and [Ir(DPANBI)2(PyPzCF3)] (2)). Complexes 1 and 2 are prepared from the reaction of L1/L2 with the aid of ancillary ligands (PyPzCF3, 2-(3-(trifluoromethyl)-1H-pyrazol-5-yl)pyridine) in a two step method. The complexes are characterized by analytical and spectroscopic methods, as well as X-ray diffraction for 1. These complexes show a strong emission in the range of 635-700 nm that extends up to the near-infrared region (800 nm). The introduction of the diphenylamino (DPA) donor group on the naphthalene unit leads to a further red-shift in the emission. The complexes exhibit radiative quantum efficiency (ΦPL) of 0.27-0.29 in poly(methylmethacrylate) film and relatively short phosphorescence decay lifetimes (τ = 1.1-3.5 µs). The structural, electronic, and optical properties are investigated with the support of density functional theory (DFT) and time-dependent-DFT calculations. The calculation results indicate that the lowest-lying triplet (T1) excited state of 1 has a mixed metal-to-ligand charge transfer (3MLCT) and ligand-centered (3LC) character, while 2 shows a dominant 3LC character. Deep red-emitting organic light-emitting diodes fabricated using 1 as a dopant display a maximum external quantum efficiency of 10.9% with the CIE color coordinates of (0.690, 0.294), with an emission centered at 644 and 700 nm. Similarly, the emitter 2 also shows a maximum external quantum efficiency of 6.9% with emissions at 657 and 722 nm.

Novel nomograms to predict recurrence and progression in primary non-muscle-invasive bladder cancer: validation of predictive efficacy in comparison with European Organization of Research and Treatment of Cancer scoring system.

PURPOSE: To develop and validate novel nomograms to predict recurrence and progression after transurethral resection of bladder tumor (TURBT) in Korean patients with non-muscle-invasive bladder cancer (NMIBC). METHODS: We retrospectively analyzed the clinical data on 970 newly diagnosed NMIBC patients after TURBT between 2000 and 2013 in a single institution. We used multivariate Cox proportional hazard models to identify the significant predictors of recurrence and progression, which resulted in the construction of the nomograms predicting the 5-year probability of recurrence and progression. We internally validated the nomograms using the area under the receiver-operating characteristics' curves and calibration plots. In addition, the clinical usefulness of each nomogram was assessed and compared with that of the European Organization of Research and Treatment of Cancer (EORTC)-scoring system using decision curve analysis (DCA). RESULTS: The significant factors related to recurrence were gross hematuria at diagnosis, previous or concomitant upper urinary tract urothelial carcinoma (UTUC), pT1 tumor, high tumor grade, multiple tumors, and intravesical therapy. The significant predictors of progression were previous or concomitant UTUC, pT1 tumor, high tumor grade, carcinoma in situ, and lymphovascular invasion. The 5-year predictive accuracy of each nomogram was 65% for recurrence and 70% for progression, respectively. Compared with the EORTC-scoring system, the nomograms were generally well calibrated. On DCA, each nomogram presented better net benefit gains than did the EORTC-scoring system across a wide range of threshold probabilities. CONCLUSIONS: Our novel nomograms are not completely accurate, but they show a reasonable level of discriminative ability, adequate calibration, and meaningful net benefit gain for the prediction of recurrence and progression after TURBT in Korean NMIBC patients. Additional external validation will be required to generalize the nomograms which we developed.

Prolactin alters blood pressure by modulating the activity of endothelial nitric oxide synthase.

Increased levels of a cleaved form of prolactin (molecular weight 16 kDa) have been associated with preeclampsia. To study the effects of prolactin on blood pressure (BP), we generated male mice with a single-copy transgene (Tg; inserted into the hypoxanthine-guanine phosphoribosyltransferase locus) that enables inducible hepatic production of prolactin and its cleavage product. The Tg is driven by the indole-3-carbinol (I3C)-inducible rat cytochrome P450 1A1 promoter. When the Tg mice were fed normal chow (NC), plasma prolactin concentrations were comparable to those in female WT mice in the last third of pregnancy, and BP was lower than in WT mice (∼95 mm Hg vs. ∼105 mm Hg). When the Tg mice were fed chow containing IC3, plasma prolactin concentrations increased threefold, BP increased to ∼130 mm Hg, and cardiac function became markedly impaired. IC3 chow did not affect the WT mice. Urinary excretion of nitrite/nitrate and the amount of Ser1177-phosphorylated endothelial nitric oxide (NO) synthase (eNOS) were significantly greater in the Tg mice fed NC than in WT mice, as they are during pregnancy. However, when I3C was fed, these indicators of NO production became significantly less in the Tg mice than in WT mice. The effects of increased plasma prolactin were abolished by a genetic absence of eNOS. Thus, a threefold increase in plasma prolactin is sufficient to increase BP significantly and to markedly impair cardiac function, with effects mediated by NO produced by eNOS. We suggest that pregnant women with abnormally high prolactin levels may need special attention.

High Elmo1 expression aggravates and low Elmo1 expression prevents diabetic nephropathy.

Human genome-wide association studies have demonstrated that polymorphisms in the engulfment and cell motility protein 1 gene (ELMO1) are strongly associated with susceptibility to diabetic nephropathy. However, proof of causation is lacking. To test whether modest changes in its expression alter the severity of the renal phenotype in diabetic mice, we have generated mice that are type 1 diabetic because they have the Ins2(Akita) gene, and also have genetically graded expression of Elmo1 in all tissues ranging in five steps from ∼30% to ∼200% normal. We here show that the Elmo1 hypermorphs have albuminuria, glomerulosclerosis, and changes in the ultrastructure of the glomerular basement membrane that increase in severity in parallel with the expression of Elmo 1. Progressive changes in renal mRNA expression of transforming growth factor ß1 (TGFß1), endothelin-1, and NAD(P)H oxidase 4 also occur in parallel with Elmo1, as do the plasma levels of cystatin C, lipid peroxides, and TGFß1, and erythrocyte levels of reduced glutathione. In contrast, Akita type 1 diabetic mice with below-normal Elmo1 expression have reduced expression of these various factors and less severe diabetic complications. Remarkably, the reduced Elmo1 expression in the 30% hypomorphs almost abolishes the pathological features of diabetic nephropathy, although it does not affect the hyperglycemia caused by the Akita mutation. Thus, ELMO1 plays an important role in the development of type 1 diabetic nephropathy, and its inhibition could be a promising option for slowing or preventing progression of the condition to end-stage renal disease.

Impact of serum 25-OH vitamin D level on lower urinary tract symptoms in men: a step towards reducing overactive bladder.

OBJECTIVES: To evaluate the impact of serum vitamin D level on male lower urinary tract symptoms (LUTS). PATIENTS AND METHODS: Men with LUTS who visited the outpatient clinic of the urology department at one of two hospitals between March 2014 and April 2017 were eligible for inclusion in the study. The impact of vitamin D on LUTS was evaluated using multivariate analysis to adjust for age, body mass index, prostate-specific antigen, testosterone, glycated haemoglobin, physical activity and prostate volume. To exclude the effect of seasons, we also analysed the impact during each season. RESULTS: Vitamin D level was lowest in winter. According to the International Prostate Symptom Score (IPSS) and Overactive Bladder Symptom Score (OABSS), the severity of LUTS peaked in winter. There were no seasonal differences between prostate volume, maximum urinary flow rate (Qmax ) and post-void residual urine volume (PVR). For all patients, multivariate analysis showed that lower vitamin D level was significantly associated with higher total OABSS, whereas it was not associated with prostate volume, Qmax , PVR or total IPSS. In winter, lower vitamin D level was significantly associated with higher total OABSS based on multivariate analysis, whereas it was not during other seasons. In patients with vitamin D deficiency, the total OABSS significantly decreased after vitamin D replacement. The greatest improvement in total OABSS was associated with lower pre-treatment total OABSS and higher post-treatment vitamin D level. CONCLUSIONS: Vitamin D deficiency in men with LUTS may play a role in aggravated overactive bladder (OAB) symptoms, especially in winter. Increasing vitamin D level in patients with vitamin D deficiency appears to alleviate OAB symptoms.

Low TGFß1 expression prevents and high expression exacerbates diabetic nephropathy in mice.

Nephropathy develops in many but not all patients with long-standing type 1 diabetes. Substantial efforts to identify genotypic differences explaining this differential susceptibility have been made, with limited success. Here, we show that the expression of the transforming growth factor ß1 gene (Tgfb1) affects the development of diabetic nephropathy in mice. To do this we genetically varied Tgfb1 expression in five steps, 10%, 60%, 100%, 150%, and 300% of normal, in mice with type 1 diabetes caused by the Akita mutation in the insulin gene (Ins2(Akita)). Although plasma glucose levels were not affected by Tgfb1 genotype, many features of diabetic nephropathy (mesangial expansion, elevated plasma creatinine and urea, decreased creatinine clearance and albuminuria) were progressively ameliorated as Tgfb1 expression decreased and were progressively exacerbated when expression was increased. The diabetic 10% hypomorphs had comparable creatinine clearance and albumin excretion to wild-type mice and no harmful changes in renal morphology. The diabetic 300% hypermorphs had ∼1/3 the creatinine clearance of wild-type mice, >20× their albumin excretion, ∼3× thicker glomerular basement membranes and severe podocyte effacement, matching human diabetic nephropathy. Switching Tgfb1 expression from low to high in the tubules of the hypomorphs increased their albumin excretion more than 10-fold but creatinine clearance remained high. Switching Tgfb1 expression from low to high in the podocytes markedly decreased creatinine clearance, but minimally increased albumin excretion. Decreasing expression of Tgfb1 could be a promising option for preventing loss of renal function in diabetes.

Endothelin-1 critically influences cardiac function via superoxide-MMP9 cascade.

We have generated low-expressing and high-expressing endothelin-1 genes (L and H) and have bred mice with four levels of expression: L/L, ∼20%; L/+, ∼65%; +/+ (wild type), 100%; and H/+, ∼350%. The hypomorphic L allele can be spatiotemporally switched to the hypermorphic H allele by Cre-loxP recombination. Young adult L/L and L/+ mice have dilated cardiomyopathy, hypertension, and increased plasma volumes, together with increased ventricular superoxide levels, increased matrix metalloproteinase 9 (Mmp9) expression, and reduced ventricular stiffness. H/+ mice have decreased plasma volumes and significantly heavy stiff hearts. Global or cardiomyocyte-specific switching expression from L to H normalized the abnormalities already present in young adult L/L mice. An epithelial sodium channel antagonist normalized plasma volume and blood pressure, but only partially corrected the cardiomyopathy. A superoxide dismutase mimetic made superoxide levels subnormal, reduced Mmp9 overexpression, and substantially improved cardiac function. Genetic absence of Mmp9 also improved cardiac function, but increased superoxide remained. We conclude that endothelin-1 is critical for maintaining normal contractile function, for controlling superoxide and Mmp9 levels, and for ensuring that the myocardium has sufficient collagen to prevent overstretching. Even a modest (∼35%) decrease in endothelin-1 gene (Edn1) expression is sufficient to cause cardiac dysfunction.

Identifying long-term survivors among metastatic breast cancer patients undergoing primary tumor surgery.

PURPOSE: The prognostic role of primary tumor surgery in women with metastatic breast cancer at diagnosis is contentious. A subset of patients who will benefit from aggressive local treatment is needed to be identified. Using a nationwide database, we developed and validated a predictive model to identify long-term survivors among patients who had undergone primary tumor surgery. METHODS: A total of 150,043 patients were enrolled in the Korean Breast Cancer Registry between January 1990 and December 2014. Of these, 2332 (1.6%) presented with distant metastasis at diagnosis. Using Cox proportional hazards regression, we developed and validated a model that predicts survival in patients who undergo primary tumor surgery, based on the clinicopathological features of the primary tumor. RESULTS: A total of 2232 metastatic breast cancer patients were reviewed. Of these, 1541 (69.0%) patients had undergone primary tumor surgery. The 3-year survival rate was 62.6% in this subgroup. Among these patients, advanced T-stage, high-grade tumor, lymphovascular invasion, negative estrogen receptor status, high Ki-67 expression, and abnormal CA 15-3 and alkaline phosphatase levels were associated with poor survival. A prediction model was developed based on these factors, which successfully identified patients with remarkable survival (score 0-3, 3-year survival rate 87.3%). The clinical significance of the model was also validated with an independent dataset. CONCLUSIONS: We have developed a predictive model to identify long-term survivors among women who undergo primary tumor surgery. This model will provide guidance to patients and physicians when considering surgery as a treatment modality for metastatic breast cancer.

Development of Urinary Bladder Pre-Neoplasia by Schistosoma haematobium Eggs and Chemical Carcinogen in Mice.

Schistosoma haematobium is a biocarcinogen of human urinary bladder (UB). The present study investigated developing UB cancer mouse model by injecting S. haematobium eggs into the bladder wall and introduction of chemical carcinogens. Histopathological findings showed mild hyperplasia to epithelial vacuolar change, and high grade dysplasia. Squamous metaplasia was observed in the S. haematobium eggs+NDMA group at week 12 but not in other groups. Immunohistochemistry revealed significantly high expression of Ki-67 in urothelial epithelial cells of the S. haematobium eggs+BBN group at week 20. The qRT-PCR showed high expression of p53 gene in S. haematobium eggs group at week 4 and S. haematobium eggs+BBN group at week 20. E-cadherin and vimentin showed contrasting expression in S. haematobium eggs+BBN group. Such inverse expression of E-cadherin and vimentin may indicate epithelial mesenchymal transition in the UB tissue. In conclusion, S. haematobium eggs and nitrosamines may transform UB cells into squamous metaplasia and dysplasia in correlation with increased expression of Ki-67. Marked decrease in E-cadherin and increase in p53 and vimentin expressions may support the transformation. The present study introduces a promising modified animal model for UB cancer study using S. haematobium eggs.

Sparganosis of the Unilateral Breast: A Case Report.

Sparganosis is a parasitic infection caused by the sparganum, the plercercoid of the genus Spirometra. The preoperative diagnosis of breast sparganosis is difficult in most cases because it is a rare parasitic infection less than 2% of all cases. We report a 62-year-old woman case of breast sparganosis that were confirmed by surgical removal of worms from the right breast. The radiologic images of the patient also revealed characteristic features of breast sparganosis. The patient described the migrating palpable breast mass, which strongly suggested the possibility of breast sparganosis. The treatment of choice and confirmative diagnosis for sparganosis are complete surgical extraction of the sparganum irrespective of infected site. Inspection of the mass site with detailed medical history and radiological examinations are important for preoperative diagnosis of sparganosis patients.

Laparoscopic radical nephroureterectomy is associated with worse survival outcomes than open radical nephroureterectomy in patients with locally advanced upper tract urothelial carcinoma.

PURPOSE: To compare survival outcomes between laparoscopic radical nephroureterectomy (LRNU) and open radical nephroureterectomy (ORNU) in upper urinary tract urothelial carcinoma (UTUC) patients. METHODS: We retrospectively analyzed the data of 371 UTUC patients who underwent ORNU (n = 271) or LRNU (n = 100) between 1992 and 2012. The survival outcomes included intravesical recurrence (IVR)-free survival, overall survival (OS), and cancer-specific survival (CSS). The Kaplan-Meier method and log-rank test were used to estimate and compare survival curves between groups. Factors associated with survival outcomes were evaluated using univariable and multivariable Cox proportional hazard models. RESULTS: The three-year IVR-free survival rates were similar between the ORNU and LRNU groups (59.9 and 61.7 %, p = 0.267). However, the LRNU group showed worse five-year OS (59.1 vs. 75.2 %, p = 0.027) and CSS (66.1 vs. 80.2 %, p = 0.015) rates than the ORNU group. In particular, on stratifying the study cohort by pathological stages, significant differences in OS (p = 0.007) and CSS (p = 0.005) between the surgical approaches were observed only in locally advanced disease (pT3/T4). In multivariable analysis, LRNU was an independent predictor of worse OS (p = 0.001) and CSS (p = 0.006) than ORNU. Likewise, in multivariable analysis in patients with pT3/T4 stage, LRNU was significantly associated with worse OS (hazard ratio [HR] 2.59, p = 0.001) and CSS (HR 2.50, p = 0.005). CONCLUSIONS: Our data suggest that in UTUC patients, LRNU, compared to ORNU, is generally associated with unfavorable OS and CSS results. In particular, LRNU should be performed in locally advanced UTUC patients after careful consideration of its impact on patient survival.