Incidence Trends of Gastroenteropancreatic Neuroendocrine Tumors in the United States.

BACKGROUND & AIMS: Although multiple studies have reported an increasing incidence of gastroenteropancreatic neuroendocrine tumors (GEP-NETs) over the past decades, there are limited national data on recent trends. Using a population-based registry, we evaluated GEP-NET incidence trends in the United States population from 1975 through 2012, based on age, calendar year at diagnosis, and year of birth. METHODS: GEP-NET cases from 1975 through 2012 were identified from the most recent version of the Surveillance, Epidemiology, and End Results registry using histologic and site codes. We calculated overall annual incidence, age-adjusted incidence (number of cases per 100,000), annual percent change (APC), and average APC by 5-year age intervals. We also evaluated the incidence rates by age, period, and birth year cohorts. RESULTS: We identified 22,744 patients with GEP-NETs. In adults 25-39 years old, GEP-NET incidence rates decreased from the mid-1970s to the early 1980s, then increased until 2012. In adults ages 40 years and older or young adults ages 15-24 years, incidence rates generally increased continuously from 1975 through 2012. Adults ages 40-69 years had the most rapid increases in average APC (approximately 4%-6% per year). Overall incidence rates were highest in adults 70-84 years old. Since the inception of the Surveillance, Epidemiology, and End Results registry, GEP-NET incidence has increased in consecutive birth cohorts. CONCLUSION: The incidence of GEP-NET continues to increase-particularly in older adults. More recent generations have had higher GEP-NET incidence rates than more distant generations.

Assessment of organotin and tin-free antifouling paints contamination in the Korean coastal area.

Twelve organotins (methyl-, octyl-, butyl-, and phenyl-tin), and eight tin-free antifouling paints and their degradation products were measured in marine sediments from the Korean coastal area, and Busan and Ulsan bays, the largest harbor area in Korea. The total concentration of tin-free antifouling paints was two- to threefold higher than the total concentration of organotins. Principal component analysis was used to identify sites with relatively high levels of contamination in the inner bay area of Busan and Ulsan bays, which were separated from the coastal area. In Busan and Ulsan bays, chlorothalonil and DMSA were more dominant than in the coastal area. However, Sea-Nine 211 and total diurons, including their degradation products, were generally dominant in the Korean coastal area. The concentrations of tin and tin-free compounds were significantly different between the east and west coasts.

Survival Improvement in Korean Breast Cancer Patients Due to Increases in Early-Stage Cancers and Hormone Receptor Positive/HER2 Negative Subtypes: A Nationwide Registry-Based Study.

PURPOSE: The aim of this study was to investigate whether the observed changes over time in the survival rates vary according to the intrinsic subtypes of breast cancer diagnosed. METHODS: Data from 46,320 breast cancer patients in the Korean Breast Cancer Registry who underwent surgery between 1999 and 2006 were reviewed. Among them, results from 25,887 patients with available data about the status of estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 (HER2) were analyzed. Patients were classified into two cohorts according to the year in which they underwent surgery: 1999-2002 and 2003-2006. RESULTS: The patients treated in the latter time period showed significantly better overall survival (OS) compared with those in the former period when adjusted for follow-up duration. The proportion of hormone receptor+/HER2-subtype and stage I breast cancer were significantly higher in the latter period (47.4% vs. 54.6%, p<0.001; 31.0% vs. 39.6%, p<0.001, respectively). Improvement in OS between the former and latter periods was seen in all subtypes of breast cancer, including triple-negative cancers (all p-values <0.001 in univariate and multivariate analyses). CONCLUSION: Improvement in survival in Korean breast cancer patients over the study years is being observed in all subtypes of breast cancer, implying that increases in both early-stage detection and the proportion of less aggressive cancers contribute to this improvement.

Filopodial morphology correlates to the capture efficiency of primary T-cells on nanohole arrays.

Nanostructured surfaces emerge as a new class of material for capture and separation of cell populations including primary immune cells and disseminating rare tumor cells, but the underlying mechanism remains elusive. Although it has been speculated that nanoscale topological structures on cell surface are involved in the cell capture process, there are no studies that systematically analyze the relation between cell surface structures and the capture efficiency. Here we report on the first mechanistic study by quantifying the morphological parameters of cell surface nanoprotrusions, including filopodia, lamellipodia, and microvilli in the early stage of cell capture (< 20 min) in correlation to the efficiency of separating primary T lymphocytes. This was conducted by using a set of nanohole arrays (NHAs) with varying hole and pitch sizes. Our results showed that the formation of filopodia (e.g., width of filopodia and the average number of the filopodial filaments per cell) depends on the feature size of the nanostructures and the cell separation efficiency is strongly correlated to the number of filopodial fibers, suggesting a possible role of early stage mechanosensing and cell spreading in determining the efficiency of cell capture. In contrast, the length of filopodial filaments was less significantly correlated to the cell capture efficiency and the nanostructure dimensions of the NHAs. This is the first mechanistic study on nanostructure-based immune cell capture and provides new insights to not only the biology of cell-nanomaterial interaction but also the design of new rare cell capture technologies with improved efficiency and specificity.

Nanowire array chips for molecular typing of rare trafficking leukocytes with application to neurodegenerative pathology.

Despite the presence of the blood-brain barrier (BBB) that restricts the entry of immune cells and mediators into the central nervous system (CNS), a small number of peripheral leukocytes can traverse the BBB and infiltrate into the CNS. The cerebrospinal fluid (CSF) is one of the major routes through which trafficking leukocytes migrate into the CNS. Therefore, the number of leukocytes and their phenotypic compositions in the CSF may represent important sources to investigate immune-to-brain interactions or diagnose and monitor neurodegenerative diseases. Due to the paucity of trafficking leucocytes in the CSF, a technology capable of efficient isolation, enumeration, and molecular typing of these cells in the clinical settings has not been achieved. In this study, we report on a biofunctionalized silicon nanowire array chip for highly efficient capture and multiplexed phenotyping of rare trafficking leukocytes in small quantities (50 microliters) of clinical CSF specimens collected from neurodegenerative disease patients. The antibody coated 3D nanostructured materials exhibited vastly improved rare cell capture efficiency due to high-affinity binding and enhanced cell-substrate interactions. Moreover, our platform creates multiple cell capture interfaces, each of which can selectively isolate specific leukocyte phenotypes. A comparison with the traditional immunophenotyping using flow cytometry demonstrated that our novel silicon nanowire-based rare cell analysis platform can perform rapid detection and simultaneous molecular characterization of heterogeneous immune cells. Multiplexed molecular typing of rare leukocytes in CSF samples collected from Alzheimer's disease patients revealed the elevation of white blood cell counts and significant alterations in the distribution of major leukocyte phenotypes. Our technology represents a practical tool for potentially diagnosing and monitoring the pathogenesis of neurodegenerative diseases by allowing an effective hematological analysis of the CSF from patients.

Effect of thiourea on electrochemical nucleation and electrochemical impedance spectroscopy of electrodeposited tin on a copper substrate in a sulfate bath.

The effect of thiourea on the electrochemical nucleation of tin on a copper substrate from a sulfate bath was studied using voltammetry, chronoamperometry, electrochemical impedance spectroscopy, and scanning electron microscopy. Without thiourea, electrodeposition of tin showed very poor surface coverage. However, re-nucleation and growth of tin occurred after the addition of thiourea. In particular, very rapid re-nucleation and growth behavior of tin were observed when up to 6 g/L of thiourea was added. Furthermore, impedance analysis allowed the estimation of the change in the growth behavior of tin when up to 6 g/L of thiourea was added.

Temperature-dependent thermal conductivities of 1D semiconducting nanowires via four-point-probe 3-ω method.

We report on a systematic study of the thermal transport characteristics of both as-grown zinc oxide and gallium nitride nanowires (NWs) via the four-point-probe 3-ω method in the temperature range 130-300 K. Both as-grown NWs were synthesized by a vapor-liquid-solid growth mechanism, and show clear n-type semiconducting behavior without any defects, which enables both the NWs to be promising candidates for thermoelectric materials. To measure the thermal conductivities of both NWs with lower heat loss and measurement errors, the suspended structures were formed by a combination of an e-beam lithography process and a random dispersion method. The measured thermal conductivities of both NWs are greatly reduced compared to their bulk materials due to the enhanced phonon scattering via the size effect and dopants (impurities). Furthermore, we observed that the Umklapp peaks of both NWs are shifted to a higher temperature than those of their bulk counterparts, indicating that phonon-boundary scattering dominates over other phonon scattering due to the size effect.

Association of Human Epidermal Growth Factor Receptor 2 with Radiotherapy Resistance in Patients with T1N0M0 Breast Cancer.

PURPOSE: Preclinical studies have shown that human epidermal growth factor receptor 2 (HER2) status is associated with resistance to radiotherapy (RT). In this study, we evaluated the overall survival of a T1N0M0 breast cancer cohort in Korea according to the use of RT and the HER2 status. METHODS: We analyzed data collected from 11,552 patients with invasive breast cancer who were enrolled in the Korean Breast Cancer Society Registration Program between 1999 and 2007. Data on the TNM stage, estrogen receptor status, progesterone receptor status, HER2 status, operation method, and the use of RT were analyzed. RESULTS: The median follow-up period was 51 months. A significant improvement in overall survival after RT was observed only in the HER2(-) group. In this group, the 10-year overall survival rate was 95.5% for patients who did not receive RT and 96.3% for patients who received RT (p=0.037). In contrast, in the HER2(+) group, RT was not associated with a survival benefit (p=0.887). Multivariate analysis showed that RT was significantly associated with a reduction in mortality in the HER2(-) group (hazard ratio, 0.738; 95% confidence interval, 0.549-0.993; p=0.045). CONCLUSION: We found that postoperative RT was not associated with a survival benefit in HER2(+) breast cancer patients, suggesting that HER2(+) breast cancers could be RT resistant.

Reduction in thermal conductivity of Bi thin films with high-density ordered nanoscopic pores.

We prepared two-dimensional Bi thin films with high-density ordered nanoscopic pores by e-beam evaporation of Bi metal. For this structure, we used polystyrene beads ranging from 200 to 750 nm in diameter as an etch mask. The typical hole and neck sizes of the Bi thin films with approximately 50 nm in thickness on SiO2/Si substrates were in the range of 135 to 490 nm and 65 to 260 nm, respectively. By measuring the thermal characteristics through a 3ω technique, we found that the thermal conductivities of nanoporous Bi thin films are greatly suppressed compared with those of corresponding bulk materials. With a decrease in pore size to approximately 135 nm, the thermal conductivity decreased significantly to approximately 0.46 W/m·K at 300 K.

Thermal conductivity measurements of single-crystalline bismuth nanowires by the four-point-probe 3-ω technique at low temperatures.

We have successfully investigated the thermal conductivity (κ) of single-crystalline bismuth nanowires (BiNWs) with [110] growth direction, via a straightforward and powerful four-point-probe 3-ω technique in the temperature range 10-280 K. The BiNWs, which are well known as the most effective material for thermoelectric (TE) device applications, were synthesized by compressive thermal stress on a SiO2/Si substrate at 250-270 °C for 10 h. To understand the thermal transport mechanism of BiNWs, we present three kinds of experimental technique as follows, (i) a manipulation of a single BiNW by an Omni-probe in a focused ion beam (FIB), (ii) a suspended bridge structure integrating a four-point-probe chip by micro-fabrication to minimize the thermal loss to the substrate, and (iii) a simple 3-ω technique system setup. We found that the thermal transport of BiNWs is highly affected by boundary scattering of both phonons and electrons as the dominant heat carriers. The thermal conductivity of a single BiNW (d ~ 123 nm) was estimated to be ~2.9 W m(-1) K(-1) at 280 K, implying lower values compared to the thermal conductivity of the bulk (~11 W m(-1) K(-1) at 280 K). It was noted that this reduction in the thermal conductivity of the BiNWs could be due to strongly enhanced phonon-boundary scattering at the surface of the BiNWs. Furthermore, we present temperature-dependent (10-280 K) thermal conductivity of the BiNWs using the 3-ω technique.

Reliability of reconstructed breast flap after chemotherapy and radiotherapy in immediate breast reconstruction.

BACKGROUND: Postmastectomy adjuvant therapy is used to prevent locoregional recurrence and improve overall breast cancer specific survival rates. However, it can adversely affect the cosmetic results of reconstruction. Therefore, the authors examined flap stability and patients' satisfaction with immediate breast reconstruction after adjuvant therapy. METHODS: We retrospectively reviewed the medical records of 204 patients from January 2006 to November 2011. For complication rates, the authors categorized the patients who underwent the immediate breast reconstruction into 4 groups: adjuvant chemotherapy and radiotherapy group, adjuvant chemotherapy only group, adjuvant radiotherapy only group, and the group that did not undergo adjuvant therapy. For comparison of patients' satisfaction, the study was performed with an additional 16 patients who had undergone delayed breast reconstruction. RESULTS: Regarding complication rates, the group that had undergone adjuvant therapy showed no significant difference compared to the group that did not undergo adjuvant therapy. In evaluating the patients' satisfaction, there was no significant difference. CONCLUSIONS: Even after adjuvant therapy, immediate breast reconstruction showed good results with respect to flap stability and patients' satisfaction. Immediate breast reconstruction and adjuvant therapy is a safe and useful option for breast cancer patients.

Quantitative DNA methylation and recurrence of breast cancer: a study of 30 candidate genes.

BACKGROUND: The need for new prognostic factors in breast cancer is ever increasing as breast cancer management evolves. Aberrant DNA methylation plays a pivotal role in cancer development and progression; DNA methylation-based biomarkers may provide independent prognostic information. We used pyrosequencing to investigate the prognostic potential of quantitative DNA methylation of a large set of candidate genes in a Korean single-institution series of operable breast cancer. METHODS: Absolute DNA methylation in 20 candidate genes from an initial set of 30 genes was measured by pyrosequencing of bisulfite converted DNA in 121 fresh frozen breast cancer cases. Survival analyses used continuous and categorized (quintile-based) gene methylation data with time to recurrence (TTR) as an endpoint. Prognostic abilities of gene-only and risk-score models were explored. RESULTS: Median follow-up was 5.1 years; 25 recurrences (21%) were observed. Nodal status, methylation of TWIST1, SLIT2 (both as continuous and categorized variables) and APC, HLA-A, NKX2-5, SERPINB5, SFN (as categorized variables) were significantly prognostic; grade showed a prognostic trend. A multivariate model containing nodal status, grade and TWIST1 was a best fit (p< 0.001) in stepwise regression; risk-score based on this model separated patients into 3 distinct risk-groups (p< 0.001). A gene-only model based on TWIST1 and SFN also classified patients into distinct risk-groups (p=0.009). CONCLUSIONS: This study shows that accurate quantitative measurement of DNA methylation by pyrosequencing identifies a small set of genes with independent prognostic potential in breast cancer. These genes complement the current clinico-pathological prognostic factors and appear to be potential biomarkers that warrant further validation.

Lessons learned from 100 initial cases of laparoscopic liver surgery.

PURPOSE: Laparoscopic liver resection (LLR) is now widely accepted and is being increasingly performed. The present study describes our experience with LLR at a single center over an eight-year period. METHODS: This retrospective study enrolled 100 patients between October 2002 and February 2010. Forty-six benign lesions and 54 malignant lesions were included. The LLR performed included 58 pure laparoscopy procedures, 18 hand-assisted laparoscopy procedures and 24 hybrid technique procedures. RESULTS: The mean age of the patients was 57 years; among these patients, 31 were over 65 years of age. The mean operation time was 220 minutes. The overall morbidity was 11% and the mortality was zero. Among the 20 patients with simple hepatic cysts, 50% unexpectedly recurred. Among the 41 patients with hepatocellular carcinoma, 21 patients (51%) underwent preoperative radiofrequency ablation therapy or transarterial chemoembolization. During parenchymal-transection, 11 received blood transfusion. The width of the resection margins was under 0.5 cm in 11 cases (27%); 0.5 to 1 cm in 22 cases (54%) and over 1 cm in eight cases (12%). There was no port site seeding, but argon beam coagulation-induced tumor dissemination was observed in two cases. The overall two-year survival rate was 75%. CONCLUSION: This study suggests that the applications for LLR can be gradually expanded when assuring that the safety and curability of LLR are equivalent to that of open liver resection.

Laparoscopic splenectomy for sclerosing angiomatoid nodular transformation of the spleen.

Primary splenic tumors are rare and mainly found incidentally on radiologic studies. Among them, sclerosing angiomatoid nodular transformation (SANT) of the spleen is a new entity defined as a benign pathologic lesion. Most SANTs have no clinical symptoms and are occasionally accompanied by other splenic diseases such as malignancies. So, the exact diagnosis of the nature of the splenic tumor is mandatory for further treatment. But, preoperative diagnosis is not easy since it is difficult to obtain the tissue from the spleen for pathological study. Recently, laparoscopic splenectomy has become the more standard procedure for the spleen for diagnosis and treatment. Here, we report a rare case of SANT diagnosed following laparoscopic splenectomy.

Application of an endo-GIA for ligation of the cystic duct during difficult laparoscopic cholecystectomy.

BACKGROUND/AIMS: Laparoscopic cholecystectomy has become the gold standard modality for treating gallbladder disease. There are many techniques for the ligation of a dilated and inflamed cystic duct. The aim of this study is to assess the efficacy and applicability of an Endo-GIA for dilated cystic duct ligation. METHODOLOGY: From October 1992 to September 2009, 3413 patients underwent laparoscopic cholecystectomy for gallbladder disease at the Dong-A Medical Center, and 92 (2.7%) patients' cystic ducts were ligated by an Endo-GIA. We retrospectively analyzed these 92 cases. RESULTS: The cystic ducts were successfully ligated with an Endo-GIA in 88 patients. Four patients required conversion to open surgery. The mean operation time was 111.9 minutes. The mean length of the hospital stay was 4.1 days. Postoperative complication occurred in 16 patients (17%). The follow-up period ranged from 0.5 to 75 months. CONCLUSIONS: Endo-GIA is safe and feasible. Postoperative complication occurred in 16 patients after application of an Endo-GIA. However, those complications were successfully managed by conservative treatment. The rate of complications was comparable to the best results from most of the large series in the West. Therefore, using an Endo-GIA could be attempted in carefully selected patients with difficult cases of laparoscopic cholecystectomy.