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.

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.

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.

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.