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Context The upregulation of TRIB3 (Tribbles homolog 3), a stress-inducible gene encoding a pseudokinase, has been implicated in the development of insulin resistance in the skeletal muscle and liver of patients with obesity and type 2 diabetes. However, there is little information regarding TRIB3 expression in human adipose tissue. Objective To investigate whether TRIB3 expression is dysregulated in human adipose tissue in the context of obesity and type 2 diabetes and whether TRIB3 expression in adipose tissues is associated with insulin resistance. Methods We measured metabolic parameters and TRIB3 expression in abdominal subcutaneous and visceral adipose tissue in obese (with or without type 2 diabetes) and normal-weight women. Regulation of TRIB3 expression was studied in human adipocytes. Results TRIB3 expression in both fat depots was higher in patients with obesity and/or type 2 diabetes; in addition, the expression level was significantly associated with insulin resistance. Incubating adipocytes under conditions mimicking the microenvironment of obese adipose tissue, including increased endoplasmic reticulum (ER) stress, induced TRIB3 expression. In human adipocytes, the overexpression of TRIB3 impaired insulin-stimulated protein kinase B (AKT) phosphorylation and caused dysregulation of the transcription of genes encoding bioactive molecules released from adipocytes, such as proinflammatory cytokines, adiponectin, and leptin. Pioglitazone, an insulin-sensitizing agent, reduced both these effects of TRIB3 and the ER stressor–induced expression of TRB3. Conclusion Our data indicate that TRIB3 expression in adipose tissue is enhanced in patients with obesity and suggest that increased TRIB3 dysregulates adipocyte function, which may contribute to the development of insulin resistance.

Endoscopic sampling is essential for tissue diagnosis of cholangiocarcinoma (CCA). To evaluate and compare the diagnostic sensitivities of endoscopic retrograde cholangiopancreatography-guided brush cytology biopsy, and endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) in patients with CCA. A comprehensive literature search through multiple databases was conducted for articles published between January 1995 and August 2020. The pooled rates of sensitivity for the diagnosis of CCA and of adverse events were compared among brushing, biopsy, brushing & biopsy, and EUS-FNA. In total, 1123 patients with CCA (32 studies), 719 patients (20 studies), 358 patients (13 studies), and 422 patients (17 studies) were tested by brushing, biopsy, brushing & biopsy, and EUS-FNA, respectively. The pooled diagnostic sensitivity was 56.0% (95% confidence interval (CI) 48.8–63.1%, I2 = 83.0%) with brushing, 67.0% (95% CI 60.2–73.5%, I2 = 72.5%) with biopsy, 70.7% (95% CI 64.1–76.8%, I2 = 42.7%) with brushing & biopsy, and 73.6% (95% CI 64.7–81.5%, I2 = 74.7%) with EUS-FNA. The diagnostic sensitivity was significantly lower for brushing than for biopsy, brushing & biopsy, or EUS-FNA. No significant difference was noted in diagnostic sensitivities among biopsy, brushing & biopsy, and EUS-FNA. Adverse events were comparable between the groups. Intraductal biopsy, brushing & biopsy, and EUS-FNA had comparable efficacy and safety for the diagnosis of CCA. Brushing was the least sensitive diagnostic tool compared with intraductal biopsy or EUS-FNA. Given the modest diagnostic sensitivities of intraductal biopsy and EUS-FNA in the diagnosis of CCA, further studies for complementing these techniques with biomarkers may be needed.

Background: We evaluated the efficacy and safety of gemcitabine in combination with erlotinib and S-1 for the treatment of advanced pancreatic cancer. Methods: Chemotherapy-naïve patients with pathologically-proven locally advanced, recurrent, or metastatic pancreatic adenocarcinoma were assessed for eligibility. Gemcitabine was administered at 1,000 mg/m2 intravenously on days 1 and 8, erlotinib was administered at 100 mg/day on days 1-21, and S-1 was administered at 60 mg/m2 on days 1-14 every 21 days and continued to a maximum of 8 cycles of treatment. Dose escalation of S-1 to 80 mg/m2 was permitted from the second cycle for pre-defined tolerable patients. Results: Thirty-seven patients (median age 61.5 years) were enrolled. A total of 140 cycles of chemotherapy were administered (median of 3.8; range 1-8 cycles). Toxicities were evaluated in 36 patients, and the responses were evaluated in 32 patients. Major grade 3/4 toxicities included neutropenia (25%), febrile neutropenia (2.8%), fatigue (22.2%), infection (8.3%), vomiting (5.6%), and mucositis (5.6%). The confirmed overall response rate was 12.5% [95% confidence interval (CI), 5.1-28.9%] and the disease control rate was 71.9% (95% CI, 56.8-86.3%). The median progression-free survival and overall survival were 3.7 months (95% CI, 2.8-4.6 months) and 6.7 months (95% CI, 3.4-9.9 months), respectively. Conclusion: The combination of gemcitabine, erlotinib, and S-1 provided an acceptable toxicity profile and modest clinical benefits in patients with advanced pancreatic cancer.

Study Objective To investigate the prognostic factors and impact of minimally invasive surgery (MIS) in surgically treated early-stage high-grade (HG) neuroendocrine cervical carcinoma (NECC). Design Retrospective cohort study. Setting Asan Medical Center, Seoul, Korea. Patients Patients with International Federation of Obstetrics and Gynecology (2009) stages IB1 to IIA HG NECC. Interventions All patients underwent radical hysterectomy (RH) with a laparotomy or an MIS approach. Measurements and Main Results Between 1993 and 2017, 47 patients with International Federation of Obstetrics and Gynecology stages IB1 to IIA1 HG NECC were initially treated with RH. Clinicopathologic variables of patients were retrospectively reviewed from electronic medical records. The median follow-up period was 28.2 months (interquartile range, 17.1–42). Stage IB1 disease was the most common (70.2%). Twenty-nine patients (61.7%) underwent RH by MIS. The overall survival (OS) and disease-free survival (DFS) rates were 63.8% and 38.3%, respectively. Lymph node metastasis and resection margin involvement were significant risk factors for DFS (hazard ratio [HR], 2.227; 95% confidence interval [CI], 1.018–4.871; p =.045 and HR, 6.494; 95% CI, 1.415–29.809; p =.016, respectively) and OS (HR, 3.236; 95% CI, 1.188–8.815; p =.022 and HR, 12.710; 95% CI, 1.128–143.152; p =.040, respectively). The Kaplan-Meier survival curves revealed no significant differences in OS and DFS between the laparotomy and MIS groups (50% vs 72.4% log-rank p =.196, 38.9% vs 37.9% p =.975). Conclusion Lymph node metastasis and resection margin involvement were poor prognostic factors of survival outcomes in initially surgically treated early-stage HG NECC. No difference was observed in the survival outcomes between the MIS and laparotomy approaches.

ObjectivesStaging procedure in borderline ovarian tumors is a topic of controversy. Upstaging in non-serous borderline ovarian tumors that are confined to the ovary is rare. The aim of this study was to assess the impact of surgical staging on clinical outcomes in mucinous borderline ovarian tumors.MethodsThis was a retrospective study conducted at the Asan Medical Center, Seoul, Korea between January 1990 and December 2015, that included 432 patients with mucinous borderline ovarian tumors and at least 6 months follow-up. These patients were divided into a ‘staging group’ and ‘unstaged group’. The staging group referred to patients who, in addition to hysterectomy and/or adnexal surgery, underwent at least one of the following: cytology, omental biopsy/omentectomy, peritoneal biopsy, lymph node biopsy/lymphadenectomy, or appendectomy. The unstaged group referred to patients who did not undergo any staging procedure but underwent adnexal surgery (cystectomy or oophorectomy).ResultsMedian patient age was 40 (range 9–87) years. A total of 367 patients (85%) underwent a staging procedure (staging group) and 65 (15.0%) patients did not (unstaged group). Among the staging group, 258, 4, 100, and 5 patients were FIGO stage IA, IB, IC, or II-III, respectively. Overall recurrence was confirmed in 15 patients and median time to recurrence was 13.4 (range 0.4–127.3) months. One patient was in the unstaged group and had borderline recurrence. Fourteen were in the staging group, and 11 of them had borderline and three had invasive recurrence. Extraovarian disease was found at recurrence only in two patients. There was no significant difference in recurrence-free survival (p=0.39) and in overall survival between the staging group and the unstaged group (p=0.40). In total, 16 (4.4%) of 367 patients who underwent a staging procedure were upstaged.ConclusionStaging in mucinous borderline ovarian tumors may be omitted if there is no obvious evidence of gross extraovarian disease.

ContextAdrenomedullin 2 (AM2) plays protective roles in the renal and cardiovascular systems. Recent studies in experimental animals demonstrated that AM2 is an adipokine with beneficial effects on energy metabolism. However, there is little information regarding AM2 expression in human adipose tissue.ObjectiveTo investigate the pattern and regulation of the expression of AM2 and its receptor component in human adipose tissue, in the context of obesity and type 2 diabetes.MethodsWe measured metabolic parameters, serum AM2, and expression of ADM2 and its receptor component genes in abdominal subcutaneous and visceral adipose tissue in obese (with or without type 2 diabetes) and normal-weight women. Serum AM2 was assessed before and 6 to 9 months after bariatric surgery. Expression/secretion of AM2 and its receptor were assessed in human adipocytes.ResultsADM2 mRNA in both fat depots was higher in obese patients, whether diabetic or not. Although serum AM2 was significantly lower in obese patients, it was not changed after bariatric surgery. AM2 and its receptor complex were predominantly expressed by adipocytes, and the expression of CALCRL, encoding a component of the AM2 receptor complex, was lower in both fat depots of obese patients. Incubating adipocytes with substances mimicking the microenvironment of obese adipose tissue increased ADM2 mRNA but reduced both AM2 secretion into culture media and CALCRL mRNA expression.ConclusionsOur data indicate that AM2 signaling is suppressed in adipose tissue in obesity, involving lower receptor expression and ligand availability, likely contributing to insulin resistance and other aspects of the pathophysiology associated with obesity.

Objective To investigate the expression of different histone deacetylases and their association with disease characteristics and survival outcomes in uterine leiomyosarcoma patients. Methods The immunohistochemical expression of different histone deacetylases and p53 by tissue microarray and histological subtypes were assessed in tumor tissue samples of 42 eligible patients. Results Histone deacetylases 1–4, 6 and 8 showed prevalent and strong (3+) expression (88.1, 90.5, 95.2, 92.9, 83.3 and 100%, respectively). Histone deacetylases 5, 7 and 9 showed infrequent strong expression (33.3, 50 and 38.1%, respectively). There were trends of higher disease-free survival rates according to the combination of weaker expression of histone deacetylase 5, 7 or 9 with positive p53 expression or with non-epithelial subtype. The patients with triple-positive favorable prognostic factors (any of weaker histone deacetylase 5, 7 and 9 expression, p53 positive, and non-epithelioid subtype) had the better survival outcomes while the patients with other combinations had the worse survival outcomes. In multivariate analysis, histone deacetylase 5 in combination with epithelioid subtype was an independent predictor for disease-free survival. Conclusions Expression of histone deacetylase 5, 7 and 9 is a potential prognostic marker in uterine leiomyosarcoma when combined with pathologically relevant prognostic factors (p53 and histological subtype). This prevalent and strong histone deacetylase expression warrants further study in well-designed investigations of histone deacetylases as therapeutic targets in uterine leiomyosarcoma.

Background: Endoscopic ultrasound (EUS)-guided sampling has been widely used for pathologic diagnosis of pancreatic lesions and intra-abdominal lymphadenopathy. However, its effectiveness for diagnostic decision making in indeterminate radiological diagnosis has not been well determined. Materials and Methods: From March 2012 to October 2015, 98 consecutive patients who underwent EUS-guided FNA for solid intra-abdominal lesions were retrospectively analyzed (100 procedures). The purpose of EUS-guided sampling was classified as (1) confirmation of a high-confidence radiological diagnosis (High-confidence group) or (2) decision making in the differential diagnostic dilemma for indeterminate radiological diagnosis (Indeterminate group). The accuracies of EUS-guided sampling according to the purpose were analyzed and then compared. Results: Of the 100 procedures, 22 procedures (22%) came under the Indeterminate group, whereas 78 came under the High-confidence group. The accuracies did not differ between the Indeterminate and the High-confidence groups (86.4% vs. 88.5%, p = 1.000). Clinical conditions that required EUS-guided sampling for indeterminate radiological diagnosis were (1) pancreatic cancer vs. benign disease (n = 8, e.g., pancreatic cancer vs. mass-forming pancreatitis), (2) recurrence of previous/pre-existing cancer vs. benign disease (n = 5, e.g., recurrent gastric cancer vs. reactive lymph node), (3) pathologic differentiation of presumed malignancy (n = 6, e.g., lymphadenopathies in the previous history of esophageal cancer and colon cancer), or (4) miscellaneous (n = 3, e.g., tuberculous lymphadenopathy vs. other condition). Conclusions: EUS-guided sampling demonstrated an accuracy of 86.4% in the clinical setting of indeterminate radiological diagnosis, which was not different from that of the confirmation of high-confidence diagnosis.

The aim of this study is to analyze the correlation between clinically significant histologic results and HPV in women with AGC in pap test. Of the 311 women confirmed as AGC, 111 women (35.7%) was identified as positive for HPV. In the AGC analysis, cervical lesions were significantly more common in HPV positive group compared to HPV negative group (61.2% vs. 10.5%, p < 0.001). In contrast, endometrial lesions were not associated with HPV infection (8.1% vs. 4.5%, p = 0.12). The HPV-DNA testing in women with AGC may be a useful tool for predicting clinically significant cervical lesions.

Background Terminal ileal (TI) ulcers are occasionally detected in asymptomatic individuals and mostly resolve without any treatment. In patients with ulcerative colitis (UC), TI ulcers are infrequently observed without evidence of backwash ileitis. However, the clinical significance and natural course of the lesions are unclear. The aim of our study was to evaluate the frequency and clinical implications of TI ulcers in patients with UC. Methods We retrospectively reviewed 397 patients with UC via successful TI intubation during colonoscopy. We compared the clinical characteristics of patients manifesting TI ulcers with those who did not. The natural course of TI lesions was also investigated during the follow-up periods. Results Forty-one patients (10.3%) showed TI ulcers without evidence of inflammation in the right colon. The patients with and without TI ulcers were not different in terms of baseline characteristics, disease activity and extent at the time of the UC diagnosis, proximal extension, Mayo endoscopic score at the last endoscopic examination, medication history, UC-related hospitalization, and relapse during follow-up periods. Of the 30 patients who underwent follow-up colonoscopy in patients with TI ulcers, 23 (76.7%) showed resolution of TI ulcer. In addition, patients with remaining TI ulcers did not differ in disease activity and biopsy results compared with those with resolving TI ulcers. Conclusions Discrete TI ulcers are more common in patients with UC, compared with the healthy cohort. No significant clinical impact on disease extension and severity is found.

Background The indications for maintenance glucocorticoid therapy (MGT) and its duration after initial remission of type 1 autoimmune pancreatitis (AIP) remain controversial. In contrast to the Japanese treatment protocol, the Mayo protocol does not recommend MGT after initial remission. This study aimed to evaluate the relapse rate in patients with type 1 AIP according to the duration of glucocorticoid therapy. Methods We conducted a systematic literature review up until November 30, 2020, and identified 40 studies reporting AIP relapse rates. The pooled relapse rates were compared between groups according to the protocol and duration of glucocorticoids (routine vs. no MGT; glucocorticoids ≤6 months vs. 6–12 months vs. 12–36 months vs. ≥ 36 months). The pooled rates of adverse events related to glucocorticoids were also evaluated. Results Meta-analysis indicated calculated pooled relapse rates of 46.6% (95% confidence interval (CI), 38.9–54.3%) with glucocorticoids for ≤ 6 months, 44.3% (95% CI, 38.8–49.8%) for 6–12 months, 34.1% (95% CI, 28.6–39.7%) for 12–36 months, and 27.0% (95% CI, 23.4–30.6%) for ≥ 36 months. The rate of relapse was also significantly lower in patients with routine-use protocol of MGT (31.2%; 95% CI, 27.5–34.8%) than in patients with no MGT protocol (44.1%; 95% CI, 35.8–52.4%). Adverse events were comparable between groups. Conclusions The rate of relapse tended to decrease with extended durations of glucocorticoid therapy up to 36 months. Clinicians may decide the duration of glucocorticoids according to patient condition, including comorbidities and risk of relapse.

The lymph node status is the most important prognostic factor for endometrial cancer. This study aimed to assess whether sentinel lymph node mapping (SLNM) is applicable in endometrial cancer. A retrospective review of patients with endometrial cancer who were diagnosed and treated in Asan Medical Centre from September 2015 to December 2017 was conducted. One hundred patients underwent robotic (da Vinci®) or laparoscopic surgical treatment, including SLNM with indocyanine green (ICG) fluorescence detection using the Firefly® and NIR/ICG systems. At least one lymph node area was observed in 100% of SLNM cases. Sentinel node detection and frozen biopsy were performed in all cases, and all patients with metastasis were found on SLNM. The sensitivity and negative predictive value were both 100% in the patient-by-patient and station-by-station analyses. SLNM appears to be a feasible method to reduce the morbidity and increase the detection rate in early-stage endometrial carcinoma.What is already known on this subject? There are studies that it is safe to diagnose the possibility of lymph node metastasis through sentinel lymph node mapping in endometrial cancer.What do the results of this study add? In this study, it is shown that the accuracy of sentinel lymph node mapping is 100% accurate.What are the implications of these findings for clinical practise and/or further research? Therefore, total lymphadenectomy will not be necessary for the future.

We aimed to investigate the effectiveness of continuing medical therapy in patients who did not achieve complete response (CR) despite 9 months of progestin treatment. We also sought to determine the prognostic factors associated with achieving CR among these patients.We retrospectively analyzed 51 patients with presumed stage IA, grade 1 or 2 endometrioid adenocarcinoma who had persistent disease on biopsy performed at 9-12 months after at least 9 months of progestin-based therapy. Data on clinicopathological factors and oncological and obstetrical outcomes following continuous hormonal treatment were extracted from the patients' medical records and analyzed. Univariate and multivariate analyses for predicting CR were performed.Thirty-seven (72.5%) of 51 patients achieved CR after prolonged fertility-sparing treatment. Median time to CR from starting initial progestin was 17.3 months (range, 12.1-91.7 months). On univariate analysis, history of polycystic ovarian syndrome, histologic grade 2, and not achieving partial response (PR) until 12 months were significantly associated with failure to CR (odds ratio [OR], 6.188, 95% confidence interval [CI], 1.405-27.244, p = 0.018; OR, 9.722, 95% CI, 1.614-58.581, p = 0.013; and OR, 21.750, 95% CI, 4.016-117.783, p 0.001, respectively). Multivariate analysis revealed that not achieving PR until 12 months was an independent prognostic factor predicting failure to CR after prolonged progestin therapy (OR, 21.803, 95% CI, 3.601-132.025, p = 0.001).Continued medical treatment is effective for persistent early endometrial carcinoma after at least 9 months of progestin therapy in young women who want to preserve their fertility.

OBJECTIVE We investigated the feasibility and safety of fertility-sparing surgery (FSS) in patients with epithelial ovarian cancer (EOC) with dense adhesions. METHODS Patients were divided into cases with and without dense adhesions in this retrospective study. RESULTS Of the 95 eligible patients, 29 patients had dense adhesions. Mean age, proportion of staging procedure, distribution of histologic type, and co-presence of endometriosis were different (p=0.003, 0.033, 0.011, and 0.011, respectively). The median follow-up period was 57.8 (0.4-230.0) months. There were no differences in the rates of recurrence (21.2% vs. 20.7%, p=1.000) or death (16.7% vs. 6.9%, p=0.332) between the 2 groups. There was no difference in the pattern of recurrence or in disease-free survival (DFS) and overall survival (OS) between the 2 groups. In multivariate analysis, pretreatment cancer antigen-125 >35 U/mL and International Federation of Gynecology and Obstetrics stage IC were significant factors of worse DFS and OS, while dense adhesion was not a prognostic factor for both DFS (hazard ratio [HR]=0.9; 95% confidence interval [CI]=0.3-2.7; p=0.792) and OS (HR=0.2; 95% CI=0.1-1.8; p=0.142), nor were age, proportion of staging procedure, histologic type, and co-presence of endometriosis. Moreover, the distribution of those 2 significant prognostic factors was not different between the 2 groups. Dense adhesions were subgrouped into non-tumor and tumor associated dense adhesions for further analysis and the results were same. CONCLUSION FSS is feasible and safe in EOC, regardless of the presence of dense adhesions.

Background: We aimed to evaluate the clinical implication of circulating tumor cell (CTC) counts in correlation with prognosis and radiologic/pathologic response to therapy in locally advanced breast cancer patients undergoing preoperative systemic therapy. Methods: From Feb 2014 to May 2017, 207 patients without distant metastasis were prospectively enrolled from AMC. CTC counts were analyzed before-during-after the therapy. CTC isolation was performed using a SMART BIOPSY™ SYSTEM Isolation kit (Cytogen, Inc., Seoul, Korea). Recurrence-free and overall survival was analyzed according to CTC counts. Result: The mean follow-up period was 22.46 months and mean age was 46.48 years. One or more CTC was identified in 132 of 203 patients(65.0%) before NST, in 135 of 186 patients(72.0%) during NST and 103 of 171 patients(60.2%) after NST. Initial tumor burden at diagnosis -tumor size, lymph node metastasis- was not correlated with CTC positivity. Overall, CTC count ((≥1 CTC, ≥2 CTCs, and ≥5 CTCs) was not correlated with response to therapy. Using RECIST criteria, 86.5% (179/204) were responders (complete, partial response, CR/PR) and 12.1% (25/204) were non-responders (stable, progressive disease, SD/PD). 14.5% (30/207) showed a pathologic complete response (pCR), yet no association was found between CTC count/changes and radiologic/pathologic response to therapy. Also, CTC count was not correlated with prognosis among the whole population. However, HR+ tumors, CTC detection before NST was significantly associated with treatment response by RECIST criteria (responder vs. non-responder) (p=0.003, p=0.017 and p=0.023, respectively). Conclusions: Our findings support limited value of CTC count for locally advanced breast cancers undergoing neoadjuvant systemic therapy. Citation Format: Gwark S-C, Kim J, Kim YH, Kim MS, Park JY, Lee SB, Sohn G, Chung IY, Ko BS, Kim HJ, Lee JW, Son BH, Ahn SH. Analysis of serial circulating tumor cell count during neoadjuvant systemic therapy in breast cancer patients [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P6-09-09.

Background: Mucinous carcinoma of the breast is a rare type of breast cancer with favorable outcome compared with other types of breast cancer. The current guideline does not recommend chemotherapy/anti-HER2 therapy for mucinous breast cancer with hormone receptor-positive subtype regardless of HER2/neu status. In this study, we evaluated the survival of pure mucinous breast cancer according to tumor stage and subtype. Methods: Between 1989 and 2014, in Asan Medical Center, Korea, total 473 pure mucinous carcinomas (stage I-III) undergone curative surgery were reviewed retrospectively. 5yr disease-free and overall survival were analyzed according to size, lymph node metastasis, hormone receptor/HER2 status and given therapy. Result: Total of 473 patients with pure mucinous breast cancer were analyzed and median follow-up duration was 78.00 months. 439 patients were hormone receptor-positive, 374 were node negative, 55 were HER2/neu positive. Among 374 patients with hormone receptor-positive and node-negative, tumor size was Overall, 5-year disease-free survival (DFS) rate was 94.1% and the 5-year overall survival (OS) rate was 95.9%. Using Cox regression analysis, lymph node metastasis was the only significant prognostic factor for both DFS (HR4.0, 95%CI:1.8-9.0, p=0.001) and OS (HR3.5, 95%CI:1.3-8.9, p=0.008). Among HR-positive/node-negative with tumor size ≥3cm, HER2/neu positivity was only significantly associated with 5yr-DFS (71.4% in HER2/neu+ vs. 96.4% in HER2/neu-, HR9.5, 95%CI:1.3-67.5, p=0.024). This observation was consistently combining both 'HR-positive/node-negative/>3cm' and 'HR-positive/node positive' BCs (N=127) that HER2 positive tumors showed worse survival (HR 3.7, 95%CI:1.2-10.8, p=0.015). Intriguingly, within this subgroup of HR-positive/node-negative/>3cm' and 'HR-positive/node positive' BCs, among HER2 positive tumors, while 5yr-DFS was 63.7% in patients who didn't receive trastuzumab, 100% were disease free in patients who were given trastuzumab. Conclusions: Overall, nodal status was the most significant prognostic factor for pure mucinous breast cancer. In hormone receptor-positive, lymph node negative mucinous breast cancer with tumor of ≥3cm, HER2 positive BCs showed worse survival, suggesting a potential role of anti-HER2 strategy in this subgroup. Citation Format: Gwark S-C, Lee JW, Lee SB, Sohn G, Kim J, Chung IY, Ko BS, Kim HJ, Son BH, Ahn SH. Clinical implication of HER2/neu status in hormone receptor positive pure mucinous breast cancer [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P2-08-22.

Background The diagnosis of autoimmune pancreatitis (AIP) remains challenging, especially when serum IgG4 is normal or imaging features are indeterminate. We performed a systematic review and meta-analysis to evaluate the performance of IgG4 immunostaining of pancreatic, biliary, and ampullary tissues as a diagnostic aid for AIP. Methods A comprehensive literature search of the PubMed, EMBASE, and Ovid MEDLINE databases was conducted until February 2020. The methodological quality of each study was assessed according to the Quality Assessment of Diagnostic Accuracy Studies checklist. A random-effects model was used to summarize the diagnostic odds ratio and other measures of accuracy. Results The meta-analysis included 20 studies comprising 346 patients with AIP and 590 patients with other pancreatobiliary diseases, including 371 pancreatobiliary malignancies. The summary estimates for tissue IgG4 in discriminating AIP and controls were as follows: diagnostic odds ratio 38.86 (95% confidence interval (CI), 18.70–80.75); sensitivity 0.64 (95% CI, 0.59–0.69); specificity 0.93 (95% CI, 0.91–0.95). The area under the curve was 0.939 for tissue IgG4 in discriminating AIP and controls. Subgroup analysis revealed no significant difference in diagnostic accuracy according to control groups (pancreatobiliary cancer versus other chronic pancreatitis) and sampling site (pancreas versus bile duct/ampulla). Conclusions Current data demonstrate that IgG4 immunostaining of pancreatic, biliary, and ampullary tissue has a high specificity but moderate sensitivity for diagnosing AIP. IgG4 immunostaining may be useful in supporting a diagnosis of AIP when AIP is clinically suspected, but a combination of imaging and serology does not provide a conclusive diagnosis.

BACKGROUND Gastric ‘indefinite for neoplasm/dysplasia’ (IFND) is a borderline lesion that is difficult to diagnose as either regenerative or neoplastic. There is a need for guidance in the identification of a subset of patients, who have an IFND lesion with a higher risk of malignant potential, to enable risk stratification and optimal management. AIM To determine the clinical and pathologic factors for the accurate diagnosis of gastric IFND lesions. METHODS In total, 461 gastric lesions diagnosed via biopsy as IFND lesions were retrospectively evaluated. Endoscopic resection (n = 134), surgery (n = 22), and follow-up endoscopic biopsy (n = 305) were performed to confirm the diagnosis. The time interval from initial biopsy to cancer diagnosis was measured, and diagnostic delays were categorized as > 2 wk, > 2 mo, > 6 mo, and > 1 year. The IFND lesions presenting as regenerating atypia (60%) or atypical epithelia (40%) at initial biopsy were adenocarcinomas in 22.6%, adenomas in 8.9%, and gastritis in 68.5% of the cases. RESULTS Four clinical factors [age ≥ 60 years (2.445, 95%CI: 1.305-4.580, P = 0.005), endoscopic size ≥ 10 mm (3.519, 95%CI: 1.891-6.548, P < 0.001), single lesion (5.702, 95%CI: 2.212-14.696, P < 0.001), and spontaneous bleeding (4.056, 95%CI: 1.792-9.180, P = 0.001)], and two pathologic factors [atypical epithelium (25.575, 95%CI: 11.537-56.695, P < 0.001], and repeated IFND diagnosis [6.022, 95%CI: 1.822-19.909, P = 0.003)] were independent risk factors for gastric cancer. With two or more clinical factors, the sensitivity and specificity for carcinoma were 91.3% and 54.9%, respectively. Ten undifferentiated carcinomas were initially diagnosed as IFND. In the subgroup analysis, fold change (5.594, 95%CI: 1.458-21.462, P = 0.012) predicted undifferentiated or invasive carcinoma in the submucosal layers or deeper. Diagnostic delays shorter than 1 year were not associated with worse prognoses. Extremely well-differentiated adenocarcinomas accounted for half of the repeated IFND cases and resulted in low diagnostic accuracy even on retrospective blinded review. CONCLUSION More than two clinical and pathologic factors each had significant cut-off values for gastric carcinoma diagnosis; in such cases, endoscopic resection should be considered.

The aim of this study is to determine the rate of clinically significant histopathologic lesions in women identified with atypical glandular cells (AGC). Five-hundered and forty patients with AGC, from a cohort of 1013 with AGC, met inclusion criteria for this study by having a proper histologic evaluation. Clinically significant histologic results were obtained in 170 cases with AGC (31.5%). Of the 170 clinically significant cases, 86 of 540 (15.9%) were diagnosed with malignant lesions. The findings of clinically significant lesions in more than 30% of patients support the recommendation that women identified with AGC require extensive histologic examination.

Direct oral anticoagulants (DOACs) are effective in the prevention and treatment of thromboembolism; however, they are associated with upper gastrointestinal bleeding (UGIB). In this study, we evaluated the efficacy of gastroprotective agents (GPAs) in reducing the risk of UGIB in patients receiving DOACs.We retrospectively reviewed the medical records of 2076 patients who received DOACs for the prevention or treatment of thromboembolic events between January 2008 and July 2016. A cumulative incidence analysis using the Kaplan-Meier method was performed to determine the rate of UGIB and its association with GPAs administration.Of the 2076 patients, 360 received GPAs. Over the follow-up period (1160 person-years), one patient in the GPA group (0.7 per 100 person-years) and 29 patients in the non-GPA group (2.8 per 100 person-years) developed UGIB (p = .189). In the multivariate analysis, UGIB was associated with older age (hazard ratio (HR), 1.041; p = .048), a history of peptic ulcer or UGIB (HR, 5.931; p .001), and concomitant use of antiplatelet agents (HR, 3.121; p = .014). GPAs administration did not reduce the risk of UGIB (p = .289). However, based on the subgroup analysis of 225 patients with concomitant use of antiplatelet agents or a history of peptic ulcer or UGIB, the GPA group (0 per 100 person-years) showed reduced incidence of UGIB compared with the non-GPA group (11.3 per 100 person-years) (p = .065).The prophylactic use of GPAs could reduce the risk of UGIB in patients receiving DOACs who have risk factors, such as concomitant use of antiplatelet agents or a history of peptic ulcer or UGIB.

ObjectivesThe aim of this study was to compare surgical and oncologic outcomes of open and laparoscopic surgery in patients with borderline ovarian tumors (BOTs).Materials and MethodsThis study included patients with BOTs who underwent open (n = 433) or laparoscopic (n = 210) surgery between 1990 and 2015. Surgical outcomes, perioperative morbidity, and disease-free survival and overall survival were compared.ResultsThere was no significant difference in age, histologic type of tumor, and laterality of tumor. However, body mass index was slightly higher for the open surgery group (P = 0.046). The open surgery group had a higher serum cancer antigen 125 level (P < 0.001), larger tumor size (P < 0.001), more frequent radical surgery (P = 0.001), higher stage (P = 0.034), and higher incidence of invasive implants (P = 0.035). The operative time (P < 0.001), time interval to return of bowel movement (P < 0.001), and length of postoperative hospital stay (P < 0.001) were significantly shorter and estimated blood loss was significantly less (P < 0.001) in the laparoscopic group. Perioperative complications were documented in 5 (2.4%) patients in the laparoscopic surgery group and 17 (3.9%) in the open surgery group (P = 0.064). Twenty-three (5.3%) patients in the open surgery group and 9 (4.3%) in the laparoscopic surgery group had recurrence (P = 0.902) at a median follow-up of 57 months. The 10-year disease-free survival was 96% and 97% for the open and laparoscopic groups, respectively (P = 0.851), with no significant difference between the groups after adjusting for independent factors (odds ratio, 1.0; 95% confidence interval, 0.4–2.4; P = 0.999). The 10-year overall survival was 99% for both groups, respectively (P = 0.441).ConclusionsLaparoscopic surgery and open surgery showed similar survival outcomes in BOTs. The surgical outcomes of laparoscopic surgery were more favorable.

Immunoglobulin G4-related sclerosing cholangitis (IgG4-SC) is rare disease which is steroid-responsive and often associated with IgG4 related systemic disease such as autoimmune pancreatitis. It is characterized by increased serum IgG4 and IgG4- positive lymphoplasmacytic infiltration in bile ducts. It is often difficult to distinguish IgG4-SC to hilar cholangiocarcinoma if it manifests as an isolated bile duct. We report a case of 79-year-old woman with IgG4-SC which was difficult to distinguish hilar cholangiocarcinoma due to similar clinical and radiologic findings, showing good therapeutic effect after a 2-week steroid trial.

Background Evidence to support the specific use of magnetic resonance tumour regression grade (mrTRG) is inadequate. The aim of this study was to investigate the pathological characteristics of mrTRG after chemoradiotherapy (CRT) for rectal cancer and the implications for surgery. Methods Patients undergoing long-course CRT (45–50 Gy plus a booster dose of 4–6 Gy) for mid or low rectal cancer (cT3−4 or cN+ without metastasis) between 2011 and 2015 who had post-CRT rectal MRI before surgery were included retrospectively. Three board-certified experienced radiologists assessed mrTRG. mrTRG was correlated with pathological tumour regression grade (pTRG), ypT and ypN. In a subgroup of patients with mrTRG1−2 and no tumour spread (such as nodal metastasis) on MRI, the projected rate of completion total mesorectal excision (TME) if they underwent transanal excision (TAE) and had a ypT status of ypT2 or higher was estimated, and recurrence-free survival was calculated according to the operation (TME or TAE) that patients had actually received. Results Some 439 patients (290 men and 149 women of mean(s.d.) age 62·2(11·4) years) were analysed. The accuracy of mrTRG1 for predicting pTRG1 was 61 per cent (40 of 66), and that for ypT1 or less was 74 per cent (49 of 66). For mrTRG2, these values were 22·3 per cent (25 of 112) and 36·6 per cent (41 of 112) respectively. Patients with mrTRG1 and mrTRG2 without tumour spread were ypN+ in 3 per cent (1 of 29) and 16 per cent (8 of 50) respectively. Assuming mrTRG1 or mrTRG1−2 with no tumour spread on post-CRT MRI as the criteria for TAE, the projected completion TME rate was 26 per cent (11 of 43) and 41·0 per cent (41 of 100) respectively. For the 100 patients with mrTRG1–2 and no tumour spread, recurrence-free survival did not differ significantly between TME (79 patients) and TAE (21) (adjusted hazard ratio 1·86, 95 per cent c.i. 0·42 to 8·18). Conclusion Patients with mrTRG1 without tumour spread may be suitable for TAE.

Concurrent presentation of acute hepatitis A virus (HAV) infection and Graves' disease has not been reported in literature worldwide. Although there is no well-established mechanism that explains the induction of Graves' disease by HAV to date, our case suggests that HAV infection may be responsible for inducing Graves' disease. A healthy 27-year-old female presented fever, palpitation, and diarrhea, and she was subsequently diagnosed as acute HAV infection. Concurrently, she showed hyperthyroidism, and the diagnosis was made as Graves' disease. She had never had symptoms that suggested hyperthyroidism, and previous thyroid function test was normal. Acute HAV infection was recovered by conservative management, however, thyroid dysfunction was maintained even after normalization of liver enzymes. Methimazole was used to treat Graves' disease. We report a case of concurrent acute HAV infection and Graves' disease in a patient without preexisting thyroid disease. This suggests that HAV infection may be a trigger for an autoimmune thyroid disease in susceptible individuals.

Background: Mucinous carcinoma of the breast is a uncommon particular type of breast cancer and comprises approximately 4% of all invasive breast cancers. It is charactarized by abundant extracellular mucin production and present a more favorable prognosis than IDC-NOS. Pathologically, mucinous carcinoma is divided into two subtypes : pure and mixed. In this study, we reviewed the clinicopathologic characteristics and prognostic factors of pure mucinous carcinoma. Methods: We reviewed the 23 years cumulative data of pure mucinous breast cancer patients from database of the Breast Cancer Center at ASAN medical center, Korea, between 1989-2011, retrospectively. Total 386 pure mucinous carcinoma cases were reviewed to analyze clinicopathologic characteristics and prognosis. Result: Total of 386 patients with pure mucinous breast cancer were identified. Mean age was 46.7. 149 patients underwent modified radical mastectomy and 236 underwent breast-conserving therapy. The T-stage was T1 in 187 patients, T2 in 178 patients, T3 in 17 patient and T4 in 4 patients. Node negative was 325 and node positive was 61. Estrogen receptor was positive in 342 and negative in 29. Progesterone receptor was positive in 276 and negative in 95. HER-2 was positive in 47 and negative in 273. 152 patients received adjuvant chemotherapy and 240 patients received adjuvant radiotherapy. 351 patients received hormone therapy and among these patients, 231 patients were treated with Tamoxifen alone, 81 were Tamoxifen with ovarian function suppression, 37 were AI only and one patient was ovarian function suppression only. The 5 year disease free survival rate was 93.3%, 5 year cancer specific survival rate was 98.2% and 5 year overall survival rate was 96.6%. Univariate analysis showed that ER status, nodal status and Her2 status were appear to be prognostic factor of Disease free survival rate. Using Cox regression, result of multivariate analysis revealed that only nodal status is the most significant prognostic factor for survival rate. Conclusions: Pure mucinous carcinoma of the breast is a rare subtype with a favorable prognosis. Nodal status rather than ER status, Her2 status are considered to be the most significant prognostic factor of pure mucinos breast cancer. Citation Format: Gwark SC, Lee JW, Lee SB, Sohn G, Kim J, Chung IY, Kim HJ, Ko BS, Son BH, Ahn SH. Clinicopathologic characteristics and prognostic factors of pure mucinous breast cancer [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P1-07-29.

Background and Aims The efficacy of palliative biliary drainage by using bilateral or unilateral self-expandable metal stents (SEMSs) for a malignant hilar biliary stricture (MHS) remains controversial. This prospective, randomized, multicenter study investigated whether bilateral drainage by using SEMSs is superior to unilateral drainage in patients with inoperable MHSs. Methods Patients with inoperable high-grade MHSs who underwent palliative endoscopic insertion of bilateral or unilateral SEMSs were enrolled. The main outcome measurements were the rate of primary reintervention for malfunction after successful placement of SEMSs, stent patency, technical and clinical success rates, adverse events, and survival duration. Results A total of 133 pathology-diagnosed patients were randomized to the bilateral group (n = 67) or the unilateral group (n = 66). The primary technical success rates were 95.5% (64/67) and 100% (66/66) in the bilateral and unilateral groups, respectively ( P = .244). The clinical success rates were 95.3% (61/64) and 84.9% (56/66), respectively ( P = .047). The primary reintervention rates based on the per-protocol analysis were 42.6% (26/61) in the bilateral group and 60.3% (38/63) in the unilateral group ( P = .049). The median cumulative stent patency duration was 252 days in the bilateral group and 139 days in the unilateral group. The risk of stent patency failure was significantly higher in the unilateral group (log-rank test; P P Conclusions Unilateral and bilateral drainage strategies by using SEMSs had similar technical success rates, but bilateral drainage resulted in fewer reinterventions and more durable stent patency in patients with inoperable high-grade MHSs. (Clinical trial registration number: NCT02166970.)

AIM To investigate the clinicopathological variables in early gastric cancer (EGC) patients in relation to differentiation discrepancy. METHODS The data of 265 specimens from 240 patients with EGC, who had undergone radical operation at Hallym University Sacred Heart Hospital from 2010 to 2015, were retrospectively analyzed. We evaluated clinical, endoscopic, and histopathological data according to histological discrepancy. RESULTS Clinically significant discrepancy rate showed the difference in differentiated type (well and moderately differentiated) and undifferentiated type (poorly differentiated and signet ring cell) between endoscopic biopsies and postoperative specimens was 9.4% (25/265). There were no differences in tumor location, size, gross pattern, and number of biopsies. Specimens having histological discrepancy showed more submucosal invasion (72.0% vs 49.6%, P = 0.033) and lymph node involvement (24.0% vs 7.9%, P = 0.009) than specimens having non-discrepancy. The rate of a positive epidermal growth factor receptor status was higher in specimens having discrepancy than in specimens having non-discrepancy (81.0% vs 55.4%, P = 0.035). CONCLUSION The discordance of histologic differentiation is associated with higher submucosal invasion and lymph node metastases in EGC. Patients have histological discrepancy may require additional surgical treatments.

Background Elderly colorectal cancer (CRC) patients tend to avoid standard treatment, especially curative surgical resection, because of concerns about surgical complications or underlying diseases. This study is intended to compare clinical characteristics and prognosis between patients who had undergone surgical resection and received supportive care, and to evaluate the usefulness of surgical treatment in elderly patients. Methods A total of 114 patients aged ≥80 years who were diagnosed with CRC were analyzed retrospectively. Of these patients, 73 patients underwent surgical resection for malignancy and 41 patients received supportive care. Clinicopathological factors and overall survival (OS) rates were compared. Results The s urgical resection group had better Eastern Cooperative Oncology Group (ECOG) performance status, American Society of Anesthesiologists (ASA) physical status, and a lower stage than did the supportive-care group. The 3-year OS rate of the surgical group was significantly higher than that of the supportive-care group (60.7% vs. 9.1%, p < 0.001). In extremely elderly patients (age ≥85 years), the surgical group showed a better 3-year OS rate than did the supportive-care group (73.9% vs. 6.3%, p < 0.001), although ECOG performance status and ASA physical status were not different. The post-operative mortality rate was 4.1%. In the analysis of risk factors related to survival, surgical resection was a good prognostic factor. Conclusions Surgical treatment in elderly CRC patients showed a survival benefit, even in the extremely elderly patients. Surgical resection for CRC in elderly patients can be considered to improve survival.

Objective To identify risk factors for distant recurrence in node-positive cervical cancer patients who underwent radical hysterectomy and pelvic lymph node dissection (PLND) with para-aortic lymph node sampling (PALNS) or para-aortic lymph node dissection (PALND). Methods A total of 299 patients in whom lymph node metastasis was confirmed after radical surgery at Asan Medical Center for stage IA2 to IIB cervical cancer from February 2001 to December 2012 were identified. In all, 72 (24.1%) patients underwent PLND only and 227 (75.9%) underwent PLND with PALNS or PALND. Four patients were excluded due to diagnosed with small cell carcinoma. The clinicopathologic data of 223 patients were retrospectively analyzed. Distant recurrence was defined as recurrence at a site over the pelvic radiation field. Results Among all 223 study patients, the mean number of positive lymph nodes was 4.46. There were 54 (24.2%) patients with distant metastasis. Multivariate analyses using the Cox proportional hazards model showed that histologic types (HR=3.031, P ≤0.001 for adenocarcinoma, HR=2.302, P =0.066 for adenosquamous carcinoma), number of positive lymph nodes (HR=1.077, P ≤0.001), and surgical stage (HR=1.264, P =0.022) were independent risk factors for distant recurrence of cervical cancer. A scoring system for the prediction of distant recurrence was generated by incorporating these factors and showed good discrimination and calibration (concordance index of 0.753). In an internal validation set, this scoring system showed good discrimination with a C-statistics of 0.777. According to the Hosmer-Lemeshow test, the chi-square was 0.650 and the P -value was 0.723. Conclusions We have developed a robust scoring system that can predict the risk of distant recurrence in node-positive cervical cancer patients after radical operation. This scoring system was used to identify a group of patients who required systemic control of distant micrometastasis. This group of patients is an appropriate target for consolidation chemotherapy after concurrent chemoradiation therapy.

Objective The study aims to identify preoperative predictors of complete cytoreduction and early recurrence and death in epithelial ovarian, tubal, and peritoneal cancer after neoadjuvant chemotherapy (NACT). Methods We performed a retrospective analysis of 85 patients who underwent 3 cycles of NACT. Patients were divided into 2 groups according to residual tumor at interval debulking surgery (IDS), and clinicopathologic, surgical, and follow-up data were compared. Results Cancer antigen 125 (CA-125) levels before the IDS after completion of NACT were higher in the residual tumor group (42.0 vs 116.6 U/mL, P = 0.006). The drop rate of CA-125 after NACT was higher in the no residual tumor group (96.8% vs 89.9%, P = 0.001). Patients with residual tumor showed lower disease-free and overall survival outcomes than patients with no residual tumor. In univariate analysis, CA-125 of 100 U/mL or less before IDS and a drop rate after NACT greater than 80% were preoperative predictive factors for complete cytoreduction. In multivariate analysis, a drop rate of CA-125 after NACT greater than 80% was an independent preoperative predictive factor for complete cytoreduction (P = 0.002). Progressive disease on follow-up image during NACT was an independent preoperative predictive factor for early recurrence and death (P Conclusions A significant drop of CA-125 after NACT and progressive disease on follow-up image are independent preoperative predictors for complete cytoreduction and early recurrence and death.

Objectives. Terlipressin is safely used for acute variceal bleeding. However, side effects, such as hyponatremia, although very rare, can occur. We investigated the development of hyponatremia in cirrhotic patients who had acute variceal bleeding treated with terlipressin and the identification of the risk factors associated with the development of hyponatremia. Design and Methods. This retrospective, case-control study investigated 88 cirrhotic patients who developed hyponatremia and 176 controls that did not develop hyponatremia and were matched in terms of age and gender during the same period following terlipressin administration. Results. The overall change in serum sodium concentration and the mean lowest serum sodium concentration were 3.44 ± 9.55 and 132.44 ± 8.78 mEq/L during treatment, respectively. Multivariate analysis revealed that baseline serum sodium was an independent positive predictor, and the presence of baseline serum creatinine, HBV, DM, creatinine, and shock on admission was independent negative predictors of hyponatremia (P<0.05). Conclusion. The presence of HBV, DM, the baseline serum sodium, shock on admission, and especially baseline creatinine may be predictive of the development of hyponatremia after terlipressin treatment. Therefore, physicians conduct vigilant monitoring associated with severe hyponatremia when cirrhotic patients with preserved renal function are treated with terlipressin for variceal bleeding.

BACKGROUND Previously proposed criteria for preoperatively identifying endometrial cancer patients at low risk for lymph node metastasis remain to be verified. For this purpose, a prospective, multicenter observational study was performed. METHODS Eligible patients with histologically confirmed endometrial cancer underwent magnetic resonance imaging (MRI) and serum cancer antigen 125 (CA 125) testing before surgery. The following criteria were used to identify low-risk patients: 1) endometrioid-type cancer, 2) no evidence of deep myometrial invasion on MRI, 3) no enlarged lymph nodes on MRI, 4) no suspicious metastasis out of the uterine corpus, and 5) serum CA 125 levels less than 35 U/mL. Systematic pelvic and/or para-aortic lymphadenectomy was performed for all patients. The primary endpoint was estimation of the negative predictive value (NPV). RESULTS From January 2012 to December 2014, 529 patients from 20 hospitals in 3 Asian countries were consecutively enrolled. According to our criteria, 272 patients (51.4%) were categorized into the low-risk group. Fifty-three of the 529 patients (10.0%) had lymph node metastases; these patients included 8 (2.9%) falsely categorized as low-risk. The sensitivity and specificity of the criteria were 84.9% and 55.5%, respectively. The NPV of 97.1% was higher than the predefined target endpoint of 96%. CONCLUSIONS The low-risk criteria based on preoperative tests were confirmed to be reliable and accurate for identifying patients at low risk for lymph node metastasis. These criteria may facilitate patient counseling and surgical decision making. Cancer 2017;123:263–272. © 2016 American Cancer Society.

Objectives Although vertebroplasty is very effective for relieving acute pain from an osteoporotic vertebral compression fracture, not all patients who undergo vertebroplasty receive the same degree of benefit from the procedure. In order to identify the ideal candidate for vertebroplasty, pre-operative prognostic demographic or clinico-radiological factors need to be identified. The objective of this study was to identify the pre-operative prognostic factors related to the effect of vertebroplasty on acute pain control using a cohort of surgically and non-surgically managed patients. Patients and Methods Patients with single-level acute osteoporotic vertebral compression fracture at thoracolumbar junction (T10 to L2) were followed. If the patients were not satisfied with acute pain reduction after a three-week conservative treatment, vertebroplasty was recommended. Pain assessment was carried out at the time of diagnosis, as well as three, four, six, and 12 weeks after the diagnosis. The effect of vertebroplasty, compared with conservative treatment, on back pain (visual analogue score, VAS) was analysed with the use of analysis-of-covariance models that adjusted for pre-operative VAS scores. Results A total of 342 patients finished the 12-week follow-up, and 120 patients underwent vertebroplasty (35.1%). The effect of vertebroplasty over conservative treatment was significant regardless of age, body mass index, medical comorbidity, previous fracture, pain duration, bone mineral density, degree of vertebral body compression, and canal encroachment. However, the effect of vertebroplasty was not significant at all time points in patients with increased sagittal vertical axis. Conclusions For single-level acute osteoporotic vertebral compression fractures, the effect of vertebroplasty was less favourable in patients with increased sagittal vertical axis (> 5 cm) possible due to aggravation of kyphotic stress from walking imbalance. Cite this article: Y-C. Kim, D. H. Bok, H-G. Chang, S. W. Kim, M. S. Park, J. K. Oh, J. Kim, T-H. Kim. Increased sagittal vertical axis is associated with less effective control of acute pain following vertebroplasty. Bone Joint Res 2016;5:544–551. DOI: 10.1302/2046-3758.511.BJR-2016-0135.R1.

This study investigated depot-specific mRNA expression of uncoupling protein 1 (UCP1) in human white adipose tissue (WAT) and its association with obesity-related markers. We recruited 39 normal-weight, 41 nondiabetic obese, and 22 diabetic obese women. We measured UCP1 mRNA expression in abdominal visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT), and investigated the associations between UCP1 mRNA expression in VAT and SAT, and obesity-related markers including mRNA expression of leptin, adiponectin, CCAAT-enhancer-binding protein homologous protein (CHOP), and positive regulatory domain-containing protein 16 (PRDM16). We also evaluated UCP1 mRNA expression in differentiated human white adipocytes after treatment with various stressors and metabolic improvement agents in vitro. UCP1 mRNA in VAT was significantly higher than in SAT in all groups. UCP1 mRNA in SAT was negatively correlated with BMI, total abdominal fat area, visceral fat area, blood pressure, fasting glucose, insulin, HOMA-IR score, triglyceride, hsCRP, fasting leptin levels, and adipocyte size. UCP1 mRNA in SAT was positively correlated with fasting adiponectin levels. UCP1 mRNA in VAT was negatively correlated with visceral-to-subcutaneous fat ratio (VSR), fasting glucose, and triglyceride levels. In SAT, UCP1 mRNA was negatively correlated with mRNA expression of leptin and CHOP, and positively correlated with mRNA expression of adiponectin. The expression of PRDM16 was positively correlated with UCP1 mRNA in both VAT and SAT. UCP1 mRNA expression in differentiated human white adipocytes was significantly reduced after incubation with thapsigargin, tunicamycin, homocysteine, TNF-α, or IL-β, and significantly increased after incubation with exendin 4, dapagliflozin, and telmisartan. This study demonstrated depot-specific mRNA expression of UCP1 and its association with obesity-related markers in human WAT. UCP1 mRNA in human white adipocytes was suppressed by inflammatory agents and enhanced by metabolic improvement agents. UCP1 in human WAT might participate in the pathogenesis of obesity-related metabolic diseases.

Aims The aim of this study was to evaluate the outcome of spinal instrumentation in haemodialyzed patients with native pyogenic spondylodiscitis. Spinal instrumentation in these patients can be dangerous due to rates of complications and mortality, and biofilm formation on the instrumentation. Patients and Methods A total of 134 haemodialyzed patients aged more than 50 years who underwent surgical treatment for pyogenic spondylodiscitis were included in the study. Their mean age was 66.4 years (50 to 83); 66 were male (49.3%) and 68 were female (50.7%). They were divided into two groups according to whether spinal instrumentation was used or not. Propensity score matching was used to attenuate the potential selection bias. The outcome of treatment was compared between these two groups. Results A total of 89 patients (66.4%) underwent non-instrumented surgery and 45 (33.5%) underwent instrumented surgery. There were no significant differences in the rates of postoperative complications, except for an increased rate of wound problems in the instrumented group, which was found in the unmatched cohorts (p = 0.034). There were no significant differences in the rate of recurrent infections (p = 0.328 for the unmatched cohort; p = 0.269 for the matched cohort) and mortality rate, including in-hospital (p = 0.713 for the unmatched cohort; p = 0.738 for the matched cohort) and one-year rates (p = 0.363 for the unmatched cohort; p = 0.787 for the matched cohort), between the groups. However, the interval between the initial diagnosis and the first recurrence was significantly longer in the instrumented group (p = 0.008 for the unmatched cohort; p = 0.032 for the matched cohort). Conclusion Instrumented surgery for haemodialyzed patients with pyogenic spondylodiscitis showed similar outcomes, including recurrence and mortality, to non-instrumented surgery, despite the instrumented group having more severe neurological deficit, a larger number of involved levels, and increased kyphotic angle.

A simple method for fabricating a liquid metal (LM) pattern on a polydimethylsiloxane substrate through the process of contact printing is introduced in this paper. This material is easily oxidized when it is exposed to air; consequently, it is difficult to manipulate. Contact printing is a fabrication process based on an adhesive force between interfaces. Adhesion is enhanced by forming a new oxide layer; thus, the LM film on a flat mold is transferred to another mold by contact printing. Electrical conductivity of the transferred LM is 1.93 × 106 S/m, which is sufficiently high for its usage as an electrode in electric circuits. The resolution of the LM pattern can be controlled at ~20 μm and a complex pattern can be fabricated. Furthermore, the LM is semi-transparent and it is visually imperceptible when observed from a distance. Using the semi-transparent LM electrode, a LM triboelectric nanogenerator is fabricated. The device demonstrates normal performance as an energy harvesting system; consequently, the LM patterned by contact printing can be applied to wearable self-powered electronics.

Background Palliative chemotherapy should be used with caution when attempting to alleviate symptoms in patients with end-stage cancer. However, palliative chemotherapy continues to be utilized in cancer patients during their last stages of life. In this study, we analyzed the pattern of chemotherapy administered during the last 6 months of life in patients with end-stage gynecologic cancer who were treated with active palliative chemotherapy for the past 10 years. Method We retrospectively analyzed the data for patients with gynecologic cancer who died after undergoing active palliative chemotherapy without receiving hospice management at Asan Medical Center from 2006 to 2015. Patients were divided into two groups: those who died between 2006 and 2010, and those who died between 2011 and 2015. Based on the electronic medical records, the demographic and baseline characteristics of the patients, hospital admission during the last 6 months, invasive procedures, palliative chemotherapy patterns, and the time of the last chemotherapy session were confirmed. Results A total of 193 patients with gynecologic cancer were eligible for this study. 92 patients died during 2006 to 2010, and 101 patients died during 2011 to 2015. The mean frequency of admission during the last 6 months was 5.12 for those who died in 2006–2010 and 6.06 for those who died during 2011–2015 (p = 0.003); similarly, the mean frequency of palliative chemotherapy during the last 6 months was 3.84 (2006–2010) vs. 4.93 times (2011–2015; p

Angiopoietin-like protein 2 has been proposed to be a key mediator linking obesity and insulin resistance. However, no detailed study of ANGPTL2 expression in human adipose tissues has yet been reported. To investigate the pattern and regulation of ANGPTL2 expression in human adipose tissues in obesity and its related diseases, we recruited 32 non-diabetic and 13 type 2 diabetic obese women and 32 normal-weight women. ANGPTL2 mRNA was expressed at a similar level in visceral and subcutaneous adipose tissues. Adipose tissue ANGPTL2 mRNA was much higher in obese patients. Adipose tissue ANGPTL2 mRNA and serum ANGPTL2 levels showed strong associations with metabolic parameters associated with insulin resistance. In adipose tissue, ANGPTL2 mRNA was closely correlated with the expression of genes involved in inflammation and ER stress. ANGPTL2 mRNA was principally expressed in adipocytes, and its expression was markedly higher in the adipocyte but non-adipocyte fraction of obese adipose tissues. Culture of human adipocytes under conditions mimicking the microenvironment of obese adipose tissue (especially, increased ER stress) stimulated ANGPTL2 gene expression and secretion. In addition, co-culture of adipocytes and macrophages suggested that ANGPTL2 excessively produced by adipocytes, may contribute inflammation and remodeling in obese adipose tissues, thereby promoting insulin resistance.

Objectives To evaluate the outcome of fertility-sparing surgery among young women with early-stage clear cell carcinoma of the ovary. Methods In a retrospective study, data were reviewed for patients aged 45 years or younger who had FIGO stage I clear cell carcinoma of the ovary and had attended one institution in South Korea between December 1999 and December 2009. Outcomes were compared between women undergoing fertility-sparing surgery, defined as preservation of the uterus and at least one adnexa, and those undergoing radical surgery. Results Overall, 47 patients were included (22 underwent fertility-sparing surgery, 25 radical surgery). After a median follow-up of 72 months (range 8–175), 5 (23%) patients who underwent fertility-sparing surgery and 5 (20%) in the radical surgery group had recurrent disease ( P = 0.820). The mean time to recurrence was 19 months after fertility-sparing surgery versus 20 months after radical surgery ( P = 0.935). The anatomical location of recurrence did not differ. There was no difference in 5-year disease-free survival (77% vs 84%; P = 0.849) or 5-year overall survival (91% vs 88%; P = 0.480). Conclusion Fertility-sparing surgery was found to be a safe alternative for young women with FIGO stage I clear cell carcinoma of the ovary who wish to preserve fertility.

The role of disseminated intravascular coagulation (DIC) has not been extensively studied in patients with sepsis. A prospective study was performed in a single university hospital. The incidences of DIC at day 1 (

Postoperative fluid collection is a major complication after pancreaticoduodenectomy and can lead to increased mortality and hospital length of stay. External drainage has widely been used for postoperative fluid collections. Recently, EUS-guided drainage has also been used successfully in treating postoperative fluid collections. A 60-year-old woman was admitted due to weight loss and jaundice. She underwent pancreaticoduodenectomy for cholangiocarcinoma of the common bile duct. After 2 weeks, she had fever with abdominal pain and leukocytosis. CT showed a increased fluid collection in superior recess of lesser sac and EUS-guided drainage was performed. The symptoms resolved without any complication after drainage. This is the first case report of EUS-guided drainage for lesser sac in Korea. Korean J Pancreatobiliary 2015;20(4):228-233

Objective: To compare the intraoperative and postoperative outcomes of laparoendoscopic single-site surgery (LESS) versus conventional laparoscopic surgery in women with ovarian mature cystic teratoma. Methods: A retrospective review of 303 women who underwent LESS (n=139) or conventional laparoscopic surgery (n=164) due to ovarian mature cystic teratoma was performed. Intra- and postoperative outcomes were compared between the two groups. Results: There was no intergroup difference in age, body weight, height, body mass index, comorbidities, tumor size, bilaterality of tumor, or the type of surgery. However, more patients in the LESS group had a history of previous abdominal surgery (19.4% vs. 6.7%, P=0.001). Surgical outcomes including operating time (89 vs. 87.8 minutes, P=0.734), estimated blood loss (69.4 vs. 68.4 mL, P=0.842), transfusion requirement (2.2% vs. 0.6%, P=0.336), perioperative hemoglobin level change (1.3 vs. 1.2 g/dL, P=0.593), postoperative hospital stay (2.0 vs. 2.1 days, P=0.119), and complication rate (1.4% vs. 1.8%, P=0.999) did not differ between LESS and conventional groups. Postoperative pain scores measured using a visual analogue scale were significantly lower in the LESS group at 8 hours (P=0.021), 16 hours (P=0.034), and 32 hours (P=0.004) after surgery, and 32 of 139 patients (23%) in the LESS group and 78 of 164 patients (47.6%) in the conventional group required at least one additional analgesic (P

Objective To analyze the oncologic and reproductive outcomes of pediatric and young adolescents with malignant ovarian germ cell tumors (MOGCTs). Methods Pediatric or young adolescent girls aged 16years or under with MOGCT were eligible for this study. Results Forty-two pediatric or adolescent girls with MOGCT met the inclusion criteria. The median age was 12years (range, 6–16years) and 29 patients were premenarchal. The most common histologic type was immature teratoma, and 30 patients (54.3%) had stage I MOGCT. All patients underwent fertility-sparing surgery, which was defined as the preservation of at least one adnexa and the uterus. No patient had residual disease after surgery. Thirteen patients had tumor spillage, two patients had a positive peritoneal cytology, and two patients had lymph node metastasis. After surgery, 31 patients received adjuvant chemotherapy with bleomyocin, etoposide, and cisplatin (BEP) (median, 4cycles; range, 1–6 cycles). After a median follow-up time of 93months (range, 22–217 months), six patients had a recurrence of the disease, and one patient died. The 5-year disease-free and overall survival rates were 85% and 97%, respectively. Among the surviving 41 patients, seven were premenarchal, 30 had regular menstruation, and three had irregular menstruation. No patient had premature ovarian failure. Conclusion All patients received uniform treatment consisting of fertility-sparing complete cytoreductive surgery followed by BEP chemotherapy. Regardless of histologic type and FIGO stage, the oncologic outcomes were excellent and the reproductive outcomes were favorable.

자가면역췌장염은 자가면역 기전에 의해 유발되는 특이한 만성췌장염의 한 형태로서 영상검사, 실험실 검사, 조직 및 임상 소견에서 특징적인 양상을 보인다. 자가면역췌장염의 주된 치료는 스테로이드 및 면역억제제인 반면, 췌장암의 주 된 치료는 수술적 절제이며 두 질환의 예후 또한 매우 다르 므로, 임상에서 자가면역췌장염과 췌장암의 감별 진단은 매 우 중요하다. 임상증상과 영상검사만으로는 감별이 어려운 경우가 있는데, 혈청 면역글로불린 G4 (immunoglobulin G4, IgG4) 수치는 자가면역췌장염의 진단에 많은 도움이 되 는 것으로 알려져 있다. 최신의 자가면역췌장염의 국제진 단기준에 따르면 혈청 IgG4가 정상 상한보다 증가되어 있으 면 레벨 2 증거가 되며, 정상 상한보다 2배 이상 증가되어 있 으면 레벨 1 증거라고 하여서, 정상 상한보다 2배 이상 증가 한 경우는 자가면역췌장염에 매우 특이한 소견이라고 규정 하였다. 일부의 췌장암 환자에서 혈청 IgG4가 증가하였다 는 보고가 있는데, 해외의 문헌보고에서는 췌장암 환자에서 혈청 IgG4가 정상 상한의 4배 이상 상승된 경우가 있었지 만, 아직 국내에서는 보고된 바가 없다. 최근 저자들은 혈 A Case of Pancreatic Cancer with Markedly Elevated Serum Immunoglobulin G4

Objective Malignant Brenner tumors (MBTs) of the ovary are very rare, and their definition, biology, and treatment modality have not been established. This study investigated the clinical characteristics of MBTs and the importance of chemotherapy for recurrent disease. Materials and methods We conducted a retrospective analysis of 10 patients with MBT of the ovary treated at a single tertiary center from 1991 to 2013. Results The median age was 55.5 years (range, 37–68 years). Nine of the 10 patients were symptomatic. The median size of the ovarian tumors was 10.5 cm (range, 2.5–25.0 cm). The cancer antigen-125 level was elevated in three patients. Six patients had a stage I tumor, one had a stage II tumor, two had a stage III tumor, and one had a stage IV tumor. Six patients received systemic adjuvant chemotherapy after surgery. The mean follow-up duration was 54.5 months (range, 8–173 months). Disease recurrence occurred in four of the 10 patients. The median time to recurrence was 11 months (range, 9–18 months). Two patients with locoregional recurrence showed favorable results after chemotherapy, regardless of the initial stage of the tumor. The patient with the stage IIIC tumor is alive at 13 months after recurrence on current chemotherapy. The patient with the stage IV tumor showed no evidence of the disease > 12 years after the last chemotherapy. Lastly, two patients with distant recurrence died after showing a long-term survival of 49 months and 88 months, respectively, after recurrence and intensive chemotherapy. Conclusion Our results showed that systemic chemotherapy is beneficial in patients with recurrence of a primary MBT of the ovary, especially in the locoregional recurrence.

We used a 3-dimensional (3D) printer to create anatomical replicas of real lesions and tested its application in cervical cancer. Our study patient decided to undergo radical hysterectomy after seeing her 3D model which was then used to plan and simulate this surgery. Using 3D printers to create patient-specific 3D tumor models may aid cervical cancer patients make treatment decisions. This technology will lead to better surgical and oncological outcomes for cervical cancer patients. J. Surg. Oncol. 2016;114:150-152. © 2016 Wiley Periodicals, Inc.

Background Lymph node metastasis is a significant predictive factor for disease recurrence and survival in cervical cancer patients. Given the importance of lymph node metastasis, it is imperative that patients harboring metastasis are identified and can undergo appropriate treatment. Sentinel lymph node (SLN) mapping has drawn attention as a lymph node mapping technique. We evaluated the feasibility and efficacy of (SLN) mapping using indocyanine green (ICG) in cervical cancer. Methods We performed a single-center, retrospective study of 103 surgically treated cervical cancer patients who underwent SLN mapping. After using ICG to detect SLN during surgery, we removed the SLNs followed by laparoscopic or robotic-assisted radical surgery and bilateral pelvic lymphadenectomy. Results Stage IB1 was the most common (61.17%). At least one SLN was detected in all cases. Eighty-eight patients (85.44%) had bilateral pelvic SLNs. The mean number of SLN per patient was 2.34. The side-specific sensitivity was 71.43%, the specificity was 100%, the negative predictive value (NPV) was 93.98%, and the false negative rate (FNR) was 28.57%. In cases of tumors smaller than 2 cm with negative lymph node metastasis on imaging, the study revealed a side-specific sensitivity of 100%, a specificity of 100%, a NPV of 100%, and a FNR of 0%. Large tumor size (≥ 4 cm), a previous history of a loop electrosurgical excision procedure (LEEP), depth of invasion (≥ 50%), the microscopic parametrial (PM) invasion, and vaginal extension were significantly associated with the false-negative detection of SLN. Moreover, the microscopic PM invasion was the only risk factor of the false-negative detection of SLN in multivariate analysis. Conclusion SLN mapping with ICG in cervical cancer is feasible and has high detection rate. The sensitivity of 100% was high enough to perform SLN biopsy alone in an early stage in which the tumor is less than 2 cm, with no lymphadenopathy on image examination. However, for large or invasive tumors, we would have to be cautious about performing SLN biopsy alone. Trial registration Retrospectively registered 2017-0600.