Prognostic Value of Postoperative CEA Clearance in Rectal Cancer Patients with High Preoperative CEA Levels

PURPOSE: We determined the prognostic value of carcinoembryonic antigen (CEA) clearance after tumor resection with serial evaluation of postoperative CEA levels in rectal cancer. METHODS: Between 1994 and 2004, we retrospectively reviewed 122 patients with rectal cancer whose serum CEA levels were measured on the preoperative day and postoperative days 7 and 30. Patients with preoperative CEA levels <5.0 ng/ml were excluded. An exponential trend line was drawn using the three CEA values. Patients were categorized into three groups based on R(2) values calculated through trend line, which indicates the correlation coefficient between exponential graph and measured CEA values: exponential decrease group (group 1: 0.9 < R(2) < or = 1.0), nearly exponential decrease group (group 2: 0.5 < R(2) < or = 0.9), and randomized clearance group (group 3: 0.5 < or = R(2)). We then analyzed the CEA clearance pattern as a prognostic indicator. RESULTS: With a median follow-up of 57 months, the 5-year overall survival was 62.3% vs. 48.1% vs. 25% and the 5-year disease-free survival was 58.6% vs. 52.7% vs. 25% among groups 1, 2, and 3 (P = 0.014, P = 0.027, respectively) in patients with stage III rectal cancer. For those with stage II rectal cancer, the 5-year overall survival rate of group 1 was significantly better than groups 2 and 3 (88.8% vs. 74.1%, respectively, P = 0.021). CONCLUSIONS: the postoperative pattern of CEA clearance is a useful prognostic determinant in patients with rectal cancer. Patients with a randomized pattern of CEA clearance after tumor resection should be regarded as having the possibility of a persistent CEA source and may require consideration of intensive follow-up or adjuvant therapy.ope

Decreased health-related quality of life in disease-free survivors of differentiated thyroid cancer in Korea

<p>Abstract</p> <p>Background</p> <p>Concern regarding the health-related quality of life (HRQOL) of long-term survivors of thyroid cancer has risen due to the rapid increase in the incidence of thyroid cancer, which generally has an excellent prognosis. The aim of this study was to evaluate the status of HRQOL in disease-free survivors of differentiated thyroid carcinoma (DTC) and to evaluate the important determinants of HRQOL.</p> <p>Methods</p> <p>This was a cross-sectional study in which we interviewed consecutive disease-free survivors of DTC. Three different validated questionnaires ("EORTC QLQ-C30" for various functional domains, the "brief fatigue inventory (BFI)" and the "hospital anxiety and depression scale" (HADS)) were used. Data from a large, population based survey of 1,000 people were used as a control.</p> <p>Results</p> <p>The response rate for the questionnaires was 78.9% (316/401). Disease-free survivors of DTC showed a decreased HRQOL in all five functional domains (physical, role, cognitive, emotional, and social) on the EORTC QLQ-C30 compared with controls (<it>P </it>< 0.01). BFI and HADS-anxiety scores also showed greater distress in disease-free survivors of DTC than in controls (<it>P </it>< 0.05). A multiple regression analysis for the determinants of HRQOL showed that the HADS-anxiety, HADS-depression, and BFI scores were the most significant components of decreased HRQOL.</p> <p>Conclusions</p> <p>Although disease-free survivors of DTC are expected to have disease-specific survival comparable to the general population, they experience a significantly decreased HRQOL. Anxiety, depression, and fatigue were the major determinants of the decreased HRQOL. Supportive psychological care should be integrated into the management of long-term survivors of DTC.</p

Korean Type 2 Diabetes Patients have Multiple Adenomatous Polyps Compared to Non-diabetic Controls

We tested the correlation between diabetes and aggressiveness of colorectal polyps in diabetic patients and matched non-diabetic controls. We retrospectively studied 3,505 type 2 diabetes (T2DM) patients without gastrointestinal symptoms who underwent colonoscopy for colorectal cancer at Samsung Medical Center, Seoul, Korea from August 1995 to August 2009. We matched 495 non-diabetic subjects with colon polyps to the diabetic patients in whom polyps were detected by year of colonoscopy, age, sex and body mass index (BMI). Among the 3,505 T2DM patients screened, 509 were found to have 1,136 colon polyps. Those with diabetes had a greater proportion of adenomatous polyps (62.8% vs 53.6%) compared to the control. Multivariate logistic regression analysis identified DM, male gender, age and BMI as independent risk factors for multiple polyps (more than three polyps). Polyp multiplicity in diabetic patients was significantly associated with male gender (OR 2.360, P = 0.005), age (OR 1.033, P = 0.005) and BMI (OR 1.077, P = 0.028). Neither aspirin nor metformin use affected either size or number of polyps in diabetic patients. Male patients older than 65 yr with T2DM and BMI greater than 25 have increased risk for multiple adenomatous polyps and should be screened with colonoscopy to prevent colorectal cancer

Autophagy deficiency leads to protection from obesity and insulin resistance by inducing Fgf21 as a mitokine

Despite growing interest and a recent surge in papers, the role of autophagy in glucose and lipid metabolism is unclear. We produced mice with skeletal muscle–specific deletion of Atg7 (encoding autophagy-related 7). Unexpectedly, these mice showed decreased fat mass and were protected from diet-induced obesity and insulin resistance; this phenotype was accompanied by increased fatty acid oxidation and browning of white adipose tissue (WAT) owing to induction of fibroblast growth factor 21 (Fgf21). Mitochondrial dysfunction induced by autophagy deficiency increased Fgf21 expression through induction of Atf4, a master regulator of the integrated stress response. Mitochondrial respiratory chain inhibitors also induced Fgf21 in an Atf4-dependent manner. We also observed induction of Fgf21, resistance to diet-induced obesity and amelioration of insulin resistance in mice with autophagy deficiency in the liver, another insulin target tissue. These findings suggest that autophagy deficiency and subsequent mitochondrial dysfunction promote Fgf21 expression, a hormone we consequently term a 'mitokine', and together these processes promote protection from diet-induced obesity and insulin resistance

Long-acting FC-fusion rhGH (GX-H9) shows potential for up to twice-monthly administration in GH-deficient adults

Hybrid Fc-fused rhGH (GX-H9) is a long-acting recombinant human growth hormone (GH) under clinical development for both adults and children with GH deficiency (GHD). We compared the safety, pharmacokinetics and pharmacodynamics of weekly and every other week (EOW) dosages of GX-H9 with those of daily GH administration in adult GHD (AGHD) patients.This was a randomized, open-label, active-controlled and dose-escalation study conducted in 16 endocrinology centers in Europe and Korea.Forty-five AGHD patients with or without prior GH treatment were enrolled. Patients with prior GH treatments were required to have received the last GH administration at least 1 month prior to randomization. Subjects were sequentially assigned to treatment groups. Fifteen subjects were enrolled to each treatment group and randomly assigned to receive either GX-H9 or Genotropin (4:1 ratio). GX-H9 dosage regimens for Groups 1, 2 and 3 were 0.1 mg/kg weekly, 0.3 mg/kg EOW and 0.2 mg/kg EOW, respectively. All Genotropin-assigned subjects received 6 µg/kg Genotropin, regardless of treatment group. Main outcome analyses included measurements of serum insulin-like growth factor 1 (IGF-I), safety, pharmacokinetics, pharmacodynamics and immunogenicity.Mean GX-H9 peak and total exposure increased with an increase in dose after a single-dose administration. The mean IGF-I response was sustained above baseline over the intended dose interval of 168 h for the weekly and 336 h for the EOW GX-H9 groups. Safety profiles and immunogenicity were not different across the treatment groups and with Genotropin.GX-H9 has the potential for up to twice-monthly administration

Depression, antidepressant use, and the risk of type 2 diabetes: a nationally representative cohort study

BackgroundPrevious studies have reported that depression can increase the risk of type 2 diabetes. However, they did not sufficiently consider antidepressants or comorbidity.MethodsThe National Health Insurance Sharing Service database was used. Among the sample population, 276,048 subjects who had been diagnosed with depression and prescribed antidepressants (DEP with antidepressants group) and 79,119 subjects who had been diagnosed with depression but not prescribed antidepressants (DEP without antidepressants group) were found to be eligible for this study. Healthy controls (HCs) were 1:1 matched with the DEP with antidepressants group for age and sex. We followed up with them for the occurrence of type 2 diabetes.ResultsIn the group of DEP with antidepressants, although the risk of type 2 diabetes increased compared to HCs in a crude analysis, it decreased when comorbidity was adjusted for. In the group of DEP without antidepressants, the risk of type 2 diabetes decreased both in the crude model and the adjusted models. The risk varied by age group and classes or ingredients of antidepressants, with young adult patients showing an increased risk even in the fully adjusted model.ConclusionOverall, those with depression had a reduced risk of type 2 diabetes. However, the risk varied according to the age at onset, comorbidity, and type of antidepressants

Primary leiomyosarcoma of the pancreas

Primary sarcomas of the pancreas are extremely rare, accounting for 0.1% of malignant pancreatic (non-islet) neoplasms. Pancreatic leiomyosarcoma is a highly aggressive malignancy that spreads in a similar manner to gastric leiomyosarcoma, i.e., by adjacent organ invasion, hematogenous spread, and lymph node metastasis. These tumors are large at the time of diagnosis and are usually found at an advanced stage. We report a case of a 70-year-old female with intermittent right upper quadrant abdominal discomfort. Radiological, histopathological, and immunohistochemical studies revealed the tumor to be a primary leiomyosarcoma of the pancreas. Herein, we describe a patient with a primary leiomyosarcoma of the pancreas who presented with clinical and radiological findings indicative of a mass in the pancreatic head

The Ability of β-Cells to Compensate for Insulin Resistance is Restored with a Reduction in Excess Growth Hormone in Korean Acromegalic Patients

The aim of this study was to assess the prevalence of diabetes and to study the effects of excess growth hormone (GH) on insulin sensitivity and β-cell function in Korean acromegalic patients. One hundred and eighty-four acromegalic patients were analyzed to assess the prevalence of diabetes, and 52 naïve acromegalic patients were enrolled in order to analyze insulin sensitivity and insulin secretion. Patients underwent a 75 g oral glucose tolerance test with measurements of GH, glucose, insulin, and C-peptide levels. The insulin sensitivity index and β-cell function index were calculated and compared according to glucose status. Changes in the insulin sensitivity index and β-cell function index were evaluated one to two months after surgery. Of the 184 patients, 17.4% were in the normal glucose tolerance (NGT) group, 45.1% were in the pre-diabetic group and 37.5% were in the diabetic group. The insulin sensitivity index (ISI0,120) was significantly higher and the HOMA-IR was lower in the NGT compared to the diabetic group (P = 0.001 and P = 0.037, respectively). The ISI0,120 and disposition index were significantly improved after tumor resection. Our findings suggest that both insulin sensitivity and β-cell function are improved by tumor resection in acromegalic patients