Germline PRKACA amplification-associated primary pigmented nodular adrenocortical disease: a case report and literature review

SUMMARY Primary pigmented nodular adrenocortical disease (PPNAD) is a rare adrenocorticotropin hormone (ACTH)-independent Cushing's syndrome (CS). Pediatric patients with PPNAD typically have unusual skin lesions and slow growth with unknown causes. We present a case of a female Chinese patient with PPNAD caused by the germline PRKACA gene copy number gain of chromosome 19. The patient initially presented with kidney stones, short stature, and obesity. After further testing, it was discovered that the patient had diabetes, mild hypertension, low bone mass, a low ACTH level, and hypercortisolemia, and neither the low-dose or high-dose dexamethasone suppression test was able to inhibit hematuric cortisol, which paradoxically increased. PPNAD was pathologically diagnosed after unilateral adrenalectomy. Chromosome microarrays and whole exon sequencing analyses of the peripheral blood, as well as testing of sectioned adrenal tissue, showed a rise in the copy number of the duplication-containing PRKACA gene on chromosome 19p13.13p13.12, a de novo but not heritable gene defect that causes disease. The clinical signs and symptoms supported the diagnosis of Carney complex (CNC). One significant mechanism of CNC pathogenesis may be the rise in germline PRKACA copy number of chromosome 19. When assessing PPNAD patients for CNC, the possibility of PRKACA gene amplification should be considered. The effect of PRKACA gene amplification on the clinical manifestations of CNC needs to be confirmed by more cases.

Germline PRKACA amplification-associated primary pigmented nodular adrenocortical disease: a case report and literature review.

Primary pigmented nodular adrenocortical disease (PPNAD) is a rare adrenocorticotropin hormone (ACTH)-independent Cushing's syndrome (CS). Pediatric patients with PPNAD typically have unusual skin lesions and slow growth with unknown causes. We present a case of a female Chinese patient with PPNAD caused by the germline PRKACA gene copy number gain of chromosome 19. The patient initially presented with kidney stones, short stature, and obesity. After further testing, it was discovered that the patient had diabetes, mild hypertension, low bone mass, a low ACTH level, and hypercortisolemia, and neither the low-dose or high-dose dexamethasone suppression test was able to inhibit hematuric cortisol, which paradoxically increased. PPNAD was pathologically diagnosed after unilateral adrenalectomy. Chromosome microarrays and whole exon sequencing analyses of the peripheral blood, as well as testing of sectioned adrenal tissue, showed a rise in the copy number of the duplication-containing PRKACA gene on chromosome 19p13.13p13.12, a de novo but not heritable gene defect that causes disease. The clinical signs and symptoms supported the diagnosis of Carney complex (CNC). One significant mechanism of CNC pathogenesis may be the rise in germline PRKACA copy number of chromosome 19. When assessing PPNAD patients for CNC, the possibility of PRKACA gene amplification should be considered. The effect of PRKACA gene amplification on the clinical manifestations of CNC needs to be confirmed by more cases.

Acute Thyrotoxic Myopathy Combined with Neck Pain: A Case Report.

INTRODUCTION: Acute thyrotoxic myopathy (ATM) is a rare and potentially lethal complication of thyrotoxicosis. The typical clinical symptoms of ATM are characterized by bulbar paralysis. Reports of the successful treatment of ATM are sporadic due to its low incidence. However, no English literature has reported Chinese patients with ATM and neck pain. Here, we report for the first time a Chinese patient with ATM and neck pain who recovered through large doses of systemic glucocorticoids and one intrathyroidal steroid injection. CASE REPORT: A 23-year-old woman visited our hospital with a two-year history of progressive weakness of her bulbar muscles, hoarseness, cough when swallowing, dysphagia, and a one-month history of recurrent painful swelling of the thyroid gland. She was diagnosed with ATM, chronic thyrotoxic myopathy (CTM), and Graves' ophthalmopathy (GO) due to Graves' disease (GD). After she was treated with a combination of low-dose glucocorticoids, antithyroid drugs (ATDs), propranolol, and ultrasound-guided percutaneous intrathyroidal injection of glucocorticoids, her bulbar paralysis, proximal myopathy, and neck pain simultaneously improved without recurrence during follow-up. To our knowledge, this is the first case report of a patient with ATM, CTM, GD, GO and neck pain treated by administering a combination of low-dose glucocorticoids, one intrathyroidal steroid injection and antithyroid agents. CONCLUSIONS: Clinicians should consider ATM and intervene with aggressive glucocorticoid therapy, and this is the key to reversing the progression of ATM when a patient has bulbar paralysis and thyrotoxic symptoms. Our case report references the clinical diagnosis and treatment of such cases.

Ultrasound measurement of vastus lateralis and vastus medialis muscle parameters to identify chronic thyrotoxic myopathy.

Introduction: Chronic thyrotoxic myopathy (CTM) is a common, easily neglected complication of hyperthyroidism. There are currently no standard diagnostic criteria for CTM, and the ultrasonic characteristics of CTM-affected skeletal muscle remain unclear. Herein, we aimed to evaluate hyperthyroid patients for CTM by ultrasound and identify ultrasonic muscle parameter cutoffs for CTM diagnosis. Materials and methods: Each participant underwent ultrasonography. The original (muscle thickness (MT), pennation angle (PA), and cross-sectional area (CSA)) and corrected (MT/height (HT), MT/body mass index (BMI), CSA/HT, and CSA/BMI) parameters of the vastus lateralis and vastus medialis (VM) were evaluated. The diagnostic effectiveness of ultrasound for predicting CTM was determined using receiver operating characteristic (ROC) curve analysis. Our study included 203 participants: 67 CTM patients (18 males, 49 females), 67 non-CTM patients (28 males, 39 females) and 69 healthy controls (20 males, 49 females). Results: The CTM group had lower muscular ultrasonic and anthropometric parameters, higher thyroid hormone and thyroid-stimulating hormone receptor antibody (TRAb) levels, and a longer duration of hyperthyroidism than the non-CTM group (P < 0.05). The VM-PA, VM-CSA, VM-CSA/HT, and VM-CSA/BMI were lower in females than in males (P < 0.05). Free thyroxine (FT4) and TRAb both showed significant negative correlations with VM-MT, VM-MT/HT, VM-CSA, and VM-CSA/HT (P < 0.05). VM-MT/BMI and VM-CSA/HT, respectively, best predicted male and female CTM (AUC = 0.84, 0.85; cutoff ≤ 0.07, < 4.01). Conclusion: Ultrasound measurement of muscular parameters, especially in the VM, is a valid and feasible way of diagnosing and characterizing possible CTM in hyperthyroidism.

LRP6 Bidirectionally Regulates Insulin Sensitivity through Insulin Receptor and S6K Signaling in Rats with CG-IUGR.

OBJECTIVE: Intrauterine growth restriction followed by postnatal catch-up growth (CG-IUGR) increases the risk of insulin resistance-related diseases. Low-density lipoprotein receptor-related protein 6 (LRP6) plays a substantial role in glucose metabolism. However, whether LRP6 is involved in the insulin resistance of CG-IUGR is unclear. This study aimed to explore the role of LRP6 in insulin signaling in response to CG-IUGR. METHODS: The CG-IUGR rat model was established via a maternal gestational nutritional restriction followed by postnatal litter size reduction. The mRNA and protein expression of the components in the insulin pathway, LRP6/ß-catenin and mammalian target of rapamycin (mTOR)/S6 kinase (S6K) signaling, was determined. Liver tissues were immunostained for the expression of LRP6 and ß-catenin. LRP6 was overexpressed or silenced in primary hepatocytes to explore its role in insulin signaling. RESULTS: Compared with the control rats, CG-IUGR rats showed higher homeostasis model assessment for insulin resistance (HOMA-IR) index and fasting insulin level, decreased insulin signaling, reduced mTOR/S6K/ insulin receptor substrate-1 (IRS-1) serine307 activity, and decreased LRP6/ß-catenin in the liver tissue. The knockdown of LRP6 in hepatocytes from appropriate-for-gestational-age (AGA) rats led to reductions in insulin receptor (IR) signaling and mTOR/S6K/IRS-1 serine307 activity. In contrast, LRP6 overexpression in hepatocytes of CG-IUGR rats resulted in elevated IR signaling and mTOR/S6K/IRS-1 serine307 activity. CONCLUSION: LRP6 regulated the insulin signaling in the CG-IUGR rats via two distinct pathways, IR and mTOR-S6K signaling. LRP6 may be a potential therapeutic target for insulin resistance in CG-IUGR individuals.

Inverted U-Shaped Associations between Glycemic Indices and Serum Uric Acid Levels in the General Chinese Population: Findings from the China Cardiometabolic Disease and Cancer Cohort (4C) Study.

OBJECTIVE: The relationship between serum uric acid (SUA) levels and glycemic indices, including plasma glucose (FPG), 2-hour postload glucose (2h-PG), and glycated hemoglobin (HbA1c), remains inconclusive. We aimed to explore the associations between glycemic indices and SUA levels in the general Chinese population. METHODS: The current study was a cross-sectional analysis using the first follow-up survey data from The China Cardiometabolic Disease and Cancer Cohort Study. A total of 105,922 community-dwelling adults aged ≥ 40 years underwent the oral glucose tolerance test and uric acid assessment. The nonlinear relationships between glycemic indices and SUA levels were explored using generalized additive models. RESULTS: A total of 30,941 men and 62,361 women were eligible for the current analysis. Generalized additive models verified the inverted U-shaped association between glycemic indices and SUA levels, but with different inflection points in men and women. The thresholds for FPG, 2h-PG, and HbA1c for men and women were 6.5/8.0 mmol/L, 11.0/14.0 mmol/L, and 6.1/6.5, respectively (SUA levels increased with increasing glycemic indices before the inflection points and then eventually decreased with further increases in the glycemic indices). CONCLUSION: An inverted U-shaped association was observed between major glycemic indices and uric acid levels in both sexes, while the inflection points were reached earlier in men than in women.

Elevated triglycerides rather than other lipid parameters are associated with increased urinary albumin to creatinine ratio in the general population of China: a report from the REACTION study.

BACKGROUND: Dyslipidaemia has always been regarded as the cornerstone of arteriosclerosis and is related to the pathogenesis of renal insufficiency. However, it is unclear which routinely available lipid parameter is related to urinary albumin to creatinine ratio (UACR). The purpose of this study was to examine the lipid abnormalities associated with UACR in the general population in China. METHODS: The present study was nested in an ongoing Risk Evaluation of cAncers in Chinese diabetic Individuals: A lONgitudinal (REACTION) study, which was designed to demonstrate the association of abnormal glucose metabolism with the risk of cancer in the Chinese population. This cross-sectional study included 34, 569 subjects (11, 390 males and 23, 179 females) from 8 different regional community cohorts, with an average age of 57.9 years. The UACR data were divided into the < 25% group, the 25-49% group, the 50-74% group, and the ≥ 75% group according to the quartile division of the centre where the subjects visited. The lipid classes were defined according to the guidelines for the prevention and treatment of dyslipidaemia in Chinese adults. Multiple logistic regression analysis was used to evaluate the association of the lipid parameters and UACR. RESULTS: Multivariable regression analysis revealed that compared with the other lipid parameters, triglycerides (TG) showed an adjusted odds ratio that was significant in model 1-4. This relationship was attenuated after adjusting for Haemoglobin A1c (HbA1c) and blood pressure (BP), but TG ≥ 2.3 mmol/L was still significantly associated with UACR in total subjects and in both men and women (OR: 1.131, 95% CI 1.065-1.203, P < 0.001 in total subjects; OR: 1.134, 95% CI 1.022-1.258, P = 0.017 in men; OR: 1.129, 95% CI 1.046-1.219, P = 0.002 in women). In the stratified analysis, elevated TG was significantly associated with increased urinary albumin in subjects with eGFR ≥ 90 mL/min per 1.73 m2, 5.6 ≤ FBG < 7.0 or 7.8 ≤ PBG < 11.1 mmol/L, 24 ≤ BMI < 28 kg/m2, 120 ≤ SBP < 140 and/or 80 ≤ DBP < 90 mmHg. CONCLUSIONS: We conclude that high TG levels rather than total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, or non-high-density lipoprotein cholesterol levels are associated with UACR in the general population in China.

Is it sufficient to evaluate bone marrow involvement in newly diagnosed lymphomas using 18F-FDG PET/CT and/or routine iliac crest biopsy? A new approach of PET/CT-guided targeted bone marrow biopsy.

BACKGROUND: To investigate whether PET/CT-guided bone marrow biopsy adds complementary information for evaluation of bone marrow involvement (BMI) in newly diagnosed lymphomas. METHODS: Patients with newly diagnosed lymphomas that received both 18F-FDG PET/CT and bone marrow biopsy (BMB) were included in this retrospective study. PET/CT classification of bone lesions was classified as isolated, multifocal (2 lesions or more), diffuse (homogeneous uptake of the entire axial skeleton), or negative. BMBs included PET/CT-guided targeted BMB and/or the routine unilateral iliac crest biopsy. Of 34 patients with focal lesions on PET/CT scan, 30 received both PET/CT-guided targeted BMB and iliac crest biopsy, and 4 patients received targeted biopsy without iliac crest biopsy. The final diagnosis of BMI depends on BMB results. RESULTS: A total of 299 patients with lymphomas were included. PET/CT classification of bone lesions was isolated (16/5.4%), multifocal (67/22.4%), diffuse (52/17.4%), and negative (164/54.8%). If only positive iliac crest biopsy was considered as the reference standard, the sensitivity of 18F-FDG PET/CT for identifying focal and diffuse BMI was 48 and 56%, respectively, and the respective specificities were 70 and 83%. Three of 30 patients (10.0%) with focal lesions on PET/CT were confirmed to be false-positive by targeted BMB, and 25 of 30 patients (83.3%) with focal lesions on PET/CT were confirmed as false-negative by iliac crest biopsy. CONCLUSION: It is insufficient to evaluate BMI in newly diagnosed lymphomas using both 18F-FDG PET/CT and routine iliac crest biopsy. 18F-FDG PET/CT imaging should be performed before BMB. In focal bone lesions, PET/CT-guided targeted BMB may complement the results of possible false-positive PET/CT and false-negative iliac crest biopsy findings. However, in diffuse and negative lesions, iliac crest biopsy cannot be safely omitted.

PET/CT-guided percutaneous biopsy of FDG-avid metastatic bone lesions in patients with advanced lung cancer: a safe and effective technique.

PURPOSE: 18F-FDG PET/CT should be performed before a diagnostic biopsy site is chosen in patients with a high clinical suspicion of aggressive, advanced tumour. The aim of this study was to evaluate the safety and efficacy of 18F-FDG PET/CT in guiding biopsy of bone metastases in patients with advanced lung cancer. METHODS: PET/CT-guided percutaneous core biopsies were performed in 51 consecutive patients with suspected lung cancer and 18F-FDG-avid bone lesions after whole-body 18F-FDG PET/CT scans. Generally, one tissue sample was obtained from each patient. The final diagnoses were established on the basis of the histology results. The histopathological and molecular testing results were systematically evaluated. RESULTS: A total of 53 samples were obtained for histological examination or molecular testing as a second biopsy was required in two patients in whom the pathological diagnosis was unclear following the first biopsy. The pathological diagnosis and lung cancer classification were confirmed in 48 patients. The epidermal growth factor receptor mutation status was determined in 23 biopsies, and the mutation rate was 30.4 % (7/23). The anaplastic lymphoma kinase mutation status was determined in 19 biopsies, and the mutation rate was 31.6 % (6/19). Two of the 51 biopsies were positive for non-Hodgkin's lymphoma and one was positive for metastatic renal cell carcinoma. The first-time diagnostic success rate of biopsy was 96.1 % (49/51) and the overall diagnostic success rate and sensitivity were 100 %. All 51 patients were eventually confirmed as having stage IV disease. No serious complications were encountered and the average biopsy time was 30 min. CONCLUSION: PET/CT-guided percutaneous biopsy of 18F-FDG-avid bone metastases is an effective and safe method that yields a high diagnostic success rate in the evaluation of hypermetabolic bone lesions in patients with suspected advanced lung cancer.

Prevalence of dyslipidemia and its control in type 2 diabetes: A multicenter study in endocrinology clinics of China.

OBJECTIVE: The aim of this study was to assess the levels of serum lipid and awareness, treatment, and control of dyslipidemia in type 2 diabetes mellitus (T2DM) patients from top-ranked endocrinology clinics in large cities of China. MATERIALS AND METHODS: A cross-sectional study in a representative sample of 4807 Chinese adults 40 to 75 years of age was conducted during 2010 to 2011 at 20 endocrinology clinics in top-ranked hospitals covering most of the major cities of China. Serum lipid levels were measured, and treatment of dyslipidemia was recorded and assessed. RESULTS: In the present study, the prevalence of dyslipidemia was 67.1% in T2DM subjects. Among those with dyslipidemia, the proportion of awareness and treatment was 68.7% and 55.9%. Among participants with lipid-lowering therapy, 686 subjects achieved the low-density lipoprotein cholesterol (LDL-C) control less than 2.60 mmol/L, with the rate being 39.4%. In those patients with previous cardiovascular disease, the percentage of participants who achieved LDL-C goal (1.80 mmol/L) was 15.3%. CONCLUSION: The prevalence of dyslipidemia is high, and the awareness, treatment, and control of dyslipidemia are relatively low in Chinese T2DM patients. This calls for the awareness and intervention of dyslipidemia in these patients.

The correlation of plasma omentin-1 with insulin resistance in non-obese polycystic ovary syndrome.

OBJECTIVES: Aberrant circulating adipokines are considered to be related to the pathological mechanism of polycystic ovary syndrome (PCOS). This study aims to evaluate the relationship between plasma omentin-1 levels, metabolic and hormonal parameters in the setting of non-obese Chinese women with PCOS. MATERIAL AND METHODS: This was a case-controlled, cross-sectional study of 153 non-obese (BMI<25kg/m(2)) PCOS and 114 age-matched healthy non-obese control individuals. Levels of plasma omentin-1, fasting blood glucose, insulin and sexual hormones and ovary volume were analyzed in all subjects. RESULTS: Plasma omentin-1 levels of non-obese PCOS individuals were significantly lower than in healthy non-obese controls. Body Mass Index (BMI), homeostasis model of assessment for insulin resistance index (HOMA-IR), levels of testosterone, luteinizing hormone (LH) and follicle-stimulating hormone (FSH), LH/FSH ratio and ovary volume (OV) were significantly higher in subjects with PCOS than controls. In the HOMA-IR stratified subgroups, PCOS individuals with insulin resistance had lower omentin-1 than those without insulin resistance after BMI adjustment. Omentin-1 was negatively correlated with BMI, HOMA-IR and fasting insulin. Multiple linear regressions revealed that BMI contributed to omentin-1 levels. Ovary volume was negatively correlated to HOMA-IR but had no correlation with omentin-1. CONCLUSIONS: Plasma omentin-1 concentrations were decreased in the non-obese PCOS group. Insulin resistance could further decrease plasma omentin-1 in non-obese individuals with PCOS independent of BMI status.

Pre-treatment metabolic tumor volume and total lesion glycolysis are useful prognostic factors for esophageal squamous cell cancer patients.

OBJECTIVES: To study application of the maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV) and total lesion glycolysis (TLG) with 18F-FDG PET/CT for predicting prognosis of esophageal squamous cell cancer (ESC) patients. METHODS: Eighty-six patients with ESC staged from I to IV were prospectively enrolled. Cisplatin-based chemoradiotherapy (CCRT) or palliative chemoradiotherapy were the main treatment methods and none received surgery. 18F-FDG PET/CT scans were performed before the treatment. SUVmax, MTV, and TLG were measured for the primary esophageal lesion and regional lymph nodes. Receiver operating characteristic curves (ROCs) were generated to calculate the P value of the predictive ability and the optimal threshold. RESULTS: MTV and TLG proved to be good indexes in the prediction of outcome for the ESC patients. An MTV value of 15.6 ml and a TLG value of 183.5 were optimal threshold to predict the overall survival (OS). The areas under the curve (AUC) for MTV and TLG were 0.74 and 0.70, respectively. Kaplan-Meier analysis showed an MTV less than 15.6 ml and a TLG less than 183.5 to indicate good media survival time (p value <0.05). In the stage III-IV patient group, MTV could better predict the OS (P < 0.001), with a sensitivity and specificity of 0.80 and 0.67, respectively. CONCLUSIONS: Pre-treatment MTV and TLG are useful prognostic factors in non- surgical ESC.

De novo characterization of Japanese scallop Mizuhopecten yessoensis transcriptome and analysis of its gene expression following cadmium exposure.

BACKGROUND: Japanese scallop has been cultured on a large-scale in China for many years. However, serious marine pollution in recent years has resulted in considerable loss to this industry. Moreover, due to the lack of genomic resources, limited research has been carried out on this species. To facilitate the understanding at molecular level immune and stress response mechanism, an extensive transcriptomic profiling and digital gene expression (DGE) database of Japanese scallop upon cadmium exposure was carried out using the Illumina sequencing platform. RESULTS: RNA-seq produced about 112 million sequencing reads from the tissues of adult Japanese scallops. These reads were assembled into 194,839 non-redundant sequences with open reading frame (ORF), of which 14,240 putative amino acid sequences were assigned biological function annotation and were annotated with gene ontology and eukaryotic orthologous group terms. In addition, we identified 720 genes involved in response to stimulus and 302 genes involved in immune-response pathways. Furthermore, we investigated the transcriptomic changes in the gill and digestive gland of Japanese scallops following cadmium exposure using a tag-based DGE system. A total of 7,556 and 3,002 differentially expressed genes were detected, respectively, and functionally annotated with KEGG pathway annotations. CONCLUSION: This study provides a comprehensive transcripts sequence resource for the Japanese scallop and presents a survey of gene expression in response to heavy metal exposure in a non-model marine invertebrate via the Illumina sequencing platform. These results may contribute to the in-depth elucidation of the molecular mechanisms involved in bivalve responses to marine pollutants.

[Serial (18)F-FDG PET-CT imaging during radiotherapy for nasopharyngeal carcinoma: a prospective clinical study].

OBJECTIVE: The primary aim of this prospective study was to use serial (18)F-FDG PET-CT imaging to evaluate the trend of the tumor's maximum standardized uptake value (SUVmax) during radiotherapy (RT) for patients with nasopharyngeal carcinoma (NPC), and to explore the possibility of early evaluation of the tumor bio-metabolic response during radiotherapy. METHODS: Sixty patients with biopsy-proven primary NPC were prospectively enrolled into the study. All patients underwent four (18)F-FDG PET-CT scans: one initial scan before RT/cisplatin based concurrent chemoradiotherapy, at the point of 50 Gy during RT, the end of RT, and one month after RT, respectively. Tumor (18)F-FDG uptake was analyzed according to the World Health Organization pathological type. RESULTS: There was a significant difference (P < 0.001) of the mean of SUVmax of the primary site among pretreatment (11.20 ± 5.37) and posttreatment at the dose of 50 Gy (3.50 ± 1.59), at the end of RT (3.05 ± 1.56) and one month after RT (2.52 ± 1.46). There was also a significant difference (P < 0.001) of the mean of SUVmax of neck node site. However, there was a significant difference of the SUVmax between histological WHO type IIb and type IIa in the primary site (P = 0.046) [(67 ± 19)% reduction at dose 50 Gy for type IIb vs. (55 ± 24)% for type IIa] but not in the lymph nodes. CONCLUSIONS: Early PET scan during or right after RT instead of conventional 3 months interval after RT is indicated to evaluate the tumor response and to develop individualized adaptive radiotherapy in NPC. Our next study will attempt to demonstrate the results based on long-term follow-up data.

The role of a workflow in diagnosing biliary causes for acute pancreatitis / 中华内科杂志

ObjectiveTo establish a practical and effective clinical pathway (CP) for the etiological diagnosis of acute biliary pancreatitis.MethodsA total of 2216 patients enrolled were randomly divided into control group (n =1120) and CP group (n =1096) according to different etiological diagnosis methods including following doctor's established experiences and habits and the designed CP in our study.ResultsThere was no significant difference in baseline data between the two groups.The etiology of acute pancreatitis was determined in 91.1％ (999/1096) of cases in the CP group which was significantly higher than the control group (65.5 ％,734/1120),P ＜ 0.05.The enhanced etiological determination of CP group was mainly consisted of the increased detection of biliary stones,duodenal diseases as well as pancreas divisum,P ＜ 0.05.The positive etiological determination of magnetic resonance cholangiopancreatography and endoscopic retrograde cholangiopancreatography in the CP group were 59.1％ (273/462) and 86.0％ (98/114),respectively.ConclusionsThe CP established in this study significantly enhances the biliary etiological determination of acute pancreatitis. It is easy to be conducted and may be of importance to improve the quality of etiological diagnosis of acute pancreatitis.

Multiple primary malignant tumors of upper gastrointestinal tract: a novel role of 18F-FDG PET/CT.

AIM: To evaluate the capacity of (18)F-fluorodeoxyglucose positron emission tomography/computed tomography ((18)F-FDG PET/CT) for detecting multiple primary cancer of upper gastrointestinal (UGI) tract. METHODS: Fifteen patients (12 without cancer histories and 3 with histories of upper GI tract cancer) were investigated due to the suspicion of primary cancer of UGI tract on X-ray barium meal and CT scan. Subsequent whole body (18)F-FDG PET/CT scan was carried out for initial staging or restaging. All the patients were finally confirmed by endoscopic biopsy or surgery. The detection rate of multiple primary malignant cancers was calculated based on (18)F-FDG PET/CT and endoscopic examinations. RESULTS: (18)F-FDG PET/CT scan was positive in 32 suspicious lesions, 30/32 were true positive primary lesions, and 2/32 were false positive. In 15 suspicious lesions with negative (18)F-FDG PET/CT scan, 12/15 were true negative and 3/15 were false negative. Among the 15 patients, 12 patients had 29 primary synchronous tumors confirmed by pathology, including 8 cases of esophageal cancers accompanied with gastric cancer and 4 of hypopharynx cancers with esophageal cancer. The other 3 patients had 4 new primary metachronous tumors, which were multiple primary esophageal cancers. PET/CT imaging detected local lymph node metastases in 11 patients. Both local lymph node metastases and distant metastases were detected in 4 patients. On a per-primary lesion basis, the sensitivity, specificity, accuracy, negative predictive value and positive predictive value of (18)F-FDG PET/CT for detecting multiple primary cancer of UGI tract were 90.9%, 85.7%, 89.4%, 80% and 93.7%, respectively. CONCLUSION: The whole body (18)F-FDG PET/CT may play an important role in evaluating the multiple primary malignant tumors of UGI tract cancer.

[The effects of early intensive therapy on islet beta cell function and long-term glycemia control in newly diagnosed type 2 diabetic patients with different fasting plasma glucose levels.].

OBJECTIVE: To investigate the effects of early intensive therapy on beta cell function and long-term glycemic control in newly diagnosed type 2 diabetic patients with different recruiting fasting plasma glucose (FPG) levels. METHODS: A total of 382 newly diagnosed type 2 diabetic patients with FPG 7.0 - 16.7 mmol/L were randomly assigned to therapy with insulin in the form of continuous subcutaneous insulin infusion (CSII) or multiple daily injection (MDI) or oral hypoglycemic agents (OHA, by using gliclazide and/or metformin) for initial rapid correction of hyperglycemia. The treatments were stopped after euglycemia had been maintained for 2 weeks. The patients were followed longitudinally on diet alone for 1 year. Intravenous glucose tolerances tests (IVGTTs) were performed and blood glucose, insulin and proinsulin were measured before and after therapy as well as at 1-year follow-up. Homeostasis model assessment (HOMA) of beta cell function and insulin resistance index (HOMA-beta and HOMA-IR) were calculated. All the patients were stratified on the recruiting FPG: stratum A (7.0 mmol/L

Clinical usefulness of 18F-FDG PET/CT in the restaging of esophageal cancer after surgical resection and radiotherapy.

AIM: To evaluate the clinical usefulness of (18)F-fluorodeoxyglucose positron emission and computed tomography ((18)F-FDG PET/CT) in restaging of esophageal cancer after surgical resection and radiotherapy. METHODS: Between January 2007 and Aug 2008, twenty histopathologically diagnosed esophageal cancer patients underwent 25 PET/CT scans (three patients had two scans and one patient had three scans) for restaging after surgical resection and radiotherapy. The standard reference for tumor recurrence was histopathologic confirmation or clinical follow-up for at least ten months after (18)F-FDG PET/CT examinations. RESULTS: Tumor recurrence was confirmed histopathologically in seven of the 20 patients (35%) and by clinical and radiological follow-up in 13 (65%). (18)F-FDG PET/CT was positive in 14 patients (68.4%) and negative in six (31.6%). (18)F-FDG PET/CT was true positive in 11 patients, false positive in three and true negative in six. Overall, the accuracy of (18)F-FDG PET/CT was 85%, negative predictive value (NPV) was 100%, and positive predictive value (PPV) was 78.6%. The three false positive PET/CT findings comprised chronic inflammation of mediastinal lymph nodes (n = 2) and anastomosis inflammation (n = 1). PET/CT demonstrated distant metastasis in 10 patients. (18)F-FDG PET/CT imaging-guided salvage treatment in nine patients was performed. Treatment regimens were changed in 12 (60%) patients after introducing (18)F-FDG PET/CT into their conventional post-treatment follow-up program. CONCLUSION: Whole body (18)F-FDG PET/CT is effective in detecting relapse of esophageal cancer after surgical resection and radiotherapy. It could also have important clinical impact on the management of esophageal cancer, influencing both clinical restaging and salvage treatment of patients.

Clinical value of F-FDG PET/CT in assessing suspicious relapse after rectal cancer resection.

AIM: To evaluate the value of (18)F-fluorodeoxyglucose positron emission tomography/computed tomography ((18)F-FDG PET/CT) in the restaging of resected rectal cancer. METHODS: From January 2007 to Sep 2008, 21 patients who had undergone curative surgery resection for rectal carcinoma with suspicious relapse in conventional imaging or clinical findings were retrospectively enrolled in our study. The patients underwent 28 PET/CT scans (two patients had two scans, one patient had three and one had four scans). Locoregional recurrences and/or distant metastases were confirmed by histological analysis or clinical and imaging follow-up. RESULTS: Final diagnosis was confirmed by histopathological diagnosis in 12 patients (57.1%) and by clinical and imaging follow-up in nine patients (42.9%). Eight patients had extrapelvic metastases with no evidence of pelvic recurrence. Seven patients had both pelvic recurrence and extrapelvic metastases, and two patients had pelvic recurrence only. (18)F-FDG PET/CT was negative in two patients and positive in 19 patients. (18)F-FDG PET/CT was true positive in 17 patients and false positive in two. The accuracy of (18)F-FDG PET/CT was 90.5%, negative predictive value was 100%, and positive predictive value was 89.5%. Five patients with perirectal recurrence underwent (18)F-FDG PET/CT image guided tissue core biopsy. (18)F-FDG PET/CT also guided surgical resection of pulmonary metastases in three patients and monitored the response to salvage chemotherapy and/or radiotherapy in four patients. CONCLUSION: (18)F-FDG PET/CT is useful for evaluating suspicious locoregional recurrence and distant metastases in the restaging of rectal cancer after curative resection.

Metabolic restaging of hepatocellular carcinoma using whole-body F-FDG PET/CT.

AIM: To evaluate the ability of (18)F-fluorodeoxyglucose positron emission and computed tomography ((18)F-FDG PET/CT) in restaging of hepatocellular carcinoma (HCC) after treatment. METHODS: We reviewed a database of the diagnostic performance of (18)F-FDG PET/CT scan for patients with HCC following local or regional treatment. The database consisted of (18)F-FDG PET/CT information of 21 male and 4 female (age range, 27-81 years; mean age, 51.6 years) patients who had received surgical resection and/or interventional treatments and then underwent (18)F-FDG PET/CT scan. All patients had received enhanced CT scan of the liver two weeks before or after the (18)F-FDG PET/CT scan. Intrahepatic recurrence and/or extrahepatic metastases were confirmed by histological analysis or clinical and imaging follow-up. The accuracy of (18)F-FDG PET/CT study was determined by histopathological results or by clinical and imaging follow-up. RESULTS: (18)F-FDG PET/CT was abnormal in 19 of the 25 (76.0%) patients. In detecting HCC recurrence, (18)F-FDG PET/CT scored 17 true positives, 5 true negatives, 2 false positives and 1 false negative. The sensitivity, specificity and accuracy of (18)F-FDG PET/CT in detecting HCC recurrence was 89.5%, 83.3% and 88%, respectively. (18)F-FDG PET/CT had an impact on management of these patients by settling the problem of an unexplained increase in alpha-fetoprotein after treatment (14 patients), by monitoring response to the treatment and guiding additional regional therapy (12 patients), by identifying extrahepatic metastases (10 patients), by identifying tumor growth or thrombosis in the portal vein (6 patients), or by guiding surgical resection of extrahepatic metastases (2 patients). CONCLUSION: Our results suggest that whole body (18)F-FDG PET/CT may be useful in the early evaluation of residual, intrahepatic recurrent or extrahepatic metastatic lesions and able to provide valuable information for the management of HCC recurrence.