Targeting insulin inhibition as a metabolic therapy in advanced cancer: A pilot safety and feasibility dietary trial in 10 patients

ObjectiveMost aggressive cancers demonstrate a positive positron emission tomographic (PET) result using ¹⁸F-2-fluoro-2-deoxyglucose (FDG), reflecting a glycolytic phenotype. Inhibiting insulin secretion provides a method, consistent with published mechanisms, for limiting cancer growth.MethodsEligible patients with advanced incurable cancers had a positive PET result, an Eastern Cooperative Oncology Group performance status of 0 to 2, normal organ function without diabetes or recent weight loss, and a body mass index of at least 20 kg/m². Insulin inhibition, effected by a supervised carbohydrate dietary restriction (5% of total kilocalories), was monitored for macronutrient intake, body weight, serum electrolytes, β-hydroxybutyrate, insulin, and insulin-like growth factors-1 and -2. An FDG-PET scan was obtained at study entry and exit.ResultsTen subjects completed 26 to 28 d of the study diet without associated unsafe adverse effects. Mean caloric intake decreased 35 ± 6% versus baseline, and weight decreased by a median of 4% (range 0.0–6.1%). In nine patients with prior rapid disease progression, five with stable disease or partial remission on PET scan after the diet exhibited a three-fold higher dietary ketosis than those with continued progressive disease (n = 4, P = 0.018). Caloric intake (P = 0.65) and weight loss (P = 0.45) did not differ in those with stable disease or partial remission versus progressive disease. Ketosis was associated inversely with serum insulin levels (P = 0.03).ConclusionPreliminary data demonstrate that an insulin-inhibiting diet is safe and feasible in selected patients with advanced cancer. The extent of ketosis, but not calorie deficit or weight loss, correlated with stable disease or partial remission. Further study is needed to assess insulin inhibition as complementary to standard cytotoxic and endocrine therapies.     

Racial Diversity Among Histology of Renal Cell Carcinoma at an Urban Medical Center

BackgroundNon-Hispanic blacks (NHB) with renal cell carcinoma (RCC) are more likely to have papillary RCC (pRCC) than non-Hispanic whites (NHW). Data on histologic subtypes in RCC in Hispanics (H) are also sparse. Previous studies have shown that pRCC is more prevalent in NHB than in NHW, but they analyzed predominantly NHW populations. The Montefiore–Einstein Center for Cancer Care (MECC) serves a predominantly NHB and H population in the Bronx, NY. We investigated histologic subtype specific associations with established RCC risk factors in this population.Patients and MethodsThe MECC tumor registry was used to identify patients ≥ 18 years of age treated with partial or radical nephrectomy between January 2000 and December 2015. An institutional software program and individual chart review were used to obtain demographic data (including self-reported race, age, and sex), pathology data, and RCC risk factors (hypertension, diabetes, renal function, weight). Data were modeled by multinomial logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs).ResultsA total of 1010 RCC cases were identified. Of these, 232 (23.0%) occurred in NHW, 383 (37.9%) NHB, 181 (17.9%) H, and 214 (21.2%) other. A total of 530 cases (52.5%) were clear cell (ccRCC) histology, 257 (25.4%) pRCC, 100 (9.9%) chromophobe (cRCC), and 123 (12.2%) other. Individuals with pRCC compared to ccRCC were more likely to be NHB than NHW (OR, 4.41; 95% CI, 2.81-6.93) but were less likely to be female (OR, 0.50; 95% CI, 0.35-0.72). Individuals with pRCC were also less likely to be H than NHW (OR, 0.52; 95% CI, 0.27-0.99). Patients with cRCC were also more likely to be NHB than NHW (OR, 2.23; 95% CI, 1.06-4.67).ConclusionIn the MECC data set, histology of RCC varies by race, confirming earlier reports that non-ccRCC is more common in NHB than NHW. We also report that pRCC is less common in H than NHW.     

单孔腹腔镜阑尾切除术的常见困难与处理

目的:探讨经脐单孔腹腔镜行阑尾切除的手术中的常见困难与处理方法。方法:回顾性分析勒流医院2009年6月—2012年2月采取经脐单孔腹腔镜治疗的86例阑尾炎患者的临床资料。结果:处理困难包括腹腔脓液积聚15例,阑尾显露困难6例,残端处理困难5例,腹腔粘连3例;78例在单孔腹腔镜下完成手术,8例转为常规腹腔镜手术,无中转开腹者;手术时间(41.39±13.76)min,住院时间(4.82±2.16)d;全组无术后出血、切口感染等并发症。结论:单孔腹腔镜行阑尾切除手术是安全可行的;阑尾切除困难时,应视阑尾病变的情况采取相应的方法和技巧,能有效的防止并发症的发生。     

妊娠不同时期孕妇对运动的认知及现状调查

目的了解妊娠不同时期孕妇对运动的认知程度及运动方式,为进一步有针对性地指导孕妇合理运动提供依据。方法采用便利抽样的方法,选取成都市某妇女儿童专科医院门诊进行产前检查的妊娠早期、中期、晚期孕妇各396例,采用自行设计的问卷进行运动认知及运动方式调查。结果 55.30%孕妇能认识到孕期不合理运动的危害,82.36%能认识到孕期合理运动的好处,55.73%有信心进行孕期运动,但同时也面临着不同程度的障碍,如个人习惯、工作太忙、对运动知识不了解等;散步和爬楼梯是孕妇最主要的运动方式;不同妊娠时间孕妇散步、慢跑、游泳参与率比较,差异有统计学意义(P<0.05,P<0.01)。结论大多数孕妇能认识到孕期合理运动的好处以及不合理运动的危害,且有信心进行运动,但仍受多种因素的影响;同时,孕妇的运动方式过于单一,存在安全顾虑。医护人员应加大孕期运动安全的指导,结合孕妇的实际情况,指导其选择安全、有效的孕期运动方式。     

Tuberculosis case-finding through a village outreach programme in a rural setting in southern Ethiopia: community randomized trial

OBJECTIVE: To ascertain whether case-finding through community outreach in a rural setting has an effect on case-notification rate, symptom duration, and treatment outcome of smear-positive tuberculosis (TB). METHODS: We randomly allocated 32 rural communities to intervention or control groups. In intervention communities, health workers from seven health centres held monthly diagnostic outreach clinics at which they obtained sputum samples for sputum microscopy from symptomatic TB suspects. In addition, trained community promoters distributed leaflets and discussed symptoms of TB during house visits and at popular gatherings. Symptomatic individuals were encouraged to visit the outreach team or a nearby health facility. In control communities, cases were detected through passive case-finding among symptomatic suspects reporting to health facilities. Smear-positive TB patients from the intervention and control communities diagnosed during the study period were prospectively enrolled. FINDINGS: In the 1-year study period, 159 and 221 cases of smear-positive TB were detected in the intervention and control groups, respectively. Case-notification rates in all age groups were 124.6/10(5) and 98.1/10(5) person-years, respectively (P = 0.12). The corresponding rates in adults older than 14 years were 207/10(5) and 158/10(5) person-years, respectively (P = 0.09). The proportion of patients with >3 months' symptom duration was 41% in the intervention group compared with 63% in the control group (P<0.001). Pre-treatment symptom duration in the intervention group fell by 55-60% compared with 3-20% in the control group. In the intervention and control groups, 81% and 75%, respectively of patients successfully completed treatment (P = 0.12). CONCLUSION: The intervention was effective in improving the speed but not the extent of case finding for smear-positive TB in this setting. Both groups had comparable treatment outcomes.     

Randomized phase II trial of embolization therapy versus chemoembolization therapy in previously treated patients with colorectal carcinoma metastatic to the liver

Locoregional therapies are useful in treating patients with colorectal cancer metastatic to the liver. A prospective randomized phase II trial of hepatic artery embolization versus hepatic artery chemoembolization was conducted to evaluate the response rates and toxicities of these therapies in the second-line setting. Patients were required to have biopsy-proven adenocarcinoma of the colon or rectum metastatic to the liver, with the liver as the sole or predominant site of metastatic disease. All patients had measurable disease and had failed at least one prior systemic chemotherapy treatment for metastatic disease. Patients were randomized to receive either embolization therapy with polyvinyl alcohol foam (Ivalon) administered as a single agent or chemoembolization using polyvinyl alcohol foam mixed with 750 mg/m2 of 5-fluorouracil and 9 million units of interferon. Drugs and embolic material were administered via the hepatic artery as a slurry with polyvinyl alcohol foam. Fifty eligible patients were enrolled. There were 24 patients in the chemoembolization arm and 26 in the embolization arm. Sixty-four percent of patients in both treatment arms had the liver as the sole metastatic site. The most common National Cancer Institute common toxicity criteria grade 3/4 toxicities were diarrhea (17%) and hepatic toxicity (8%). There was 1 (4%) treatment-related mortality due to a hepatic abscess. Four patients (15.4%) treated with embolization had a partial response (PR), and 5 patients (20.8%) treated with chemoembolization had a PR. The median survival for all patients was 11 months (95% confidence interval [CI], 8-15 months). Survival in patients with extrahepatic disease was 8 months (95% CI, 6-10 months). Survival in patients with liver-only metastases was 15 months (95% CI, 10-17 months). Embolization of the liver as second-line therapy in patients with liver-predominant metastases is safe and effective. Median survivals are comparable to other second-line therapies     

浙贝母提取工艺的优化选择

以总生物碱含量为指标,采用正交试验法考察提取溶媒,溶媒浓度,药材处理方法、提取次数等因素对总生物碱提取效果的影响。结果表明,浙贝母的最佳提取工艺条件为９５％乙醇提取２次,每次１ｈ,整粒提取,溶媒量６倍,药材不需碱处理。     

Global proteomic analysis distinguishes biologic differences in head and neck squamous carcinoma

The goal of this study was to establish a method for detecting biologically significant differences in protein expression of head and neck squamous cell carcinoma (HNSCC) obtained from the same samples utilized in gene expression analyses. Proteins from two head and neck tumor cell lines, SCC-25 and FaDu, were isolated from the denatured protein solution remaining from the TRIzol extraction procedure used for isolation of total RNA for microarray analysis. Peptides resulting from chemical and enzymatic digestion of the proteins were first separated by strong cation-exchange chromatography, followed by liquid chromatography-mass spectrometry (LC-MS) analysis on a QqTOF mass spectrometer. Stable isotope-labeled synthetic peptides were added to each ion-exchange fraction as internal standards, for reversed-phase HPLC retention time alignment. Protein extraction and digestion were repeated three times for each cell line and each extract was analyzed three times by LC-MS. To discriminate between technical vs biological variation, the ion-exchange fraction, retention time, normalized mass and signal intensity of these nine data sets were constructed into numerical arrays for statistical analysis. Of the approximately 50,000 signals, 90 peptide ions were found to discriminate the two cell lines with high stringency. Of those, six peptides were derived from vimentin and four peptides were derived from annexin II; both expressed more in SCC-25. Follow-up analysis of some of these signals by LC-MS/MS and RNA expression profiling revealed both concordance and discordance of RNA and protein expression. This study demonstrates that this procedure is highly reliable for identifying peptides that distinguish biological variability among samples, indicating that this method can be applied to study clinical samples, to identify potential prognostic biomarkers for HNSCC.