What are the current and potential future roles for endoscopic ultrasound in the treatment of pancreatic cancer?

Pancreatic adenocarcinoma is the fourth leading cause of cancer-related death in the United States. Due to the aggressive tumor biology and late manifestations of the disease, long-term survival is extremely uncommon and the current 5-year survival rate is 7%. Over the last two decades, endoscopic ultrasound(EUS) has evolved from a diagnostic modality to a minimally invasive therapeutic alternative to radiologic procedures and surgery for pancreatic diseases. EUSguided celiac plexus intervention is a useful adjunct to conventional analgesia for patients with pancreatic cancer. EUS-guided biliary drainage has emerged as a viable option in patients who have failed endoscopic retrograde cholangiopancreatography. Recently, the use of lumen-apposing metal stent to create gastrojejunal anastomosis under EUS and fluoroscopic guidance in patients with malignant gastric outlet obstruction has been reported. On the other hand, anti-tumor therapies delivered by EUS, such as the injection of anti-tumor agents, brachytherapy and ablations are still in the experimental stage without clear survival benefit. In this article, we provide updates on well-established EUS-guided interventions as well as novel techniques relevant to pancreatic cancer.     

A multicenter study of romiplostim for chemotherapy-induced thrombocytopenia in solid tumor s and hematologic malignancies

Chemotherapy-induced thrombocytopenia (CIT) frequently complicates cancer treatment causing chemotherapy treatment delays, dose reductions, and discontinuation. There is no US Food and Drug Administration (FDA)-approved agent available to manage CIT. This study retrospectively evaluated patients with CIT treated on institutional romiplostim treatment pathways at four US centers. The primary outcome was achievement of a romiplostim response (median on-romiplostim platelet count ≥75x10⁹/L and ≥30x10⁹/L above baseline). Secondary outcomes included time to platelet count ≥100x10⁹/L and rates of the following: platelet count <100×10⁹/L, platelet count <75x10⁹/L, platelet count <50x10⁹/L, thrombocytosis, chemotherapy dose reduction/treatment delay, platelet transfusion, bleeding, and thromboembolism. Multivariable regression was used to identify predictors of romiplostim non-response and compare weekly dosing with intracycle/intermittent dosing. A total of 173 patients (153 solid tumor, 20 lymphoma or myeloma) were treated, with 170 (98%) receiving a median of four (range: 1-36) additional chemotherapy cycles on romiplostim. Romiplostim was effective in solid tumor patients: 71% of patients achieved a romiplostim response, 79% avoided chemotherapy dose reductions/treatment delays, and 89% avoided platelet transfusions. Median per-patient platelet count on romiplostim was significantly higher than baseline (116x10⁹/L vs. 60x10⁹/L; P<0.001). Bone marrow (BM) tumor invasion, prior pelvic irradiation, and prior temozolomide exposure predicted romiplostim non-response. Bleeding rates were lower than historical CIT cohorts and thrombosis rates were not elevated. Weekly dosing was superior to intracycle dosing with higher response rates and less chemotherapy dose reductions/treatment delays/bleeding; intracycle dosing had an incidence rate ratio (IRR) for dose reduction/treatment delay of 3.00 (95%CI: 1.30-6.91; P=0.010) and an IRR for bleeding of 4.84 (95%CI: 1.18-19.89, P=0.029) compared with weekly dosing. Blunted response (10% response rate) was seen in non-myeloid hematologic malignancy patients with BM involvement. In conclusion, romiplostim was safe and effective for CIT in most solid tumor patients.     

INSL5-Deficient Mice Display an Alteration in Glucose Homeostasis and an Impaired Fertility

Insulin-like factor 5 (INSL5), a member of the insulin superfamily, is expressed in the colorectum and hypothalamus. To facilitate studies into the role of INSL5, we generated Insl5(-/-) mice by gene targeting. Insl5(-/-) mice were born in the expected Mendelian ratio, reached normal body weight, but displayed impaired male and female fertility that are due to marked reduction in sperm motility and irregular length of the estrous cycle. Furthermore, Insl5(-/-) mice showed impairment in glucose homeostasis with characteristic elevation of serum glucose levels at an advanced age. Glucose and insulin tolerance tests revealed that the increased blood glucose in Insl5(-/-) mice was due to glucose intolerance resulting from reduced insulin secretion. Morphometric and immunohistological analyses revealed that the Insl5(-/-) mice had markedly reduced average islets area and β-cell numbers. Furthermore, immunohistochemistry showed the expression of INSL5 in enteroendocrine cells in the colorectal epithelium and the presence of its putative receptor relaxin family peptide receptor 4 in pancreatic islet cells. These results suggest the potential role of INSL5 signaling in the regulation of insulin secretion and β-cell homeostasis.     

Prevalence and correlates of snoring in adolescents

Snoring can occur alone or it may be the presenting feature of Obstructive Sleep Apnea and other common chronic conditions. In our study, we aimed to estimate the prevalence and correlates of snoring in adolescent students in Tehran, Iran. A cross-sectional study was designed and students were selected from 20 secondary and high schools, in 5 different zones in Tehran in order to have a representative sample of the adolescent population. A total of 2900 students (1200 male and 1700 female students) 11-17 year-old who were attending secondary and high schools were investigated. Information was collected via a structured face-to-face interview, based on a questionnaire. In addition to snoring, nocturnal cough, asthma-related symptoms, and daytime symptoms were also questioned. BMI was measured by two trained physicians. The prevalence of snoring was 7.9% (4.8% in girls and 12.4% in boys). The prevalence of snoring was significantly higher among males (P< 0.05). Snoring was positively associated with asthma and nocturnal cough. Overweight/obese adolescents had significantly higher rates of snoring and asthma symptoms. Prevalence of daytime symptoms increased significantly in the snoring group.These results suggest that snoring is associated with multiple factors in adolescents. We conclude that the prevalence of snoring is relatively high in children of this region. This highlights the need for awareness among physicians about the problem of sleep-disordered breathing, especially in children with asthma and obesity, and also the need for further studies to measure the prevalence of sleep breathing disorders among Iranians.     

中医辨证治疗慢性肾功能衰竭57例临床观察

目的 :观察中医辨证分型治疗慢性肾功能衰竭(CRF)的临床疗效。方法 :采用中医辨证治疗和正常组对照 ,观察其疗效及血清BUN与Cr的变化。结果 :气阴两虚型、肝肾阴虚型以肾功能代偿期及氮质血症期为主 ;脾肾气(阳)虚型以氮质血症期及尿毒症期为多 ;阴阳两虚型以尿毒症期为最多。各型BUN与Cr明显高于正常组 ,而以阴阳两虚型最高 ;气阴两虚型、肝肾阴虚型、脾肾气(阳)虚型的疗效及降低BUN与Cr作用尤为显著。结论 :CRF患者各型与西医肾功能分期关系密切 ,中医辨证治疗对CRF有明显的改善作用。     

Genetic characterization of two low pathogenic avian influenza virus H5N1 isolates from Ontario, Canada

Genomes of two low pathogenic H5N1 avian influenza (LPAI) viruses, A/Turkey/ON/84/1983 and A/Mallard/ON/499/2005 from Ontario, Canada were cloned and genetically characterized. Phylogenetic analysis showed that the Canadian isolates cluster with other North American AIVs and are distinct from the Euro-Asian H5N1 isolates. Individual gene comparisons demonstrated that the Ontario isolates were most similar to the viruses isolated from around the same time period and geographical area. A long deletion of 22 amino acids was identified in the stalk region of NA of A/Turkey/ON/84/1983 isolate, a characteristic mutation related to its adaptation to domestic birds. To our knowledge A/Turkey/ON/84/1983 genomic sequence is the first and only available entire genomic sequence of a H5N1 AIV from domestic birds in Canada and USA. This work is a joint collaboration between the principal investigators Davor Ojkic and Shayan Sharif.     

In vitro assessment of the trackability of neurovascular intermediate catheters: a comparative analysis

The advent of new flexible intermediate catheters facilitated manual aspiration thrombectomy (MAT) for treating neurovascular ischaemic diseases. While these catheters are somewhat flexible, most catheters were not designed specifically for aspiration. Trackability is an important property of catheters facilitating catheter advancement in highly tortuous cerebrovasculature. In this study, a novel in vitro trackability test system has been developed using micro pressure transducers and silicone tubes. The exerted force from the catheter tips were quantitatively evaluated while the catheter passed the curved regions. The trackability of three different types of catheters were compared, i.e. Penumbra 054, Concentric DAC 057 and Reverse Reflex. The exerted forces obtained from the first sensor (Sensor 1) during passing the second curve showed the maximum values through the entire transcatheter procedure. When compared, the exerted forces were least for the Penumbra 054 (0.272?±?0.012?N), representing highly trackable systems in highly tortuous vessel navigation.