Unveiling the mechanisms of immune evasion in pancreatic cancer: may it be a systemic inflammation responsible for dismal survival?

Clinical and Translational Oncology - Pancreatic cancer (PC) is one of the most aggressive malignancies with no effective treatment if diagnosed in advanced stage. Systemic inflammation is a...     

Double germline mutations in the RET Proto-oncogene in MEN 2A and MEN 2B kindreds.

Medullary thyroid carcinoma (MTC) is a rare form of thyroid cancer representing about 10% of all thyroid malignancies. It occurs mostly as a sporadic tumor or in association with autosomal dominant inherited cancer syndromes--multiple endocrine neoplasia (MEN) types 2A and 2B and familial MTC. Germline mutations in exons 8, 10, 11, 13, 14, 15 and 16 of the RET proto-oncogene are found in most of the familial cases. There are only a few published data reporting multiple germline mutations in the RET proto-oncogene. We have detected double germline mutations in 2 different exons on the same RET allele in two MEN 2 families. In the MEN 2A family, double germline mutation in exons 10 (Cys620Phe) and 13 (Tyr791Phe) was detected. In the MEN 2B family, beside the classical germline mutation in exon 16 (Met918Thr) a second germline mutation in exon 13 (Tyr791Phe) was found. This study revealed that MEN 2 syndromes can also be caused by double germline mutations in the RET proto-oncogene and these families can be added to small worldwide cohort of families with multiple germline mutations.     

The relative utilization of eicosapentaenoic and arachidonic acids by the 1-acylgycerophosphorylcholine and the 1-acylglycerophosphorylinositol acyltransferase pathways in human platelet microsomes

The relative entry of eicosapentaenoic acid (EPA) and arachidonic acid (AA) via 1-acylglycerophosphorylcholine and 1-acylglycerophosphorylinositol acyltransferase activity into phosphatidylcholine (PC) and phosphatidylinositol (PI), respectively, was studied in human platelets. A known mixture of [¹⁴C]EPA and [³H]AA along with an acyl-CoA generating system and lyso-acceptor phospholipids were incubated with a platelet mixed membrane preparation. The radioactivities in the products were determined following lipid extraction and thin-layer chromatographic separations. The [³H]AA/[¹⁴C]EPA ratios in the products, PC and PI, indicated some preference of both acyltransferase pathways for EPA over AA at 50 μM exogenously-added lysoPC or lysoPI. Altering the concentration of lysoPC (10–50 μM) did not significantly affect the selectivity for EPA. In contrast, reducing the concentration of lysoPI from 50 μM to 10 μM changed the selectivity of the acyltransferase pathway from favouring EPA to slightly favouring AA. The presence of a mixture of lysoPC and lysoPI resulted in a partitioning of EPA more towards PC and less towards PI which may account, in some part, for the greater AA/EPA mass ratio observed in the PI from human subjects consuming fish oil. The magnitude of the differences between PC and PI in their AA/EPA mass ratios observed in vivo, however, cannot be explained by the selectivity demonstrated herein by the acyltransferase pathways.     

Case report: passively acquired anti-D in a D+ pregnant patient

A sample was submitted for serologic evaluation from a pregnant patient with immune thrombocytopenic purpura (ITP) for possible transfusion in the future because of a decreased platelet count. Anti-D and -E were identified in the patient's serum using several antibody identification techniques, and anti-D was recovered in an acid eluate prepared from the patient's red cells. It was discovered that WinRho had been administered to treat the ITP. This product has been licensed for treatment of nonsplenectomized D+ children and adults with ITP to increase the platelet count. Administration of anti-D to D+ individuals for treatment of ITP can cause a red cell anemia.     

Toxicological evaluation of dietary diazinon in the rat

Female Wistar rats were fed a semi-purified diet containing either no pesticide or 0.1 to 15 ppm diazinon for up to 92 days. At specified times, animals were bled from the orbital sinus to facilitate measurement of plasma and erythrocyte cholinesterase activity using a highly sensitive radiometric assay. Additional rats were sacrificed to determine brain acetylcholinesterase activity. General nutritional parameters measured included body weight gains and feed consumption during the growing period. Feeding diazinon at the levels employed produced no visible toxic manifestations. Treated animals showed weight gains and feed consumption which were comparable to appropriate controls. Feeding trials up to 90 days revealed that rats were highly sensitive to diazinon after 31 to 35 days exposure, as judged by reduction of plasma and erythrocyte cholinesterase activities. Brain acetylcholinesterase was judged to be insensitive to dietary diazinon (1.0 to 15 ppm), although moderate reduction (by 6%) of brain enzyme activity was noted among animals fed 10 ppm diazinon at Day 92. For all feeding trials, plasma cholinesterase was a more sensitive indicator of diazinon toxicity compared to erythrocyte or brain acetylcholinesterase. The no effect level of diazinon for the rat was judged to be 0.1 ppm in the diet, which translates into an equivalent daily intake of 9 g/kg body weight/day. This no effect level is 20- to 50-fold lower than levels reported elsewhere in the literature, which may be attributed, in part, to the use of female animals in the present studies.     

Laparoscopic surgical staging for uterine malignancies using harmonic shears (UltraCision) in comparison to electrosurgery: operative technique, feasibility and complications

This retrospective study assesses and compares perioperative parameters in two groups of patients treated by different operative techniques of laparoscopic surgical staging (LASS) for uterine cancer. Between April 1996 and May 2005, 119 consecutively selected women with cervical cancer (n=30) or clinical stage I endometrial cancer (n=89) underwent laparoscopic assisted vaginal hysterectomy (LAVH), total laparoscopic hysterectomy (TLH) or radical laparoscopic assisted vaginal hysterectomy (RALVH) plus bilateral salpingo-oophorectomy (BSO) and/or lymph node dissection (LND) during a primary surgical procedure using an electrosurgery (ELC, n=37) or ultrasonic (US, n=82) operative technique (harmonic shears, UltraCision). The UltraCision was used as a primary method of dissection and hemostasis from 1999. We were unable to perform prompt and thorough hemostasis in 2 patients from the US group (successful procedure rate 97.5%) because of ineffective post-ultrasonic coagulation of venous paravaginal varices (RALVH procedure) and of vena ovarica varices (LAVH, BSO procedure). The UltraCision was effective in all cases of lymphadenectomy. Successful procedure rate of the ELC operative technique was 100%. There were no statistically significant differences between the groups with regard to operation time, blood loss, hospital stay, and complications. There was a significant difference (P<0.001) in the number of lymph nodes harvested: a mean of 18.1 in the US group and 13.7 in the ELC group. We think that the difference was influenced by an increase in experience with laparoscopic lymph node dissection. The UltraCision operative technique ensures efficient dissection, coagulation, cutting, and grasping for LASS in women with cervical and endometrial cancer.     

Protracted neurocardiogenic reaction

Vasovagal reactions following catheterization procedures are relatively common complications, mostly in their milder forms. We present a case report of a young male undergoing selective coronarography with a dramatic postprocedural course including haemodynamic instability, and especially very late normalization of the neurological status.     

Prevalence of polyps greater than 9 mm in a consortium of diverse clinical practice settings in the United States.

BACKGROUND & AIMS: Colonoscopy is often performed with the goal of identification of patients with serious colon neoplasia. We determined the prevalence of colon masses or polyps greater than 9 mm on the basis of age, gender, race, and procedure indication in diverse clinical practice settings and compared occurrence in patients receiving colonoscopy for screening, surveillance, or evaluation of symptoms. METHODS: We obtained patient demographics, procedure indication, and endoscopic findings from colonoscopy reports in the Clinical Outcomes Research Initiative data repository, which receives endoscopy reports from 73 diverse practice sites in the United States. A multivariate model was developed to measure risk variables for a mass or polyps >9 mm. Absolute risk was calculated in the model on the basis of the number needed to endoscope (NNE) to identify 1 patient with a mass or polyp >9 mm. RESULTS: From 2000-2002, colonoscopies in 141,413 unique patients were analyzed. Sixty-nine percent of the reports came from private practice (nonacademic) settings. Increasing age, male gender, and black race were associated with increased risk of mass or polyps >9 mm. In the 50- to 59-year-old average-risk group, 28 women and 18 men would need to have screening colonoscopy to identify 1 patient with a mass/polyp >9 mm. Patients with positive fecal occult blood test results, hematochezia, and anemia had lower NNE, whereas men older than 60 years receiving adenoma surveillance and patients with irritable bowel symptoms had similar NNE compared with average-risk subjects. CONCLUSIONS: The prevalence of a colon lesion >9 mm varies on the basis of age, gender, race, and procedure indication. Understanding utilization and outcomes can lead to more optimal use of colonoscopy.