Pancreatic intraepithelial neoplasia in association with intraductal papillary mucinous neoplasms of the pancreas: implications for disease progression and recurrence

The development of pancreatic cancer (PC) several years after curative resection for noninvasive intraductal papillary mucinous neoplasm (IPMN) and the presence of PC distant from IPMN suggest that PC may develop independently of the IPMN. Here, we identified pancreatic intraepithelial neoplasia (PanIN) lesions, the putative precursors of PC, in the ducts of pancreata resected for IPMN and assessed the frequency of molecular aberrations common to PanIN and PC, within these lesions. The protein expression of p53, p21(WAF1/CIP1), cyclin D1, p16(INK4A) and DPC4/Smad4 were examined by immunohistochemistry in 267 PanIN lesions from a cohort of 23 patients with IPMN. Overexpression of p21(WAF1/CIP1) was present in PanIN-1A and -1B lesions and increased in frequency in PanIN-2 and PanIN-3. Overexpression of p53 and cyclin D1, and loss of p16(INK4A) expression were detected in PanIN-2 and PanIN-3 lesions. Loss of DPC4/Smad4 expression occurred only in the PanIN-3 lesions. PanIN lesions that were more dysplastic than the coincident IPMN were identified in 5 of 12 patients, and 2 of these contained a greater number of aberrations in protein expression than the IPMN. PanIN lesions seen in association with IPMN demonstrate molecular and histologic changes identical to PanIN lesions found in association with PC and, in some cases, are more advanced than the associated IPMN. These data suggest that PanIN lesions found in the ducts of a pancreas with IPMN may be relevant to the development of PC either coincident with IPMN or in the remnant pancreas after curative resection of IPMN.     

锌酞菁脂质体光动力作用引起小鼠肿瘤的细胞程序性死亡

电镜观察了锌酞菁脂质体光动力作用引起小鼠ＭＳ－２纤维肉瘤的形态学变化。发现其作用很强，并对肿瘤细胞有明显的直接影响。肿瘤细胞的结构表现出明显的程序性细胞死亡（ａｐｏｐｔｏｓｉｓ，ｐｒｏｇｒａｍｍｅｄｃｅｌｄｅａｔｈ）的特点：胞核染色质凝聚边集、核固缩、核破裂、染色质凝块流失、胞质内吞噬现象、胞膜表面肿胀粗钝的胞突形成、细胞碎裂等。加深了对锌酞菁脂质体光敏作用机理的认识，但其详细的发生机制和调节途径有待阐明。     

Modulation of in vitro eosinophil progenitors by hydrocortisone: role of accessory cells and interleukins

The growth of human eosinophil progenitors (CFU-Eo) and the modulation of growth by hydrocortisone were studied as functions of the presence of lymphocytes and monocytes in marrow cells under study; and the source of colony-stimulating factors, specifically, media conditioned by macrophage-like cell line, GCT; phytohemagglutinin-stimulated mononuclear cells (PHA-LCM); or the T cell line, MO. CFU-Eo growth was greatest in marrow containing accessory cells as compared to marrow depleted of accessory cells; and in marrow treated with phytohemagglutinin-stimulated leukocyte conditioned media (PHA-LCM) or MO (T cell line)-conditioned medium (MO-CM) as compared with GCT cell- conditioned medium (GCT-CM). Hydrocortisone reproducibly inhibited eosinophil progenitor growth in unfractionated marrow stimulated by GCT- CM. This effect was abrogated by admixing irradiated mononuclear cells or T lymphocytes with the target marrow or by adding interleukin 1 or interleukin 2 (IL-1, IL-2). Inhibition by hydrocortisone did not occur when monocyte and T lymphocyte depleted marrow was studied. Unlike GCT- CM, MO-CM and PHA-LCM stimulated equal proportions of eosinophil progenitors in nondepleted and accessory cell-depleted marrow and demonstrated less hydrocortisone inhibition. However, both GCT-CM and PHA-LCM produced in the presence of hydrocortisone stimulated significantly fewer CFU-Eos in both unfractionated and accessory cell- depleted marrow target populations. These results indicate that the growth of CFU-Eo and inhibition of growth by hydrocortisone is a direct function of a monocyte-T cell interaction and probably is mediated through effects on the production/release of eosinophil colony stimulating factor (Eo-CSF).     

Antiobesity effects of etiocholanolones in diabetes (db), viable yellow (Avy), and normal mice

Two metabolites of the adrenal steroid dehydroepiandrosterone (DHEA), 3 alpha-hydroxyetiocholanolone and 3 beta-hydroxyetiocholanolone, were found to have antiobesity properties with respect to both prevention of the development of obesity as well as weight reduction after obesity was established. All of the obesity types studied responded to metabolite therapy to a greater or lesser extent. The more natural obesity seen in certain strains of mice with aging responded most rapidly to the feeding of either metabolite. The effective dosage (0.1%) fed in the diet was only one quarter the dosage required for DHEA to produce the same effect in preventing diabetes symptoms in C57BL/Ks diabetic (db) mutant mice. Unlike DHEA, neither metabolite produced any undesirable estrogenic or androgenic side-effects. 3 alpha-hydroxyethiocholanolone and 3 beta-hydroxyetiocholanolone, formerly considered only as inert end products of steroid metabolism, have beneficial actions in mice with various diabetes-obesity conditions and may be metabolic effectors in their own right.     

Chemical and biologic characterization of a lipopolysaccharide extracted from the Lyme disease spirochete (Borrelia burgdorferi)

A lipopolysaccharide (LPS) was isolated from the Lyme disease spirochete by a modification of the hot phenol-water method. The material was composed of 45% carbohydrate, 8% protein, 44% lipid A, and 1% 3-deoxy-D-mannooctulosonic acid and accounted for approximately 1.5% of the cellular dry weight. The isolated LPS possessed several biologic activities characteristic of endotoxins. The LPS was pyrogenic for rabbits, mitogenic for human mononuclear cells and murine splenocytes, capable of clotting limulus lysate, and cytotoxic for murine macrophages. LPS extracted from Borrelia burgdorferi by the petroleum-ether:chloroform:liquid-phenol procedure was also characterized. The results show that the Lyme disease spirochete contains a hitherto unknown LPS that is biologically active in vitro, and the expression of such activities in vivo may play an important role in the pathogenesis of Lyme disease. Some of the clinical manifestations of other spirochetal disease may be explained by similar endotoxins in those organisms. To our knowledge this is the first report of an LPS extracted from a spirochete that is known to be a human pathogen.     

Single port laparoscopic right colonic resection using a 'vessel-first' approach

Aim Single port laparoscopic colorectal surgery (SPLC), performed through a single incision of ≤ 3 cm, has been shown to be feasible. This study aimed to assess its safety and efficacy when used as the method of choice for right hemicolectomy. Method A prospective study was carried out of patients undergoing right hemicolectomy using a single port laparoscopic technique. They were compared with a historical series of patients undergoing right hemicolectomy using a multiport laparoscopic technique. Between December 2009 and September 2010, single port surgery replaced conventional laparoscopic colorectal surgery (LCS) for radical medial to lateral right hemicolectomy performed by a single surgeon. Histology, length of hospital stay, complications, conversions and readmissions were recorded. Results Fourteen patients were treated using single port laparoscopic surgery (SPLC): 10 for carcinoma (Dukes A1, B6, C3) and four for Crohn’s disease. Twelve patients were treated using multiport laparoscopic colorectal surgery (LCS): eight for carcinoma (Dukes B4, C3, Carcinoid 1), three for Crohn’s disease and one for adenoma. The median (interquartile range) operative time for the SPLC group was 120 (90–135) min and for the LCS group was 135 (116–150) min. The median (interquartile range) length of hospital stay was 3.5 (2.0–5.0) days for the SPLC group and for the LCS group was 4.0 (3.8–7.0) days. The median (interquartile range) number of lymph nodes removed for SPLC patients was 14.5 (9.8–19.5) and for the LCS patients was 14.5 (13.0–19.5). There were no conversions, no complications and no readmissions in either group. Conclusion These data confirm the feasibility of the technique. Furthermore they suggest that it is safe and efficacious.     

Relationship between deep vein thrombosis and pulmonary embolism following THA and TKA

Patients undergoing total hip arthroplasty (THA) and total knee arthroplasty (TKA) are at risk for venous thromboembolisms, including deep vein thrombosis and pulmonary embolism. Most deep vein thromboses are asymptomatic, but they can lead to long-term morbidity to the same extent as symptomatic events. The risk of complications of venous thromboembolisms depends on the location of thrombi; potential long-term complications include recurrent venous thromboembolism, postthrombotic syndrome, and chronic thromboembolic pulmonary hypertension. Risk of recurrence persists for several years after the initial event. Approximately 20% of recurrent events are pulmonary embolisms, and approximately half of those are fatal. The causal relationship between deep vein thrombosis and pulmonary embolism remains controversial. Some consider them distinct clinical entities, while others have found asymptomatic distal deep vein thrombosis to be associated with elevated risk of developing pulmonary embolism. Unique coagulation factors may be associated with orthopedic surgery patients that differentiate them from patients undergoing other types of surgery. Symptomatic and asymptomatic deep vein thrombosis can lead to the development of recurrent venous thromboembolism, pulmonary embolism, postthrombotic syndrome, and chronic thromboembolic pulmonary hypertension, all of which are associated with reduced quality of life and increased health care expenditures. Thromboprophylaxis is therefore important in patients undergoing THA or TKA. However, traditional anticoagulants are not ideal, particularly for long-term use. Orthopedic surgeons should be aware of the causes and potential sequelae of venous thromboembolism and of the new thromboprophylactic agents that can help prevent it.     

Clinical experience with alpha-particle emitting 211At: treatment of recurrent brain tumor patients with 211At-labeled chimeric antitenascin monoclonal antibody 81C6.

alpha-Particle-emitting radionuclides, such as (211)At, with a 7.2-h half-life, may be optimally suited for the molecularly targeted radiotherapy of strategically sensitive tumor sites, such as those in the central nervous system. Because of the much shorter range and more potent cytotoxicity of alpha-particles than of beta-particles, (211)At-labeled agents may be ideal for the eradication of tumor cells remaining after surgical debulking of malignant brain tumors. The main goal of this study was to investigate the feasibility and safety of this approach in patients with recurrent malignant brain tumors. METHODS: Chimeric antitenascin monoclonal antibody 81C6 (ch81C6) (10 mg) was labeled with 71-347 MBq of (211)At by use of N-succinimidyl 3-[(211)At]astatobenzoate. Eighteen patients were treated with (211)At-labeled ch81C6 ((211)At-ch81C6) administered into a surgically created resection cavity (SCRC) and then with salvage chemotherapy. Serial gamma-camera imaging and blood sampling over 24 h were performed. RESULTS: A total of 96.7% +/- 3.6% (mean +/- SD) of (211)At decays occurred in the SCRC, and the mean blood-pool percentage injected dose was < or = 0.3. No patient experienced dose-limiting toxicity, and the maximum tolerated dose was not identified. Six patients experienced grade 2 neurotoxicity within 6 wk of (211)At-ch81C6 administration; this neurotoxicity resolved fully in all but 1 patient. No toxicities of grade 3 or higher were attributable to the treatment. No patient required repeat surgery for radionecrosis. The median survival times for all patients, those with glioblastoma multiforme, and those with anaplastic astrocytoma or oligodendroglioma were 54, 52, and 116 wk, respectively. CONCLUSION: This study provides proof of concept for regional targeted radiotherapy with (211)At-labeled molecules in oncology. Specifically, the regional administration of (211)At-ch81C6 is feasible, safe, and associated with a promising antitumor benefit in patients with malignant central nervous system tumors.     

Validity and reliability of the Ergomopro powermeter

The aim of this investigation was to assess the validity and reliability of the Ergomopro powermeter. Nine participants completed trials on a Monark ergometer fitted with Ergomopro and SRM powermeters simultaneously recording power output. Each participant completed multiple trials at power outputs ranging from 50 to 450 W. The work stages recorded were 60 s in duration and were repeated three times. Participants also completed a single trial on a cycle ergometer designed to assess bilateral contributions to work output (Lode Excaliber Sport PFM). The power output during the trials was significantly different between all three systems, (p < 0.01) 231.2 +/- 114.2 W, 233.0 +/- 112.4 W, 227.8 +/- 108.8 W for the Monark, SRM and Ergomopro system, respectively. When the bilateral contributions were factored into the analysis, there were no significant differences between the powermeters (p = 0.58). The reliability of the Ergomopro system (CV%) was 2.31 % (95 % CI 2.13 - 2.52 %) compared to 1.59 % (95 % CI 1.47 to 1.74 %) for the Monark, and 1.37 % (95 % CI 1.26 - 1.50 %) for the SRM powermeter. These results indicate that the Ergomopro system has acceptable accuracy under these conditions. However, based on the reliability data, the increased variability of the Ergomopro system and bilateral balance issues have to be considered when using this device.