Changing the pathophysiology of solid tumours: the potential of TNF and other vasoactive agents.

Solid tumour therapy with chemotherapeutic drugs is hampered by a number of factors resulting in poor results and failure of initially promising drugs. From the application of Tumour Necrosis Factor alpha in the melphalan-based Isolated Limb perfusion some lessons could be learned. Most importantly, combination of treatment approaches, certainly when multiple targets are involved, increases the effectiveness of the therapy. Clinical outcome may improve dramatically when the tumour pathophysiology is changed in such a way that co-administered chemotherapeutics are more active or are capable of reaching the tumour cells better. Here some of the methodologies and drug combinations which improve solid tumour therapy through acting on the tumour pathophysiology are discussed.     

Quantitative assessment of the stent/scaffold strut embedment analysis by optical coherence tomography

The degree of stent/scaffold embedment could be a surrogate parameter of the vessel wall-stent/scaffold interaction and could have biological implications in the vascular response. We have developed a new specific software for the quantitative evaluation of embedment of struts by optical coherence tomography (OCT). In the present study, we described the algorithm of the embedment analysis and its reproducibility. The degree of embedment was evaluated as the ratio of the embedded part versus the whole strut height and subdivided into quartiles. The agreement and the inter- and intra-observer reproducibility were evaluated using the kappa and the interclass correlation coefficient (ICC). A total of 4 pullbacks of OCT images in 4 randomly selected coronary lesions with 3.0 × 18 mm devices [2 lesions with Absorb BVS and 2 lesions with XIENCE (both from Abbott Vascular, Santa Clara, CA, USA)] from Absorb Japan trial were evaluated by two investigators with QCU-CMS software version 4.69 (Leiden University Medical Center, Leiden, The Netherlands). Finally, 1481 polymeric struts in 174 cross-sections and 1415 metallic struts in 161 cross-sections were analyzed. Inter- and intra-observer reproducibility of quantitative measurements of embedment ratio and categorical assessment of embedment in Absorb BVS and XIENCE had excellent agreement with ICC ranging from 0.958 to 0.999 and kappa ranging from 0.850 to 0.980. The newly developed embedment software showed excellent reproducibility. Computer-assisted embedment analysis could be a feasible tool to assess the strut penetration into the vessel wall that could be a surrogate of acute injury caused by implantation of devices.     

Change in neoadjuvant chemotherapy could alter the prognosis of patients with pancreatic adenocarcinoma: A case report

BACKGROUNDNeoadjuvant treatment has become a standard of care for borderline or locally advanced pancreatic cancer and is increasingly considered even for up-front resectable disease. The aim of this article is to present the case of a 62-year-old patient with locally advanced pancreatic adenocarcinoma who was successfully treated with gemcitabine plus nab-paclitaxel after the failure of the first line treatment.CASE SUMMARYComputerized tomography scan and magnetic resonance imaging demonstrated a nodular lesion of ill-defined limits in the body of the pancreas, measuring approximately 4.2 cm × 2.7 cm, with an infiltrative aspect. The tumor had contact with the superior mesenteric vein, splenomesenteric junction and the proximal segment of the splenic artery, causing focal reduction of its lumens. Due to vascular involvement, neoadjuvant chemotherapy treatment with eight cycles of “folinic acid, 5-fluorouracil, irinotecan and oxaliplatine” (FOLFIRINOX) were performed. At the end of the cycles, surgery was performed, but the procedure was interrupted due to finding of lesions suspected of metastasis. Gemcitabine plus nab-paclitaxel was then successfully used for neoadjuvant treatment with subsequent R0 surgical resection.CONCLUSIONGemcitabine plus nab-paclitaxel may be effective as an alternative regimen when FOLFIRINOX fails as the first line of treatment, suggesting the need for further studies to identify which patients would benefit from each type of therapeutic approach.     

Detection of antibodies to Trypanosoma cruzi among blood donors in the southwestern and western United States. II. Evaluation of a supplemental enzyme immunoassay and radioimmunoprecipitation assay for confirmation of seroreactivity

BACKGROUND: Chagas' disease, caused by the protozoan parasite Trypanosoma cruzi, is endemic to Latin America and may be transmitted in the United States via blood donated by infected immigrants. Blood- borne pathogens such as T. cruzi require supplemental testing for confirmation of seroreactivity. STUDY DESIGN AND METHODS: A study was undertaken to determine an optimal scheme for confirmation of seroreactivity in repeatedly reactive samples identified by the Chagas antibody enzyme immunoassay (EIA). The procedure for initial confirmation involves three purified antigens coated onto three separate polystyrene beads and uses an EIA format. If the sample is reactive with two of three or three of three antigens, it is confirmed as seroreactive. If none or one of three beads is reactive, the sample is indeterminate and subjected to a radioimmunoprecipitation assay (RIPA). The RIPA must demonstrate characteristic bands at 32, 34, and 90 kDa. RESULTS: When tested with sera from persons with potentially cross-reactive diseases (n = 39) or against a presumed negative population from southeast Wisconsin (n = 289), the confirmatory EIA had a specificity of 100 percent. Sensitivity was 100 percent (28/28) with xenodiagnosis-positive sera and 97.6 percent (80/82) with chagasic sera from Latin America. The RIPA showed a specificity of 100 percent in EIA- nonreactive samples (n = 100) and a sensitivity of 100 percent with both xenodiagnosis-positive (28/28) and chagasic (82/82) sera. CONCLUSION: The confirmatory EIA and the RIPA together provide a highly specific and sensitive means of confirming seroreactivity for antibodies to T. cruzi.     

Yersinia-related Arthritis in the United Kingdom. A Report of 12 Cases and review of the Literature

Reactive arthritis following infection with Yersinia is endemicin Scandanavian countries; the prevalence is low in the UK,however. We have reviewed the literature pertaining to Yersinia-relatedreactive arthritis in the UK and describe 12 patients who presentedover a 3-year period with an asymmetrical seronegative polyarthropathyand serological evidence of recent Yersinia infection. Fivepatients recalled having a diarrhoeal illness prior to the onsetof the arthropathy. None had a prior history of psoriasis, inflammatorybowel disease or ankylosing spondylitis. A history of urethraldischarge was elicited from one patient. Extra-articular manifestationswere seen in three patients (iritis in two, erythema nodosumin another). Four patients developed chronic joint disease afterperiods of 4, 6, 8, and 18 months, respectively. The prevalenceof Yersinia-related arthritis in the UK may be higher than previouslythought.     

Prognosis in patients with sentinel node-positive melanoma without immediate completion lymph node dissection

BACKGROUND: The therapeutic value of immediate completion lymph node dissection (CLND) for sentinel node (SN)-positive melanoma is unknown. The aim of this study was to evaluate the impact of immediate CLND on the outcome of patients with SN-positive melanoma. METHODS: Patients with SN metastases treated between 1993 and 2008 at ten cancer centres from the European Organization for Research and Treatment of Cancer Melanoma Group were included in this retrospective study. Maximum tumour size, intranodal location and penetrative depth of SN metastases were measured. Outcome in those who had CLND was compared with that in patients who did not undergo completion lymphadenectomy. RESULTS: Of 1174 patients with SN-positive melanoma, 1113 (94·8 per cent) underwent CLND and 61 (5·2 per cent) did not. Median follow-up for the two groups was 34 and 48 months respectively. In univariable survival analysis, CLND did not significantly influence disease-specific survival (hazard ratio (HR) 0·89, 95 per cent confidence interval 0·58 to 1·37; P = 0·600). However, patients who did not undergo CLND had more favourable prognostic factors. Matched-pair analysis, with matching for age, Breslow thickness, tumour ulceration and SN tumour burden, showed that CLND had no influence on survival (HR 0·86, 0·46 to 1·61; P = 0·640). After adjusting for prognostic factors in multivariable survival analyses, no difference in survival was found. CONCLUSION: In these two cohorts of patients with SN-positive melanoma and prognostic heterogeneity, outcome was not influenced by CLND. Copyright ? 2012 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd.     

Advancement of multiple myeloma from diagnosis through plateau phase to progression does not involve a new B-cell clone: evidence from the Ig heavy chain gene

The Ig heavy chain (IgH) gene was used as a marker to investigate clonal succession and the origin of the neoplastic cell in multiple myeloma. The polymerase chain reaction (PCR) was used to amplify a section of the rearranged IgH gene at diagnosis and at progression in 21 patients who had exhibited a plateau phase. A monoclonal PCR product was seen for 16 of the patients and the product present at progression was of the same molecular weight as that at diagnosis. This finding suggests that the IgH rearrangement present at diagnosis and progression was the same. This was confirmed by sequencing the IgH gene in 10 patients. The IgH genes were found to be hypermutated at diagnosis, but no further hypermutation occurred during the course of the disease. The results provide evidence that the neoplastic cell in myeloma may originate as a memory B cell, plasmablast, or plasma cell, and suggest that progression beyond the plateau phase is not caused by clonal succession.     

Acceptance of self-testing for increased vaginal pH in different subsets of Ugandan women

We assessed the acceptance of self-testing for vaginal pH in 344 Ugandan women in different clinical settings. Women tested themselves by insertion of a gloved finger into the vagina to test vaginal pH and provide a smear on a glass slide. None of the tested women found the test very difficult: 8% found it somewhat difficult, 16% rather easy and 76% very easy to do. Of the 20% who found it difficult to read the test result, more women were attending a family planning clinic or had a higher diploma (P = 0.001). Pregnant women were least likely to understand of the meaning of the test, while those visiting family planning clinics had the opposite experience. HIV-infected women were most motivated to accept: 95% would be happy to use the test more often if requested, and another 3.5% felt they might be better motivated to do repeat testing after extra explanation. Self-sampling of vaginal pH is well accepted by Ugandan women. Our new method also allows diagnostic work-up by formal microscopy. Before commencing large-scale population screening, unexpected reactions of different subpopulations should be taken into account.     

WONCA研究论文摘要汇编——基层抑郁症风险患者的连续性服务

背景目前已开展了对重性精神病患者进提供连续性服务的研究。目的探讨基层对有抑郁症风险患者提供连续性服务的水平,并与对心力衰竭患者的服务水平进行对比。方法采用抑郁症风险患者与心力衰竭患者对比的探索性研究。采用患者问卷评估服务的持续性,包含如下内容:(1)联系的服务提供者数(个人连续性);(2)诊所内服务提供者之间的合作(团队连续性)(6个项目,分数1~5分);(3)诊所外全科医师与服务提供者之间的合作(跨界连续性)(4个项目,分数1~5分)。结果大多数抑郁症风险患者在过去1年中寻遍整个服务提供界联系了几个服务提供者,曾遇到过高水平团队连续性服务及低水平跨界连续性服务。在诊所中可接触到的不同服务提供者要明显多于心力衰竭患者服务提供者(P<0.01)。抑郁症风险患者的服务提供者之间的合作更好一些,每项平均得分4.3分,心力衰竭患者得分为4.0分(P=0.03)。然而,跨界连续性服务方面正好相反:抑郁症风险患者每项平均得分3.5分,心力衰竭患者得分为4.0分(P=0.01)。结论抑郁症风险患者与心力衰竭患者之间的探索性对比显示:体验服务连续性方面的差距不大。对此还应行进一步分析。