Shortage of Albendazole and Its Consequences for Patients with Cystic Echinococcosis Treated at a Referral Center in Italy

Albendazole (ABZ) is the best drug available to treat cystic echinococcosis (CE), a neglected tropical disease. Cystic echinococcosis patients often receive a continuous course of the drug for 6-12 months. In Italy, ABZ shortages occur almost on a yearly basis. We searched clinical records at the World Health Organization Collaborating Center for the Clinical Management of CE in Pavia, Italy, to estimate the amount of ABZ prescribed to patients between January 2012 and February 2017. The cost of ABZ was estimated at €2.25 per tablet based on the current market price in Italy. Patients to whom ABZ had been prescribed were contacted to determine if they had experienced difficulties in purchasing the drug and to assess how such problems affected their treatment. Of 348 identified CE patients, 127 (36.5%) were treated with ABZ for a total of 20,576 days. This led to an estimated cost of €92,592. Seventy-five patients were available for follow-up, 42 (56%) reported difficulties in obtaining ABZ. Of these patients, four (9.5%) had to search out of their region and 10 (23.8%) had to go out of the country. A total of 27 patients (64%) had to visit more than five pharmacies to locate the drug and 10 patients (23.8%) interrupted treatment because of ABZ nonavailability. Shortages in ABZ distribution can disrupt CE treatment schedules and jeopardize patient health

Augmenter of liver regeneration enhances the success rate of fetal pancreas transplantation in rodents

Background. Treatment of fetal pancreas (FP) isografts with insulin- like growth factor-I greatly improves the rate of conversion to euglycemia in diabetic rats. Complete knowledge of other factors that may facilitate the engraftment and function of FP in vivo is still embryonic. Augmenter of liver regeneration (ALR) is a newly described polypeptide growth factor found in weanling rat livers. ALR has trophic effects on regenerating liver. We studied the effects of in situ administration of this agent on FP isografts in rats. Methods. Streptozotocin-diabetic Lewis rats (blood glucose >300 mg/dl) received 16 FP isografts transplanted intramuscularly. ALR was delivered from day 1 through day 14, in doses of 40 or 400 ng/kg/d. Animals were followed for 3 months with serial weights and blood glucose monitoring. These animals were compared with those treated with vehicle alone. Results. Of the group treated with ALR at 40 ng/kg/day for 14 days, 89% (eight of nine) were euglycemic (P=0.0003). Of the group treated with ALR at 400 ng/kg/day for 14 days, 88% (seven of eight) were euglycemic (P=0.0007). Of the group treated with vehicle alone, none of the six were euglycemic. Euglycemia is defined here as glucose<200 mg/dl for 3 days. Pathology of the intramuscular transplant site showed patches of islet tissue embedded in fat. These patches demonstrated insulin immunoreactivity. Conclusions. Diabetes was reversed in a significantly greater proportion of FP + ALR-treated recipients than those animals treated with vehicle alone. Local delivery of growth factors my be used as an adjunct to FP transplantation to improve the rate of success. This in situ model may be useful to further evaluate other soluble factors

Pancreatic nodule positive for 68-Ga-DOTAPEPTIDE-PET: NET or ectopic spleen? The importance of a good differential diagnosis

Abstract Background Accessory spleen is a congenital defect in which splenic tissue is present outside the spleen. In 20% of cases, accessory spleen is localized within the pancreatic tail, a condition known as IPAS. The identification of this benign anomaly, which affects about 2% of general population, is not easy because it is often mistaken for a pNET which is more common, at around 5%. A 68-Ga-DOTAPEPTIDE-PET normally identifies pNETs with high rate of sensitivity and specificity, but in some conditions, it produces false positives, including IPAS. Materials and tools A clinical case we recently encountered, prompted us to review the available medical literature on the topic. Typing "intrapancreatic accessory spleen" into PubMed database and limiting research to the last 10 years yielded 121 results from which we selected the most relevant articles for decision-making, with a brief explanation of the reasons for selecting those. Our analysis focused on the most critical and least descriptive articles, those which clearly indicated the importance of differential diagnosis by promoting the use of advanced investigations in case of pancreatic nodule suspected for IPAS. Ultimately, our objective was to update the available guidelines recommendations. Discussion and conclusions Despite concern in the medical literature, a differential IPAS diagnosis is still subordinate to other clinical, radiological, nuclear medicine, and cytological criteria. After reviewing the literature, we recommend that IPAS should always be considered as a possibility before diagnosis of pNET is made. IPAS should be suspected in the presence of the following findings: asymptomatic pancreatic nodule found incidentally, absence of laboratory findings of NETs, localization in the pancreatic tail, between 1 and 3 cm in size with well-defined margins, homogeneous enhancement, and similar attenuation to the spleen on CT and MRI. In these cases, the use of advanced investigations beyond 68-Ga-DOTAPEPTIDE-PET must be systematic. The recognition of IPAS is not only a diagnostic refinement, but it also avoids unnecessary surgery for the patient

Phase- and Stage-Related Proportions of T Cells Bearing the Transcription Factor FOXP3 Infiltrate Primary Melanoma

Although tumor-infiltrating lymphocytes (TILs) of primary cutaneous melanoma (PCM) include cytolytic T cells able to exert anti-PCM immunity, progression of PCM most frequently occurs, raising the hypothesis that the PCM microenvironment may also exert suppressive forces, for example, possibly developed by regulatory T (TREG) lymphocytes. The aim of this study was to investigate whether TILs of PCMs include lymphocytes bearing the transcription factor forkhead box protein P3 (FOXP3), which is the TREG lineage specification molecule in mice, and is debated to have a similar role in humans. Fourteen patients with PCM were selected, of which four had radial growth phase (RGP) stage I melanoma, five had vertical growth phase (VGP) stage I melanoma, and five had VGP stage III–IV melanoma. Formalin-fixed, paraffin-embedded sections were utilized for immunohistochemical single and double stainings. TILs of PCMs included FOXP3-bearing lymphocytes, which predominantly were CD20- and CD8-negative, but CD3-, CD4-, and CD25-positive, thus consistent with the standard immunophenotypical characteristics of “natural” TREG cells. Further, the proportions of FOXP3-bearing lymphocytes were higher in vertical than in RGP (P=0.001), as well as in late than in early melanoma stages (P<0.001). Should these FOXP3-bearing lymphocytes actually exert regulatory capabilities within the PCM microenvironment, they may suppress “in vivo” the local anti-PCM immune response, thus favoring melanoma progression

The challenge of extraabdominal desmoid tumour management in patients with Gardner’s syndrome: radiofrequency ablation, a promising option

Desmoid tumours are benign, myofibroblastic stromal neoplasms common in Gardner's syndrome, which is a subtype of familial adenomatous polyposis characterized by colonic polyps, osteomas, thyroid cancer, epidermoid cysts, fibromas and sebaceous cysts. The primary treatment is surgery, followed by adjuvant radiotherapy, but the local recurrence rate is high, and wide resection can result in debilitating loss of function. We report the case of a 39-year-old man with Gardner's syndrome who had already undergone a total prophylactic colectomy. He developed desmoid tumours localized in the mesenteric root, abdominal wall and dorsal region, which were treated from 2003 through 2013 with several surgical procedures and percutaneous radiofrequency ablation. In 2008 and 2013, RFA was applied under ultrasonographic guidance to two desmoid tumours localized in the dorsal thoracic wall. The outcomes were low-grade pain and one case of superficial skin necrosis, but so far there has been no recurrence of desmoid tumours in these locations. Surgical resection remains the first-line therapy for patients with desmoid tumours, but wide resection may lead to a poor quality of life. Radiofrequency ablation is less invasive and expensive and is a possible therapeutic option for desmoid tumours in patients with Gardner's syndrome

Two-stage hepatectomy after autologous CD133+ stem cells administration: a case report

Extreme liver resection can provide a safer option and a chance of cure to otherwise unresectable patients when liver regeneration is boosted by PVE and stem cell administratio

Cytotoxic activity of a plant extract on cancer cells

Chemoprevention by natural products may be considered a promising approach to cancer control and management [1]. Many studies have demonstrated antiproliferative, cytostatic and cytotoxic activities of phytochemicals against cancer cells [2]. In this study, a plant extract from Arctium lappa, Berberis vulgaris and Eschscholtia californica was tested as potential anticancer agent. The antitumoral activity of this plant extract was tested on four human cancer cell lines: MCF-7 (breast carcinoma cells), Huh-7 (hepatic carcinoma cells), HTB-43 (oropharyngeal carcinoma cells) and ECV- 304 (urinary bladder carcinoma cells). The efficacy of the extract was compared to the common chemotherapeutic agent cyclophosphamide. Three plant extract concentrations were tested: 800, 650 and 450 ng/ml; for cyclophosphamide, three concentrations were assayed, according to literature data: 1300, 1000 and 850 ng/ml [3]. In addition, plant extract and cyclophosphamide were tested on two primary cell lines as controls, human gingival fibroblasts and human mammary fibroblasts. Cell viability was evaluated by the MTT [(3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, Sigma] colorimetric assay and the new xCELLigence system (Roche) for real-time monitoring of cell viability. All concentrations of plant extract exhibited a high level of cytotoxicity on MCF-7, Huh-7, HTB-43 and ECV-304 cancer cells, similar to cyclophosphamide, though they slightly reduced viability of human gingival and mammary fibroblasts. Conversely, the conventional chemotherapeutic drug showed a marked cytotoxicity on control cells. The potential of the plant extract has been demonstrated in vitro on various types of cancers, suggesting a possible use of this natural product as a promising anticancer agent. Further studies are needed to ascertain its efficacy in vivo and to elucidate its mechanism(s) of action at molecular and biochemical levels

Cytogenetic markers, DNA single-strand breaks, urinary metabolites, and DNA repair rates in styrene-exposed lamination workers.

The effect of occupational exposure to styrene on frequencies of chromosomal aberrations and binucleated cells with micronuclei and on single-strand break levels in peripheral blood lymphocytes was studied in 86 reinforced plastic workers and 42 control individuals (including 16 maintenance workers with intermittent, low-dose exposure). In these individuals, the irradiation-specific DNA repair rates and the repair rates of 8-oxoguanines were investigated. We assessed the exposure by measuring the concentrations of styrene in air and in blood and of mandelic acid, phenylglyoxylic acid, 4-vinyl phenol conjugates and regioisomeric phenyl hydroxyethyl mercapturic acids in urine. All these parameters correlated with one another. No clear relationship was found between the styrene exposure and the frequencies of chromosomal aberrations. Binucleated cells with micronuclei were moderately related to the parameters of styrene exposure. We found a negative correlation between all exposure parameters and single-strand breaks. The positive correlation between exposure parameters and DNA repair rates suggests that particular DNA repair pathways may be induced by styrene exposure

Prediction of morbidity and mortality after early cholecystectomy for acute calculous cholecystitis : results of the SPRi.MACC study

Peer reviewe

CryoSat Ice Baseline-D validation and evolutions

The ESA Earth Explorer CryoSat-2 was launched on 8 April 2010 to monitor the precise changes in the thickness of terrestrial ice sheets and marine floating ice. To do that, CryoSat orbits the planet at an altitude of around 720 km with a retrograde orbit inclination of 92∘ and a quasi repeat cycle of 369 d (30 d subcycle). To reach the mission goals, the CryoSat products have to meet the highest quality standards to date, achieved through continual improvements of the operational processing chains. The new CryoSat Ice Baseline-D, in operation since 27 May 2019, represents a major processor upgrade with respect to the previous Ice Baseline-C. Over land ice the new Baseline-D provides better results with respect to the previous baseline when comparing the data to a reference elevation model over the Austfonna ice cap region, improving the ascending and descending crossover statistics from 1.9 to 0.1 m. The improved processing of the star tracker measurements implemented in Baseline-D has led to a reduction in the standard deviation of the point-to-point comparison with the previous star tracker processing method implemented in Baseline-C from 3.8 to 3.7 m. Over sea ice, Baseline-D improves the quality of the retrieved heights inside and at the boundaries of the synthetic aperture radar interferometric (SARIn or SIN) acquisition mask, removing the negative freeboard pattern which is beneficial not only for freeboard retrieval but also for any application that exploits the phase information from SARIn Level 1B (L1B) products. In addition, scatter comparisons with the Beaufort Gyre Exploration Project (BGEP; https://www.whoi.edu/beaufortgyre, last access: October 2019) and Operation IceBridge (OIB; Kurtz et al., 2013) in situ measurements confirm the improvements in the Baseline-D freeboard product quality. Relative to OIB, the Baseline-D freeboard mean bias is reduced by about 8 cm, which roughly corresponds to a 60 % decrease with respect to Baseline-C. The BGEP data indicate a similar tendency with a mean draft bias lowered from 0.85 to −0.14 m. For the two in situ datasets, the root mean square deviation (RMSD) is also well reduced from 14 to 11 cm for OIB and by a factor of 2 for the BGEP. Observations over inland waters show a slight increase in the percentage of good observations in Baseline-D, generally around 5 %–10 % for most lakes. This paper provides an overview of the new Level 1 and Level 2 (L2) CryoSat Ice Baseline-D evolutions and related data quality assessment, based on results obtained from analyzing the 6-month Baseline-D test dataset released to CryoSat expert users prior to the final transfer to operations