Conventional Versus Traction-Assisted Endoscopic Submucosal Dissection for Esophageal, Gastric, and Colorectal Neoplasms: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Endoscopic submucosal dissection (ESD) is increasingly being utilized for the resection of superficial gastrointestinal neoplasms. However, the long procedure time poses a technical challenge for conventional ESD (C-ESD). Traction-assisted ESD (T-ESD) was developed to facilitate the procedure by reducing its duration. This study compares the efficacy and safety of C-ESD versus T-ESD in the treatment of esophageal, gastric, and colorectal neoplasms. Nine randomized controlled trials (RCTs) were analyzed. Traction-assisted ESD exhibited shorter mean dissection times for the esophagus and colorectal regions and lower perforation rates in colorectal cases. No significant differences were observed in en bloc resection or bleeding rates. Traction-assisted ESD proves to be more efficient in mean procedure time for esophageal and colorectal cases and safer in perforation rates for colorectal cases, but similar rates are noted for en bloc resection or bleeding.

Study protocol: understanding the pathophysiologic mechanisms underlying delirium in older people undergoing hip fracture surgery.

BACKGROUND: Postoperative delirium (POD) is a common complication of older people undergoing hip fracture surgery, which negatively affects clinical- and healthcare-related outcomes. Unfortunately, POD pathophysiology is still largely unknown, despite previous studies showing that neuroinflammation, neuroendocrine dysfunction, increased reactive oxidative stress (ROS), and endothelial dysfunctions may be involved. There is also evidence that many of the pathophysiological mechanisms which are involved in delirium are involved in sarcopenia too. This article describes the protocol of a pilot study to evaluate the feasibility of a larger one that will explore the pathophysiological mechanisms correlating POD with sarcopenia. We will analyse whether various biomarkers reflecting neuroinflammation, ROS, neuroendocrine disorders, and microvasculature lesions will be simultaneously expressed in in the blood, cerebrospinal fluid (CSF), and muscles of patients developing POD. METHODS: Two centres will be involved in this study, each recruiting a convenient sample of ten older patients with hip fracture. All of them will undergo a baseline Comprehensive Geriatric Assessment, which will be used to construct a Rockwood-based Frailty Index (FI). Blood samples will be collected for each patient on the day of surgery and 1 day before. Additionally, CSF and muscle fragments will be taken and given to a biologist for subsequent analyses. The presence of POD will be assessed in each patient every morning until hospital discharge using the 4AT. Delirium subtypes and severity will be assessed using the Delirium Motor Subtype Scale-4 and the Delirium-O-Meter, respectively. We will also evaluate the patient's functional status at discharge, using the Cumulated Ambulation Score. DISCUSSION: This study will be the first to correlate biomarkers of blood, CSF, and muscle in older patients with hip fracture.

Prescribing errors intercepted by pharmacist intervention in care of patients hospitalised with breast and gynaecological cancer at a Brazilian teaching hospital.

Oncologic inpatients often require multiple drug therapy. They may be at higher risk of experiencing prescribing errors, which pharmacist interventions may help to avoid. This study aimed to evaluate the types of prescribing errors, pharmaceutical interventions and differences in clinical significance, in prescriptions for hospitalised patients with breast and gynaecological cancer. A cross-sectional, prospective study was conducted at the oncology ward of a clinic specialised in breast and gynaecology cancer. A clinical pharmacist analysed prescriptions, identified errors, performed interventions and classified clinical significance. A total of 1,874 prescriptions of 248 patients were evaluated; 11.5% prescriptions were involved at least in one prescribing error, totalising 283 errors. The most common error was unsafe medication due to drug interaction (89[31.4%]). Drugs for the alimentary tract and metabolism, and nervous system were the most involved in errors with statistical association (p = .0246 and p = .0002 respectively). Of the 294 interventions, 73.5% were accepted. The clinical significance of prescribing errors and interventions were classified as significant and very significant respectively. The pharmacist interventions obtained a good acceptance rate and impact significantly, avoiding prescribing errors classified as significant.

Can polyacrylic acid treat sexual dysfunction in women with breast cancer receiving tamoxifen?

OBJECTIVE: There is a lack of safety data supporting the use of hormone therapy in women who have had breast cancer and who have complained of genitourinary syndrome of menopause (GSM). The objective was to test the efficacy of two non-hormonal therapies for vaginal dryness. METHODS: This was a randomized trial with 52 women with breast cancer who were being treated with tamoxifen and who complained of vaginal dryness. The volunteers answered two questionnaires to evaluate sexual function (Female Sexual Function Index, FSFI) and a customized GSM questionnaire. The women were randomized into two groups: 25 (48.1%) in the polyacrylic acid group and 27 (51.9%) in the lubricant group, using either one of the treatments for 30 days, and after they were invited to answer the questionnaires again. RESULTS: There was improvement in the FSFI after both treatments. The polyacrylic acid group showed a decrease in sexual dysfunction from 96% to 24% (p < 0.0001) and the lubricant group showed a decrease from 88.9% to 55.6% (p = 0.0027). CONCLUSIONS: The results of this study showed that both treatments improved sexual function; however, polyacrylic acid was superior to the lubricant in treating sexual dysfunction.

Plant-based active photoprotectants for sunscreens.

Excessive exposure to the sun's radiation is the major exogenous mediator of skin damage, which accelerates skin ageing and increases the risk of developing skin cancer. Compounds with photoprotectant activity are extremely useful for decreasing the effect of ultraviolet (UV) radiation on the skin; however, numerous sun filters, especially organic sunscreens, are allergenic. Therefore, the development of formulations containing plant extracts, which may be potentially safer, is extensively being explored. Plant-based cosmetics are commonly used to avoid skin ageing because they contain antioxidant agents that minimize free radical activity, and numerous studies have investigated the skin-protectant effects of related plant species. In addition to their antioxidant properties, plant-based cosmetics protect the skin against solar radiation because they contain polyphenols such as flavonoids and carotenoids. Therefore, this study aims to present a review of plant species commonly used in sunscreens to protect the skin against damage due to sunlight exposure.

Update on ultraviolet A and B radiation generated by the sun and artificial lamps and their effects on skin.

Solar radiation, especially ultraviolet A (UVA) and ultraviolet B (UVB), can cause damage to the human body, and exposure to the radiation may vary according to the geographical location, time of year and other factors. The effects of UVA and UVB radiation on organisms range from erythema formation, through tanning and reduced synthesis of macromolecules such as collagen and elastin, to carcinogenic DNA mutations. Some studies suggest that, in addition to the radiation emitted by the sun, artificial sources of radiation, such as commercial lamps, can also generate small amounts of UVA and UVB radiation. Depending on the source intensity and on the distance from the source, this radiation can be harmful to photosensitive individuals. In healthy subjects, the evidence on the danger of this radiation is still far from conclusive.

Impact of drug formulation and free platinum/cisplatin ratio on hypersensitivity reactions to cisplatin: formulation matters.

WHAT IS KNOWN AND OBJECTIVE: Use of cisplatin can induce type I hypersensitivity reactions that may also be linked to the quality of the drug utilized. We observed cases of hypersensitivity that appeared to be associated with the brand of cisplatin used. The aim of this study was to compare two different brands of cisplatin in relation to type I hypersensitivity reactions. METHODS: Brand A was used in a tertiary care teaching hospital until 2012, and use of brand B started from January 2013, when the first hypersensitivity cases were observed. Patients were categorized based on symptom. Cisplatin of both brands was analysed by high-performance liquid chromatography (HPLC) and high-resolution electrospray ionization mass spectrometry (ESI-(+)-MS) and characterized according to US Pharmacopeia. RESULTS AND DISCUSSION: There were no cases of hypersensitivity associated with the use of cisplatin brand A, whereas four of 127 outpatients that used cisplatin brand B were affected. The two brands were in accordance with the US Pharmacopeia parameters, and there was no significant difference in the total platinum levels between the two brands when analysed by HPLC. However, high-resolution ESI-(+)-MS analyses show that brand B contains approximately 2.7 times more hydrolysed cisplatin than brand A. WHAT IS NEW AND CONCLUSION: The increase in the hydrolysed form of cisplatin found in brand B may be the cause of the hypersensitivity reaction observed in a subset of patients. We present the first study of the quality of drugs by high-resolution ESI-(+)-MS. Drug regulatory agencies and manufacturers should consider including measurement of hydrolysed cisplatin as a quality criterion for cisplatin formulations.

Avaliação de potenciais interações medicamentosas em prescrições de pacientes internadas, em hospital público universitário especializado em saúde da mulher, em Campinas-SP / Potential drug interaction evaluation in medical prescriptions in a public hospital specialized in women care, in Campinas, SP

Interação medicamentosa (IM) é um evento clínico em que os efeitos de um fármaco são alterados pelo uso concomitante ou anterior à ingestão de outro fármaco, alimento ou bebida. O estudo teve como objetivo identificar IM em prescrições da Unidade de Terapia Intensiva (UTI) e do Alojamento Conjunto (AC). Foram avaliadas 36 prescrições da UTI e 274 do AC e as IM foram listadas como "maiores", "moderadas" e "menores", tendo por base o site Drugs.com. Na UTI, foram identificadas 105 interações maiores, 171 moderadas e 18 menores. Na AC, foram identificadas 64 interações maiores, 64 interações moderadas e 4 interações menores. Para as IM classificadas como "maiores", realizou-se estudo comparativo com a base DrugDex/Micromedex® e com o software OPharmacêutico®, constatando-se que a IM de metoclopramida com tramadol, que representava 63,16% das IM da UTI e 100% das IM do AC, não são classificadas como "maiores". A identificação de IM, de relevância clínica, e o seu monitoramento permitem tratamentos mais efetivos com o menor número possível de complicações causadas por IM, diminuindo o tempo de internação e, consequentemente, os custos do hospital.

Drug interaction (DI) is a common clinical occurrence, in which the effects of one drug are altered by the simultaneous or previous use of another drug, food or drink. The aim of this study was to identify DI in medical prescriptions issued in the intensive care unit (ICU) and common shelter (CS) at a public women?s hospital in Brazil. Thirty-six prescriptions from the ICU and 271 prescriptions from the CS were analyzed and the DIs classified as "major", "moderate" and "minor", based on the database at the website Drugs.com. At the ICU, 105 "major", 171 "moderate" and 18 "minor" DIs were identified, while at the CS, the numbers found were 64, 64 and 4, respectively. For major DIs, a comparative analysis was carried out with another database, DrugDex/MicromedexTM, and the program OPharmaceuticoTM, revealing a lack of standardization and conflicting information in the different databases. Pharmacosurveillance in the wards, carried out by a pharmacist to identify the clinically relevant DIs and monitor their clinical manifestations, would enable more effective treatments to be given, with the smallest possible number of complications due to DIs, thus reducing lengths of stay and hospital costs.

Breast cancer classification according to immunohistochemical markers: clinicopathologic features and short-term survival analysis in a population-based study from the South of Switzerland.

BACKGROUND: Breast cancer may be classified into distinct molecular subtypes based on gene expression profiling and/or immunophenotypic characteristics. Aim of the study was to investigate prevalence, clinicopathologic features and overall survival (OS) of molecular subtypes, in a large European population-based study. PATIENTS AND METHODS: All invasive breast cancers from 2003 to 2007 were selected from the files of Ticino Cancer Registry. Molecular subtypes were defined by immunohistochemical markers. Clinicopathological characteristics and short-term OS were analyzed. RESULTS: Of 1214 invasive breast cancers, 73.2% were luminal A subtype, 13.8% luminal B, 7.4% basal like and 5.6% Her2/neu. Basal like presented largely in premenopausal women and displayed aggressive features, such as large tumor size, poorly differentiated cancers, high Ki-67 proliferation index and the worst 24-month OS. Luminal A included the highest percentage of patients >70, the highest proportion of stage I tumors and well/moderately differentiated lesions. Her2/neu was more frequent in postmenopausal women and showed the highest percentage of positive lymph nodes and stage IV cases. CONCLUSION: This is a comprehensive European population-based study on breast cancer molecular subtypes. We provide strong evidence that the molecular classification is useful for clinical management and superior to World Health Organization classification in terms of short-term prognostic value.

Secondary outputs of alpha1-antitrypsin deficiency targeted detection programme.

Targeted detection programmes are recommended to identify subjects affected by severe alpha1-antitrypsin deficiency (AATD). Guidelines are available to address physicians towards subjects at high risk for AATD. We wanted to investigate the clinical characteristics of subjects enrolled in the programme, who result as not being affected by severe AATD; this information is not available in the present literature. We elaborated data contained in the questionnaires accompanying the samples of 2127 Italian subjects submitted for AATD detection in a period spanning 11 years (1996-2006). A total of 588 subjects were eligible to enter this study: PI*MM subjects and subjects with intermediate AATD, referred for lung disease, were characterised by a relatively young mean age, and a high proportion (31.2% and 28.6%, respectively) were never smokers. Fifty percent or more had symptoms of chronic bronchitis, but without obstruction. Only a minority belonged to most severe GOLD stages. The mean levels of AAT varied as a function of the presence or absence of airflow obstruction in intermediate AATD subjects, but not in PI*MM. Individuals enrolled in AATD detection programmes represent an interesting cohort both for public health and research purposes.

Non classical HLA genes and non-HLA genes in a population of infants at familial risk of atopy.

AIM: We investigated on parental history and IgE serum level in 2588 consecutive newborns to individuate babies "at risk" of atopy at birth and we analysed the polymorphisms of class III region to evaluate the association with immunogenetic markers of HLA: C4A, C4B, LTA, RAGE and TNFA genes; we performed TNF and IgE receptor (FCERB1) physiologically related gene polymorphisms. RESULT: 791 babies/2588 (30.6%) were considered "at risk" for atopy and followed-up: 400 had familial history of atopy (at least one parent or sibling), 256 had IgE >0.35 kUA/l at birth and during the follow-up and 135 were positive for both conditions. The allele C4B2 was significantly more frequent in the sample of babies at risk (22.1% vs 10%, p< 0.001). Furthermore, the mean value of IgE at birth in babies carrying the allele C4B2 was 2.26 KUA/l versus 0.74 KUA/l in those not carrying this allele (p=0.01). No significant association emerged for RAGE at the centromeric end of class III region and for LTA, TNFA at the telomeric one. TNFRI, TNFRII and FCERB1 gene polymorphisms also seemed not implicated. CONCLUSION: Our study confirms that HLA class III region seems involved in familial predisposition to atopy, and C4B gene probably acts as a marker of a more restricted subregion.

[Radiotherapy plus a combination of cisplatin and 5-fluorouracil for locally advanced head and neck neoplasms. Study of feasibility and preliminary results]. / Radioterapia più cisplatino e 5-fluorouracile concomitante nei tumori della testa e del collo localmente avanzati. Studio di fattibilità e risultati preliminari.

In March 1989 we started a feasibility study of combined radio-chemotherapy in patients with locally-advanced head and neck cancer. The first phase of treatment consisted of conventional radiotherapy (2 Gy/day, 5 days/week for a total dose of 70 Gy to primary tumor and +/- 50 Gy to nodes) and cisplatinum (20 mg/m2, i.v., for 4 days) +5FU (200 mg/m2, i.v., for 4 days) every 4th week, during radiant sessions. The second phase of treatment was started about one month after the end of simultaneous chemotherapy and radiotherapy: patients in complete remission received 1 more cycle of chemotherapy, as consolidation, while patients in partial remission received two more cycles of chemotherapy. Non-responding patients received no more chemotherapy. During the second phase the days of cisplatinum and 5FU were 5. Up to April 1990, 17 patients have been included in the study. They were stage III (64%) and IV (36%). The mean administered dose of radiotherapy was 66 Gy (range: 60-70 Gy) to primary tumor and 60 Gy (range: 40-70 Gy) to nodes. The total number of chemotherapy cycles administered during radiant sessions was 37, the mean number of cycles was 2 (range: 1-3), with 100% dose percentage. The interval between cycles was 3 weeks in 84% of patients. The relationship between number of cycles administered and planned cycle was 37/39 (feasibility: 95%). Acceptability was 100% (no patient refused the treatment). Feasibility of the second phase was 77% and acceptability 90% (1 patient refused the treatment). Toxicity was moderate during the first and the second phases. After the first phase 14/15 evaluable patients (92%) had major response (complete remission: 46%). After the second phase 10/10 evaluable patients had a complete remission. In conclusion, this combined treatment is very easy to administer, and very well accepted. Moreover, it yields a high number of objective responses.

Isolated testicular relapse in a boy with acute lymphoblastic leukemia following allogeneic bone marrow transplantation.

About 5-10% of boys with acute lymphoblastic leukemia (ALL) present with isolated testicular relapse. Very frequently these relapses occur during treatment or in the following six months, and in these cases the prognosis is very severe. The patients are usually treated with radiotherapy and chemotherapy or bone marrow transplantation (BMT). Testicular relapses after BMT are relatively rare. We report the case of a child with ALL who presented testicular relapse during therapy and was treated with local radiotherapy (2000 cGy), chemotherapy and allogeneic matched BMT. The preparative regimen consisted of Cyclophosphamide (60 mg/kg/day x 2 days) and total body irradiation (200 cGy x 2/day x 3 days). Engraftment was documented at day + 14. The patient presented again with testicular relapse at day + 146, and was therefore treated with orchiectomy, local radiotherapy and systemic chemotherapy. A marrow relapse followed, however, at day + 284 and the patient died of progressive disease.

[Concomitant therapy with cisplatin and radiotherapy in locally advanced tumors of the cervico-facial area]. / Terapia concomitante con cisplatino e radioterapia nei tumori del distretto cervico-facciale localmente avanzati.

Nineteen patients with locally advanced head and neck cancer were treated from November 1983 to January 1986 with standard loco-regional Radiotherapy: 2 Gy for 5 days/week up to a total dose of 70 Gy and simultaneous Cisplatinum 20 mg/m2 weekly. All patients achieved a response: 10 (52%) obtained a complete remission (CR) and 9 (48%) a partial remission (PR). Four of 9 patients in PR after chemoradiotherapy were disease-free after radical resection of the residual masses, while another patient was completely cured after second-line chemotherapy. The overall CR was then 79% (15/19). The results were analyzed according to the nodal status and showed that: 92% (11/12) of patients with initial nodal involvement (N1-2) achieved a CR and 75% of them were disease-free after a median follow-up of 23+ months, while only 57% (4/7) of patients with advanced nodal involvement (N3) obtained a CR (p greater than 0.05; NS) and 28% (2/7) of them were alive without evidence of disease (p less than 0.05) after 4+ and 30+ months. Toxicity was moderate: nausea and vomiting (grade 2-3) occurred in about 50% of patients, mucosal toxicity (grade 1-2) in 58%. Myelosuppression was negligible. No patient developed renal failure. Weekly cisplatinum administration during radiotherapy deserves further study especially in the management of patients with advanced primary tumor and minimal lymph node involvement.