Retraction Notice to: Stem cell and colorectal carcinogenesis.

[This retracts the article on p. 6 in vol. 9, PMID: 27713769.].

Stem cells and colorectal carcinogenesis.

Colorectal cancer represents an important cause of mortality and morbidity. Unfortunately, the physiopathology is still under study. There are theories about carcinogenesis and it is known that not only a single factor is responsible for the development of a tumor, but several conditions. Stem cells are a promising target for the treatment of colorectal cancer, along with the environment that has an important role. It has been postulated that mutations within the adult colonic stem cells may induce neoplastic changes. This theory is based on the observation that within a colon cancer, less than 1% of the neoplastic cells have the ability to regenerate the tumor and therefore they are responsible for recurrence. It is important to know that a new way of treatment needs to be found, since these cells are resistant to chemotherapy and radiotherapy.

Biomarkers in Rheumatoid Arthritis, what is new?

UNLABELLED: Rheumatoid arthritis (RA) is a chronic inflammatory disease with autoimmune pathogenesis. It affects mainly small joints (of the hands and feet) and has many systemic manifestations. Studying biomarkers in rheumatology intensely appeared from the need to understand the mechanisms underlying some rheumatic diseases. Discovering new biomarkers with key roles in various stages of evolution, remains a subject of interest for RA. Currently, according to the EULAR 2010 criteria, the rheumatoid factor (RF) and the anti-cyclic citrullinated peptide (anti-CCP) are used for RA diagnosis. Since 2010, new biomarkers were discovered and proved useful in identifying RA in early stages. For a more rigorous management of these cases, one of the key steps in the evolution of patients with RA is to recognize and distinguish the more aggressive forms of the disease through prognostic biomarkers. "Treat to target" recommends the use of 3 composite scores to monitor the evolution of the disease: disease activity score (DAS 28), simple disease activity index (SDAI) and clinical disease activity index (CDAI), but, a new test was developed which better monitors the disease activity. The introduction of biological therapies has revolutionized the treatment of RA. Despite these advances, 20-40% of the patients are declared nonresponders to at least one of the therapies. The patient exposure to the potential side effects and high costs requires the discovery of a biomarker that could identify those who can benefit from the pretreatment of a certain therapy. ABBREVIATIONS: RA = rheumatoid arthritis, RF = rheumatoid factor, DAS 28 = disease activity score, SDAI = simple disease activity index, CDAI = clinical disease activity index, ACR = American College of Rheumatology, EULAR = European League against Rheumatism, anti-CCP = antibodies against cyclic citrullinated proteins, anti-MCV = mutated citrullinated vimentin antibodies, anti-CarP = antibodies against carbamylated proteins, MBDA = multi biomarker disease activity test, COMP = cartilage oligomeric matrix protein, ADAs = antidrug antibodies, CDA = clinical disease activity index, SDAI = simplified disease activity index, ESR = erythrocyte sedimentation rate, CRP = C reactive protein, SAA = serum amyloid A, VCAM-1 = vascular cell adhesion molecule-1, IL-6 = interleukin-6, TNF-R1 = tumor necrosis factor receptor 1, EGF = epidermal growth factor, VEGF-A = vascular endothelial growth factor A.

Colorectal Chemoprevention.

With over 1 million cases diagnosed worldwide each year - incidence which seems to rise with the progressive westernization of lifestyles in Asian and African populations - colorectal cancer is the third most commonly diagnosed cancer in both men and women. Colorectal neoplasms and/or pre-neoplasms can be prevented by interfering with the various steps of oncogenesis, which begins with uncontrolled epithelial cell replication, continues with the formation of adenomas and eventually evolves into malignancy. The knowledge described herein will help to reduce and prevent this malignancy, which is one of the most frequent neoplasms in some developed countries. Genetics, experimental and epidemiologic studies suggest that colorectal cancer results from complex interactions between inherited susceptibility and environmental factors. Primary prevention involves the identification of genetic, biologic, and environmental factors that are etiologic or pathogenic in the development of cancer, and subsequent complete or significant interference with their effects on carcinogenesis.

The efficiency of biologic therapy in a group of patients with rheumatoid arthritis.

OBJECTIVES: The following study aims to evaluate the monotherapy with biologic agents: Infliximab (IFX), Etanercept (ETA), Adalimumab (ADA) and Rituximab (RTX) in patients diagnosed with rheumatoid arthritis (RA). METHODS: To achieve these objectives, the database of "Dr. I. Cantacuzino" Clinical Hospital, Department of Internal Medicine and Rheumatology, was used. The study was retrospective and descriptive, covering 168 patients with RA, followed for 12 months, from January 2012 to January 2013. Admission criteria for the study were the following: patients diagnosed with RA according to ACR 1987/ EULAR 2010 criteria, disease activity score (DAS 28)> 5.1, positive inflammation tests, presence of RA refractory to classic remitting treatment administered at least 6 months prior to the initiation of biological therapy, on patients treated with RTX. They were considered non-responders after 6 months of treatment with anti tumor necrosis factor alpha (anti-TNF) and decided to switch agents with anti CD-20. RESULTS: Comparing values between any two points in time (baseline - 6 months -12 months) for any type of therapy, there were significant decreases in the values of erythrocyte sedimentation rate (ESR), reactive C protein (CRP) and disease activity score (DAS 28). There were no significant differences between therapies regarding ESR at 6 months (p = 0.070, ANOVA) and 12 months (p = 0.375, Kruskal-Wallis), significant differences were regarding CRP at 6 and 12 months (p = 0.000, Kruskal-Wallis) and DAS 28 at 6 months (p = 0.000, Kruskal- Wallis) and 12 months (p = 0.018, Kruskal-Wallis). CONCLUSION: All 4 therapies have proven efficient, prognostic markers decreasing gradually at 6 and 12 months.

Apoptosis in colorectal cancer.

Apoptosis is an inborn process that has been preserved during evolution; it allows the cells to systematically inactivate, destroy and dispose of their own components thus leading to their death. This programme can be activated by both intra and extracellular mechanisms. The intracellular components involve a genetically defined development programme while the extracellular aspects regard endogenous proteins, cytokines and hormones as well as xenobiotics, radiations, oxidative stress and hypoxia. The ability of a cell to enter apoptosis as a response to a "death" signal depends on its proliferative status, the position in the cell cycle and also on the controlled expression of those genes that have the capacity of promoting and inhibiting cell death. The fine regulation of these parameters needs to be maintained in order to ensure the physiological environment required for the induction of apoptosis. Any malfunction in any of the steps of controlled cellular death can lead to dysfunctions and, as a consequence, to different pathological conditions. The importance of apoptosis lies in its active nature and in the potential of controlling biological systems.

Malignancy and mortality of colorectal polyps.

OBJECTIVES: To evaluate the rate of morbidity and mortality associated with colorectal polyps after the next 8-years period of endoscopic polypectomy, in a high risk managed care population. MATERIAL AND METHOD: Cohorts of 77 subjects with benign neoplasms were identified with a colonoscopy in 1999. Three groups of subjects: benign neoplasms with polypectomy, benign neoplasms without polypectomy, and no neoplasms were evaluated. Five years recurrence rates (1999-2004) of benign or new malignant colorectal neoplasms were identified: for the benign determined for the baseline benign neoplasms with polypectomy and no neoplasm groups neoplasm without polypectomy, only rates for malignancy were observed. Malignancy was evaluated with immunohistochemical p53 (tumor protein 53) and PCNA (Proliferating Cell Nuclear Antigen) staining pattern. Over the next 8 years 2004-2012 were evaluated the mortality and the recurrence rate of the benign polyps. RESULTS: 77 subjects were enrolled in our study; 71.4% were diagnosed with benign and 2.5% with malignant neoplasms. The 5-years cumulative incidence rates of malignant colorectal neoplasms in the no neoplasm (n = 20) and benign neoplasm groups (n = 55) were (n = 1) 5% and ( n = 10) 18.1%, respectively (p < 0.005). A lower 5-years malignancy rate was observed in benign neoplasms group with polypectomy (12%) compared to the benign neoplasm group without polypectomy (33.3%) (p < 0.05). The 8-years mortality rate was compared into benign recurrent polyps group and into malign group: the lower 8-years mortality rate was observed into benign polyp no neoplasm group (0%) and into benign recurrent polyps group (40%); the highest rate was observed into neoplasm group (100%). CONCLUSIONS: The high recurrence rate of benign colorectal neoplasms and a higher incidence of colorectal cancer in subjects at high risk-history of benign colorectal neoplasm-highlight a healthcare opportunity for surveillance and/or interventions to reduce the morbidity associated with colorectal neoplasms.

Technical performance of colonoscopy -- multicenter study in university and non-university centers of Romania.

UNLABELLED: The aim of the paper was to evaluate the national availability of colonoscopy and the quality parameters of this procedure in our country. MATERIAL AND METHOD: During a 6 months period (01.07- 31.12.2009), we performed a prospective multicenter study in which 76 centers were invited to respond to a questionnaire regarding colonoscopy, 39 centers agreeing to participate. We assessed: the number of colonoscopies, the number of total colonoscopies and the causes of incomplete colonoscopies. RESULTS: During the study period, 16,083 colonoscopies were performed, 12,294 (76.4%) of them total colonoscopies. In 1,191 cases, stenosis was the cause of incomplete colonoscopy. If we consider this an objective reason for an incomplete colonoscopy, there were 12,294 total colonoscopies (82.4%). Comparing university centers with non-university ones, the proportion of total colonoscopies was 10,400/12,475 (83.4%) vs. 1,894/2,417 (78.4%) (p less then 0.0001). However, comparing the present study with previous ones, performed in 2003 and 2007, the proportion of total colonoscopies increased from 70.5% to 76.9% and 82.4% respectively (2003 vs. 2007 p less then 0.0001; 2007 vs. 2009 p less then 0.0001), while the quality difference between university and non-university hospitals persisted. CONCLUSIONS: the quality of colonoscopy in Romania increased in the last 5 years, while the quality difference between university and non-university hospitals persisted.

Rheumatoid arthritis: travelling biological era a Romanian X-ray population.

BACKGROUND: Rheumatoid arthritis (RA) is associated with loss of overall functionality of the locomotion system and it is connected with substantial economic losses. OBJECTIVE: To describe the clinical characteristics and healthcare resource utilization characteristics and to analyze the correlations in a cross-sectional sample of 206 patients in Romania. METHOD: RA cases have been enrolled from southern and western part of the country, covering a surface of 23 counties. RESULTS: Particularly in the literature data, Romanian RA patients become work disabled at 5.65 +/- 5.99 years old after the diagnosis. At cohort level, retirement in the first year after RA diagnosis is of 22.9%. From those, 13% were treated with biologic DMARDs; those on non-biologic DMARDs were 28.6%. In oral therapy group the most prescribed drug is lefunomide (61.2%). RA has an important impact on pain, function and utility, influenced by social factors. Patients' follow up is often based on hospitalization. CONCLUSION: Currently, when the clinician may choose for one certain therapy or another, the social influence is still overwhelming at all the evaluation levels in RA patients, as well as at economic impact.

Hypertrophic osteoarthropathy secondary to bronchopulmonary cancer (our experience).

During 5 years (1986-1990), 81 of the patients under our care showed bronchopulmonary cancer diagnosed by clinical, x-ray and bronchoscopic examinations. Of these, 69 (85.2) were men and 12 (14.8%) women, with a mean age of 62 years; 72 patients (90%) were moderate or heavy smokers. Four of them (4.9%) presented the classical hypertrophic osteoarthropathy (HOA) described by Bamberger and Pierre Marie, i.e., finger clubbing, ossifying periostitis of the long bones, joint pains and swelling. Other 3 patients showed only finger clubbing, while 7 of 30 cases studied by systematic x-ray examinations of the long bones presented ossifying periostitis (5 cases) or hyperostosis (2 cases). It results that almost one third (31.6%) of the patients with bronchopulmonary cancer had a complete or incomplete Bamberger-Pierre Marie syndrome. It is concluded that HOA identification before the clinical and x-ray manifestations of bronchopulmonary cancer could contribute to an early diagnosis of this malignant disease.

The Bucharest multifactorial prevention trial of coronary heart disease. General methodology and risk factor correction after five year follow-up (1971-1977).

Both the intervention and the control group included each 5000 men aged 40-60 years, randomly selected by their home address in five districts of the city of Bucharest. The intervention group underwent an "at entry" examination for risk factor detection (high serum cholesterol, high blood pressure, overweight, diabetes, minor ECG abnormalities, family history) and subsequently a five-year multifactorial intervention aimed to reduce the risk factors. Both groups were followed up in this lapse of time for major end-points: myocardial infarction, stroke, sudden death. The qualitative analysis of the results used ten evolution indices based on a quantal counting and lead to a classification of risk factors which allowed the setting up of a strategy for their correction. The quantitative analysis showed the following decreases between the first and the last examination in the intervention group: for serum cholesterol greater than or equal to 250 mg/dl -17%; for cigarettes/day greater than or equal to 15-53%; for overweight greater than or equal to 30% - 13.57%; for high blood pressure -8%; for the overall risk computed by multiple regression -33.8%.