In Vitro Effects of Retinoids on the Proliferation and Differentiation Features of Epstein-Barr Virus-Immortalized B Lymphocytes

Retinoids have been shown to be effective in the chemoprevention and treatment of certain human malignancies. In this review, we will summarize our recent results concerning the effects of retinoids on the proliferation and differentiation of Epstein-Barr virus (EBV)-immortalized lymphoblastoid B-cell lines (LCLs), an in vitro model of EBV-related lymphoproliferative disorders arising in immunosuppressed hosts. Retinoids proved to be powerful inhibitors of the proliferation of EBV-infected LCLs in vitro, with 13-cis-retinoic acid (RA), all-trans-RA, and 9-cis-RA being the most effective compounds. Of note, retinoid-induced growth arrest in vitro appears irreversible at drug concentrations (10-^-6 mol/L) which may be reached in man after oral systemic therapy. The antiproliferative activity exerted by retinoids on LCLs is a generalized phenomenon usually associated with a progressive accumulation in G₀/G₁ phases of treated cells. The strong upregulation of p27^Kipl invariably observed in cells exposed to retinoids may contribute to the decreased number of cycling cells, probably by inhibiting the transition from the G₁ to S phase. Moreover, we obtained evidence indicating that the antiproliferative effects of retinoids are not dependent on the induction of terminal differentiation of EBV-immortalized B lymphocytes. In fact, the modifications induced by retinoids relative to LCL morphology, phenotype (downregulation of CD19, HLA-DR, and s-Ig, and upregulation of CD38 and c-Ig), and IgM production were highly variable among the lines tested and often only slightly relevant. Finally, the antiproliferative activity exerted by retinoids on LCLs is not mediated by a direct modulation of viral latent antigens, since EBNA-2 and LMP-1 downregulation was a late event detected only in some cell lines. These results indicate that retinoids may be useful in the medical treatment of EBV-related lymphoproliferative disorders of immunosuppressed patients, particularly in the earlier phases of these diseases.     

Suppression of maintenance of alcohol-drinking behavior by the concurrent availability of saccharin in Sardinian alcohol-preferring (sP) rats.

In the current study, we investigated the effect of the concurrent presentation of saccharin on the maintenance of alcohol-drinking behavior in selectively bred Sardinian alcohol-preferring (sP) rats. Rats were initially given access to alcohol [10% (volume/volume) in water] and water under the home cage, two-bottle, free-choice regimen, with unlimited access for 24 h/day for eight consecutive weeks. Next, a third bottle, containing saccharin [0%, 0.01%, 0.1%, 1%, or 3% (weight/volume) in water], was concomitantly offered for an additional 10 consecutive days. Intake of saccharin solution resulted as an inverted-U function of saccharin concentration, with the 0.1% saccharin solution being the highest accepted. Alcohol intake was a U function of saccharin concentration, being reduced by 65%-95% in the group of rats exposed to the 0.1% saccharin solution. These results indicate that (1) the concurrent presentation of highly palatable solutions of saccharin markedly reduced alcohol intake in alcohol-experienced sP rats and (2) the reducing effect of saccharin solutions on the alcohol intake in sP rats was positively related to their degree of acceptability. We hypothesized that saccharin solutions may have functioned as a reinforcer, partially substituting for alcohol reinforcement and rendering alcohol drinking less urgent.     

Comparing 3DCRT and inversely optimized IMRT planning for head and neck cancer: equivalence between step-and-shoot and sliding window techniques.

BACKGROUND AND PURPOSE: To investigate the feasibility and the advantages of using Intensity-Modulated Radiotherapy (IMRT) for the treatment of head-and-neck cancer. Comparing different methods to deliver IMRT in this clinical setting. MATERIALS AND METHODS: Seven patients (four radical; three post-operative), treated on a 6MV Varian Linac (equipped with an 80 leaves MLC) in accordance with a routine 3DCRT plan, were replanned. Original treatment plans were computed to irradiate a primary Planning Target Volume (PTV1, 54 Gy) and then to perform a boost on a PTV2 (radical: 70.2 Gy; post-operative: 64.8 Gy). IMRT dose plans were inversely-optimized using appropriate constraints with the Helios tool on a Varian Eclipse system. Once the optimal fluences were calculated, different modalities to deliver IMRT were considered: Sliding Window (SW) and Step and Shoot (SS) techniques using a different number of intensity levels to approximate the optimal fluences (e.g. 5, 10 and 20). Mean dose, maximum dose and a number of dose-volume parameters regarding CTV1, CTV2, PTV1, PTV2, OARs (spinal and planning spinal cord, parotids, optical structures, brain and temporal mandibular joint) were considered to compare the five modalities (3DCRT, SW, SS5, SS10, SS20); the Conformity Index (CI), the Irradiated Volume (IV) and the Treated Volume (TV) were also considered in the comparison. RESULTS: A more uniform coverage of the PTV in the IMRT dose plans with respect to the 3DCRT plan was found (for PTV2: V90% = 94.3 for 3DCRT, 97.6 for SS5, 98 for SS10 and 98.1 for SW; V107% = 20.7 for 3DCRT, 5.9 for SS5, 2 for SS10 and 1.3 for SW). Concerning OARs, they all present a significant reduction of mean and/or maximum dose and dose-volume patterns assessed from DVHs: in particular the mean dose of parotids decrease on average of about 13.5Gy passing from 3DCRT to IMRT with an average reduction of NTCP ranging from about 20% to more than 40% for radically treated patients, depending on the chosen end-point. IV and TV are also slightly smaller with IMRT. The results obtained with SS techniques employing 10 or more intensity levels are comparable with those obtained with SW; no differences between SS10 and SW may be appreciated when considering the DVHs of PTV, CTV and OARs. On the other hand, in some cases SS5 may be slightly sub-effective with respect to SS10-SW when considering PTV coverage and Dmax of the spinal cord. CONCLUSIONS: With the Varian planning and delivery system, Step-and-shoot approximations of inversely optimised fluences in head-neck IMRT compare well with SW delivery, even with only five intensity levels. With a number of intensity level of 10 or more, no differences can be appreciated in PTV coverage/OAR sparing with respect to SW.     

Traditional vs wireless intragastric pH monitoring: are the two techniques comparable?

Background Few data are available comparing intragastric pH measured with the traditional catheter‐based and the more recent wireless system (Bravo), and also comparing intraesophageal and intragastric pH during reflux events. Aims of our study were to elucidate these points. Methods Eleven subjects with functional dyspepsia underwent placement of a Bravo capsule 9 cm below the squamo‐columnar junction (SCJ) and of a dual‐electrode catheter, so that the distal electrode was located 9 cm below and the proximal one 6 cm above the SCJ. Key Results The wireless system showed lower intragastric pH than the traditional catheter in the postprandial period (median 2.2 wireless vs 2.7 catheter, P < 0.05) but not in the whole 24 h. Moreover, during the 24 h, minimum intraesophageal pH during reflux events was lower than the simultaneous pH in the gastric body recorded using the catheter (2.2 vs 2.4, P < 0.01) and in the postprandial period lower than the one recorded using both techniques (2.3 vs 2.8 wireless and 3.2 catheter, P < 0.001). Conclusions & Inferences (i) after meals, in the 1st 2 h postprandial pH in the gastric body is significantly lower when measured with the wireless capsule than with the traditional catheter, presumably because of less buffering by food in proximity of the mucosa, (ii) during reflux events intraesophageal pH is lower than pH in the gastric body, in accordance with the notion of greater intragastric acidity in the subcardial region.     

Esophagogastric cancer after bariatric surgery: systematic review of the literature

BackgroundBecause the number of patients with a previous bariatric procedure continues to rise, it is advisable for bariatric surgeons to know how to manage the rare event of the development of an esophagogastric cancer. The aim of the study was to perform a systematic review of all reported cases of esophagogastric cancers after bariatric surgery.MethodsSystematic review of English and French written literature in MEDLINE and EMBASE database.ResultsGlobally, 28 articles describing 33 patients were retrieved. Neoplasms were diagnosed at a mean of 8.5 years after bariatric surgery (range 2 months–29 years). There were 11 esophageal and 22 gastric cancers; although adenocarcinoma represented most cases (90.6%), a tubulovillous adenoma with high-grade atypia, an intramural gastrointestinal stromal tumor, and a diffuse large B-cell lymphoma of the gastric fundus were also reported. Node involvement was reported in 14 cases, and distal metastases in 5. The most frequently reported symptoms were dysphagia and food intolerance, vomiting, epigastric pain, and weight loss. Surgery was performed in 28 patients, although 4 underwent only chemotherapy and/or radiotherapy and 1 received palliative care. Reported mortality rate was 48.1%.ConclusionsTo date, it is not possible to quantify the incidence of esophagogastric cancer after bariatric surgery because of the paucity of reported data. Nevertheless, because the main concern is the delay in diagnosis, it is of critical importance to carefully evaluate any new or modified upper digestive tract symptom occurring during bariatric surgery follow-up.     

An unusual case of postaxial polydactyly of the feet

Polydactyly is a fairly common congenital anomaly characterized by additional fingers and/or toes, generally divided into three groups: medial ray (preaxial) and central and lateral ray (postaxial). We present a case of postaxial (fibular) polydactyly of the feet, assaying its clinical and radiological features and the method of surgical correction. Clinical outcomes after initial surgery were excellent in both feet. This surgical case shows that a careful individual preoperative planning is necessary to achieve good functional and cosmetic outcome. Level of Evidence: Level V, therapeutic study.