Hypofractionation vs. conventional radiotherapy fractionation in the conservative treatment of T1 glottic cancer: a prospective cohort study

Definitive radiotherapy is an effective single-modality in T1 glottic cancer. Hypofractionated schemes could offer excellent results in a shorter treatment period. We aimed to evaluate the clinical outcomes and toxicity comparing conventional vs. hypofractionated radiotherapy treatment in T1N0M0-glottic cancer. Between Jan-1st, 2005 and August-1st, 2017, in a prospective cohort study, with 10-year follow-up, 138 patients were treated with conventional schedule 2 Gy/day, total dose 70 Gy/7 weeks (N = 71) or hypofractionated schedule 2, 2–2, 25 Gy/day, total dose 63, 8–63 Gy/5, 5 weeks (N = 67). Endpoints were clinical-response rate, local relapse-free survival (LRFS), laryngectomy-free survival (LFS), toxicity rates, relapse-free survival (RFS), metastasis-free survival (MFS), second tumour-free survival (2TFS), and overall survival (OS). All patients showed a complete clinical response. No differences were found for LRFS (p = 0.869), LFS (p = 0.975), RFS (p = 0.767), MFS (p = 0.601), 2TFS (p = 0.293), or OS (p = 0.685). Acute toxicity for skin and mucosae was similar (p = 0.550 and p = 0.698). Acute laryngeal toxicity was higher in the hypofractionation group (p = 0.004), due to an increase in slight moderate grade. No differences in late laryngeal edema were found (p = 0.989). Radiotherapy offers high rate survival, local control, and larynx preservation after 5–10-year follow-up. A hypofractionation could be preferable, since it offers the same results as conventional with fewer treatment sessions.     

Multi-day radon signals with a radioactive decay limb -- occurrence and geophysical significance.

Multi-day signals, generally with duration of 2-10 days, are a prominent temporal variation type of radon (Rn) in geogas in the unsaturated zone. Rare multi-day Rn signals have been found which are characterized by: (a) a declining limb lasting up to 10 days which conforms to the radioactive decay of Rn, (b) recurs at the same location and (c) is recorded in diverse situations-volcanic and seismogenic. It suggested that a Rn blob is injected at a lower level on a steady upward flow of geogas whereby the rise and final fall of the signal are attributed to the edges of the blob while the central Rn-decay segment records the passing of the decaying blob itself. Rn-decay signals are a small subset of multi-day Rn signals which are considered as highly irregular and unusable for the understanding of geophysical processes. In difference, it is concluded that multi-day Rn signals are probably proxies of subtle geodynamic processes at upper crustal levels and are therefore significant for studying such processes.     

The effects of grass pollen allergoid immunotherapy on clinical and immunological parameters in children with allergic rhinitis

Allergoid immunotherapy is a new form of allergen immunotherapy allowing safe administration of high allergen doses. There is limited information on the effects of allergoid immunotherapy in children with allergic rhinitis. To investigate the immunological and clinical effects of allergoid immunotherapy in children with allergic rhinitis due to grass pollen allergy. Children with allergic rhinitis were assigned to allergoid immunotherapy (n = 27) or control (n = 26, no immunotherapy) groups. Children in the immunotherapy group received seven injections of grass pollen allergoid immunotherapy before grass pollen season and continued to receive maintenance immunotherapy for 27 months. All patients were offered a pharmacotherapy regimen to be used on demand during the pollen seasons. Clinical and laboratory parameters were compared between the immunotherapy and control groups. The rhinoconjunctivitis symptom-medication score and asthma symptom score were lower in the immunotherapy group after 1 yr of maintenance immunotherapy (p < 0.01 for both). Skin test reactivity and nasal reactivity as determined by nasal provocation testing for grass pollen were significantly decreased after 1 yr of immunotherapy (p < 0.001 for both). The seasonal increase in bronchial reactivity and nasal lavage eosinophil cationic protein levels were prevented after the first year of immunotherapy (p < 0.05 for both). The seasonal increase in immunoglobulin (Ig)E decreased (p < 0.05) and grass-specific IgG, IgG(1) and IgG(4) increased significantly already at the end of the seven-injection build-up therapy (p < 0.001, for all). Interleukin (IL)-4 levels in the culture supernatants showed a steady decline from baseline at first and second year of immunotherapy (p < 0.001) but remained unchanged in the control group. Allergoid immunotherapy is an effective method in the treatment of grass pollen-induced allergic rhinitis in children and prevents the seasonal increase in bronchial hyper-reactivity. Changes in specific IgE and IgG levels and decreased IL-4 production in peripheral blood mononuclear cell culture supernatants may account for the observed clinical effects.     

The role of stem cells in suppurative environments

Purpose:  To evaluate all consecutive patients treated with infliximab for hidradenitis suppurativa (HS).
Patients and methods:  Within 1 year, all consecutive patients seen in our department for HS (1) resistant to usual medical therapies (2) which could not be easily cured by surgery (3) not treated with new medication within 2 months before inclusion were treated intravenously with infliximab (5 mg/kg) without corticosteroids premedication. Four infusions were planned (week 0, week 2, week 6 and week 10) before the interruption of therapy and follow-up. Clinical activity of HS and quality of life of the patients were assessed immediately before the first, the third and the fourth infusions of infliximab.
Results:  Seven patients were included. Five completed the four infusions. Two patients received only three infusions because of severe side effects. The Sartorius score moderately improved with infliximab (mean score at week 0: 94 ± 39, at week 6: 71 ± 38 and at week 10: 83 ± 48). At week 6, patients judged the efficacy of therapy as marked ( n  = 1), moderate ( n  = 4) or null ( n  = 2). At week 10, five patients were evaluated and judged this efficacy as marked ( n  = 2), moderate ( n  = 2) or null ( n  = 1). The mean Skindex-29 score varied from 22 ± 11 (E: 25 ± 9, S: 13 ± 5, F: 28 ± 12) at week 0 to 18 ± 10 (E: 22 ± 8, S: 12 ± 8, F: 22 ± 12) at week 10.
Conclusion:  The efficacy of infliximab in severe HS is partial. More experience is needed before finding a place for infliximab in the therapeutic armamentarium for HS.     

The diagnostic utility of immunohistochemistry and electron microscopy in distinguishing between peritoneal mesotheliomas and serous carcinomas: a comparative study.

The histologic distinction between peritoneal epithelioid mesotheliomas and serous carcinomas diffusely involving the peritoneum may be difficult, but it can be facilitated by the use of immunohistochemistry and electron microscopy. D2-40 and podoplanin are two recently recognized lymphatic endothelial markers that can be expressed in normal mesothelial cells and mesotheliomas. The purpose of this study is to compare the value of these new mesothelial markers with those that are commonly used for discriminating between mesotheliomas and serous carcinomas, and also to determine the current role of electron microscopy in distinguishing between these malignancies. A total of 40 peritoneal epithelioid mesotheliomas and 45 serous carcinomas of the ovary (15 primary, 30 metastatic to the peritoneum) were investigated for the expression of the following markers: D2-40, podoplanin, calretinin, keratin 5/6, thrombomodulin, MOC-31, Ber-EP4, B72.3 (TAG-72), BG-8 (Lewis(Y)), CA19-9, and leu-M1 (CD15). All 40 (100%) of the mesotheliomas reacted for calretinin, 93% for D2-40, 93% for podoplanin, 93% for keratin 5/6, 73% for thrombomodulin, 13% for Ber-EP4, 5% for MOC-31, 3% for BG-8, and none for B72.3, CA19-9, or leu-M1. All 45 (100%) serous carcinomas were positive for Ber-EP4, 98% for MOC-31, 73% for B72.3, 73% for BG-8, 67% for CA19-9, 58% for leu-M1, 31% for keratin 5/6, 31% for calretinin, 13% for D2-40, 13% for podoplanin, and 4% for thrombomodulin. After analyzing the results, it is concluded that Ber-EP4 and MOC-31 are the best negative mesothelioma markers for differentiating between epithelioid mesotheliomas and serous carcinomas. The best discriminators among the positive markers for mesotheliomas are D2-40, podoplanin, and calretinin. From a practical point of view, Ber-EP4 and MOC-31, in combination with calretinin, and/or D2-40 or podoplanin allow the differential diagnosis to be established between mesothelioma and serous carcinoma in nearly all instances. As a clear distinction could be made between these two malignancies in all of the cases in which electron microscopy was performed, this technique can be very useful in establishing the correct diagnosis when the immunohistochemical results are equivocal or further support of a diagnosis of either mesothelioma or serous carcinoma is needed.     

Osteogenic alveolar distraction: a review of the literature.

OBJECTIVE: Alveolar distraction is a relatively novel procedure by which alveolar bone and underlying mucosa are regenerated. The low predictability of other vertical or horizontal bone regeneration methods has increased interest in this promising technique. This article was designed to review published clinical and experimental results on alveolar distraction, including basic research in other disciplines (maxillofacial and orthopedic distraction) related to or with influence on alveolar distraction. STUDY DESIGN: A review of the international literature was performed to summarize results of clinical and experimental studies on alveolar distraction and on distraction at other anatomical sites that contribute important findings on tissue biology, molecular mechanisms, and other factors that influence and participate in the alveolar distraction process. RESULTS: Research into alveolar distraction has addressed the latency phase, distraction phase, and consolidation phase, yielding highly variable results. Little experimental research has been carried out on this procedure, and most publications are clinical studies with a short follow-up period. Published studies have reported a high rate of complications, attributable to our current lack of understanding of the process. CONCLUSIONS: Definitive conclusions on alveolar distraction are hampered by the lack of clinical and experimental studies to date. Greater knowledge of the factors that influence the distraction process will lead to a more predictable and efficacious distraction technique and a better distractor design.     

Altered apoptosis in bronchoalveolar lavage lymphocytes after allergen exposure of atopic asthmatic subjects.

The increased number of lymphocytes in airways during an asthmatic response is believed to be the result of increased recruitment of these cells. However, it is possible that a decreased apoptotic rate could also contribute to the increased number. The aim of the present study was to investigate whether allergen airway provocation influences the apoptotic phenotype of lung and peripheral blood lymphocytes (PBL) in subjects with atopic asthma. Bronchoalveolar lavage (BAL) lymphocytes and PBL from 12 asthmatic subjects previously challenged with allergen (n = 7) or saline (n = 5) were exposed to the apoptotic stimulus tributyltin (TBT) in vitro and assayed for apoptosis. Airway allergen provocation resulted in decreased sensitivity of BAL lymphocytes to TBT-induced apoptosis, with 42.2% (range 33.9-62.5%) apoptotic cells before challenge versus 23.5% (range 15.3-42.4%) after challenge, while PBL were unaffected. The increased apoptosis resistance correlated with higher numbers of Bcl-2-expressing lymphocytes. Interestingly, baseline caspase-3-like activity was significantly elevated in viable BAL lymphocytes compared with viable PBL, and was unaltered by allergen exposure. In conclusion, allergen inhalation renders bronchoalveolar lavage lymphocytes more resistant to apoptosis while peripheral blood lymphocytes were not influenced at all, indicating that the apoptotic phenotype of airway lymphocytes may play a role in asthmatic inflammation.