Outcome after supracricoid laryngectomies in the material of ENT Department, Poznan University of Medical Sciences

All patients with T1 and T2 laryngeal cancer should be treated with the intent to preserve the larynx. In T3 glottic low-volume tumors, larynx preservation is an appropriate standard treatment option. Supracricoid partial laryngectomy remains a reasonable alternative to radiotherapy for patients with T2–T3 glottic cancer. Prospective clinical study aims to evaluate the oncological results of supracricoid partial laryngectomy as a treatment for selected glottic and supraglottic carcinoma, and to determine the different prognostic factors that may influence local control and survival. In the period of 2000–2007, 145 patients were treated at the academic tertiary referral medical center: ENT Department, University of Medical Sciences, Poznán, Poland. The ages of the analyzed group of patients ranged from 23 to 79, with mean 56.5 age for men and 25 for women. All of the patients had biopsy proven squamous cell carcinoma. Of the 145 patients 82 had glottic cancer and 63 had supraglottic cancer. The patients were staged according to the 2003 edition of the TNM classification established by the AJCC. The pathological TNM classification was additionally taken into consideration. All patients were treated by means of supracricoid and transglottic partial laryngectomy. The type of supracricoid partial laryngectomy was based on tumor localization and extension. Four patients underwent cricohyoidopexy, 57 cricohyoidoepiglottopexy, 65 reconstruction modo Calearo, and 19 modo Sedlacek-Tucker. We performed 21 unilateral selective neck dissections and none bilateral. A nasogastric feeding tube was inserted in all patients, and removed in patients that regained proper swallowing. As a result, we took into consideration the oncological and functional results. Histopathological examination of the operating specimen revealed the presence of dysplasia or invasive carcinoma at the margins, or a close margin of less than 5 mm from the edge of the resection (16 cases). The metastases were found on the neck in three cases, predominantly in the level II (2 cases) and III (1 case). Metastasis was found in one patient that had undergone CHP, Sedlacek-Tucker, and Calearo, respectively. Five patients received postoperative radiotherapy. The decision to use adjuvant radiotherapy was based on the presence of invasive carcinoma at the resection margin and on the presence of multiple positive neck nodes or extracapsular spread of the disease. The Kaplan–Meier estimated 3- and 5-year overall survival rates in the group of 122 because 23 patients did not report for medical check-ups

CYFRA 21-1 level predicts survival in non-small-cell lung cancer patients receiving gefitinib as third-line therapy

Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKI) as gefitinib emerged as an accepted treatment in second- or third-line setting in NSCLC. However, clinical surrogate markers of EGFR-TKI activity in NSCLC patients remain to be identified and we studied the prognostic value of CYFRA 21-1 in this setting. Serum samples from 53 patients with NSCLC receiving gefitinib after failure of at least a platinum-containing regimen were prospectively collected from January 2002 to December 2003. Multivariate analysis demonstrated an independent negative impact on survival for a level of CYFRA 21-1 higher than 3.5 ng ml−1 (HR=2.45, 95% CI 1.13–5.29; P=0.02). In conclusion, CYFRA 21-1 is a tool available to predict the survival of NSCLC patients receiving gefitinib as third-line therapy in an independent manner. In case of a CYFRA 21-1 level higher than 3.5 ng ml−1, treatment with gefitinib needs further evaluation giving its relative poor effect on survival

An investigation of intensity-modulated radiation therapy versus conventional two-dimensional and 3D-conformal radiation therapy for early stage larynx cancer

<p>Abstract</p> <p>Introduction</p> <p>Intensity modulated radiation therapy (IMRT) has been incorporated at several institutions for early stage laryngeal cancer (T1/T2N0M0), but its utility is controversial.</p> <p>Methods</p> <p>In three representative patients, multiple plans were generated: 1) Conventional 2D planning, with the posterior border placed at either the anterior aspect ("tight" plan) or the mid-vertebral body ("loose" plan), 2) 3D planning, utilizing both 1.0 and 0.5 cm margins for the planning target volume (PTV), and 3) IMRT planning, utilizing the same margins as the 3D plans. A dosimetric comparison was performed for the target volume, spinal cord, arytenoids, and carotid arteries. The prescription dose was 6300 cGy (225 cGy fractions), and the 3D and IMRT plans were normalized to this dose.</p> <p>Results</p> <p>For PTV margins of 1.0 cm and 0.5 cm, the D95 of the 2D tight/loose plans were 3781/5437 cGy and 5372/5869 cGy, respectively (IMRT/3D plans both 6300 cGy). With a PTV margin of 1.0 cm, the mean carotid artery dose was 2483/5671/5777/4049 cGy in the 2D tight, 2D loose, 3D, and IMRT plans, respectively. When the PTV was reduced to 0.5 cm, the the mean carotid artery dose was 2483/5671/6466/2577 cGy to the above four plans, respectively. The arytenoid doses were similar between the four plans, and spinal cord doses were well below tolerance.</p> <p>Conclusions</p> <p>IMRT provides a more ideal dose distribution compared to 2D treatment and 3D planning in regards to mean carotid dose. We therefore recommend IMRT in select cases when the treating physician is confident with the GTV.</p

Rapid Environmental Change over the Past Decade Revealed by Isotopic Analysis of the California Mussel in the Northeast Pacific

The anthropogenic input of fossil fuel carbon into the atmosphere results in increased carbon dioxide (CO2) into the oceans, a process that lowers seawater pH, decreases alkalinity and can inhibit the production of shell material. Corrosive water has recently been documented in the northeast Pacific, along with a rapid decline in seawater pH over the past decade. A lack of instrumentation prior to the 1990s means that we have no indication whether these carbon cycle changes have precedence or are a response to recent anthropogenic CO2 inputs. We analyzed stable carbon and oxygen isotopes (δ13C, δ18O) of decade-old California mussel shells (Mytilus californianus) in the context of an instrumental seawater record of the same length. We further compared modern shells to shells from 1000 to 1340 years BP and from the 1960s to the present and show declines in the δ13C of modern shells that have no historical precedent. Our finding of decline in another shelled mollusk (limpet) and our extensive environmental data show that these δ13C declines are unexplained by changes to the coastal food web, upwelling regime, or local circulation. Our observed decline in shell δ13C parallels other signs of rapid changes to the nearshore carbon cycle in the Pacific, including a decline in pH that is an order of magnitude greater than predicted by an equilibrium response to rising atmospheric CO2, the presence of low pH water throughout the region, and a record of a similarly steep decline in δ13C in algae in the Gulf of Alaska. These unprecedented changes and the lack of a clear causal variable underscores the need for better quantifying carbon dynamics in nearshore environments

Definitive and adjuvant radiotherapy for sinonasal squamous cell carcinomas: a single institutional experience

Background: The aim of this study was to evaluate the disease outcomes of patients treated with definitive and adjuvant radiotherapy for squamous cell carcinomas of the nasal cavity and paranasal sinuses in a single institution. Methods: Between 2007–2012 patients were retrospectively identified from electronic databases who had undergone surgery and adjuvant radiotherapy or definitive radiotherapy for sinonasal squamous cell carcinomas with curative intent. Results: Fourty three patients with sinonasal squamous cell carcinoma were identified (22 nasal cavity, 21 paranasal sinuses). 31/43 (72 %) had T3 or T4 disease; nodal stage was N0 in 38, N1 in 4, Na/b in 0 and N2c in 1 patient. Median age was 67 years (range 41–86). 18 (42 %) received definitive and 25 (58 %) adjuvant radiotherapy. Radiotherapy was delivered using either conventional radiotherapy (n = 39) or intensity modulated radiotherapy (n = 4). Elective neck radiotherapy was delivered to two patients. Chemotherapy was delivered to 6/43 (14 %) of patients. Two-year local control, regional control, distant metastases free survival, progression free survival, cause specific survival and overall survival were 81 %, 90 %, 95 %, 71 %, 84 % and 80 % respectively. There was no significant difference in outcome comparing patients who underwent surgery and adjuvant radiotherapy with patients receiving definitive radiotherapy (2 year locoregional disease free survival 75 % and 70 % respectively, p = 0.98). Pooly differentiated tumours were significantly associated with inferior disease outcomes. Local, regional, combined local and regional, and distant failure occurred in 7 (16 %), 3 (7 %), 1 (2 %) and 2 (5 %) of patients; all 3 regional recurrences were in patients with nasal cavity squamous cell carcinomas who had not undergone elective neck treatment. Conclusions: Definitive or adjuvant radiotherapy provides an effective treatment for sinonasal malignancies. The main pattern of failure remains local, suggesting the need for investigation of intensified local therapy. Whilst remaining uncommon, the cases of regional failure mean that the merits of elective lymph node treatment should be considered on an individual basis

General practice vs surgical-based follow-up for patients with colon cancer: randomised controlled trial

This trial examined the optimal setting for follow-up of patients after treatment for colon cancer by either general practitioners or surgeons. In all, 203 consenting patients who had undergone potentially curative treatment for colon cancer were randomised to follow-up by general practitioners or surgeons. Follow-up guidance recommended three monthly clinical review and annual faecal occult blood tests (FOBT) and were identical in both study arms. Primary outcome measures (measured at baseline, 12 and 24 months were (1) quality of life, SF-12; physical and mental component scores, (2) anxiety and depression: Hospital Anxiety and Depression Scale and (3) patient satisfaction: Patient Visit-Specific Questionnaire. Secondary outcomes (at 24 months) were: investigations, number and timing of recurrences and deaths. In all, 170 patients were available for follow-up at 12 months and 157 at 24 months. At 12 and 24 months there were no differences in scores for quality of life (physical component score, P=0.88 at 12 months; P=0.28 at 24 months: mental component score, P=0.51, P=0.47; adjusted), anxiety (P=0.72; P=0.11) depression (P=0.28; P=0.80) or patient satisfaction (P=0.06, 24 months). General practitioners ordered more FOBTs than surgeons (rate ratio 2.4, 95% CI 1.4–4.4), whereas more colonoscopies (rate ratio 0.7, 95% CI 0.5–1.0), and ultrasounds (rate ratio 0.5, 95% CI 0.3–1.0) were undertaken in the surgeon-led group. Results suggest similar recurrence, time to detection and death rates in each group. Colon cancer patients with follow-up led by surgeons or general practitioners experience similar outcomes, although patterns of investigation vary

The Retrograde IFT Machinery of C. elegans Cilia: Two IFT Dynein Complexes?

We analyzed the relatively poorly understood IFT-dynein (class DYNC2)-driven retrograde IFT pathway in C. elegans cilia, which yielded results that are surprising in the context of current models of IFT. Assays of C. elegans dynein gene expression and intraflagellar transport (IFT) suggest that conventional IFT-dynein contains essential heavy (CHE-3), light-intermediate (XBX-1), plus three light polypeptide chains that participate in IFT, but no “essential” intermediate chain. IFT assays of XBX-1::YFP suggest that IFT-dynein is transported as cargo to the distal tip of the cilium by kinesin-2 motors, but independent of the IFT-particle/BBSome complexes. Finally, we were surprised to find that the subset of cilia present on the OLQ (outer labial quadrant) neurons assemble independently of conventional “CHE-3” IFT-dynein, implying that there is a second IFT-dynein acting in these cilia. We have found a novel gene encoding a dynein heavy chain, DHC-3, and two light chains, in OLQ neurons, which could constitute an IFT-dynein complex in OLQ neuronal cilia. Our results underscore several surprising features of retrograde IFT that require clarification

Nuclear Factor-Kappa B Inhibition Can Enhance Apoptosis of Differentiated Thyroid Cancer Cells Induced by 131I

Objective: To evaluate changes of nuclear factor-kappa B (NF-kB) during radioiodine 131 ( 131 I) therapy and whether NF-kB inhibition could enhance 131 I-induced apoptosis in differentiated thyroid cancer (DTC) cells in a synergistic manner. Methods: Three human DTC cell lines were used. NF-kB inhibition was achieved by using a NF-kB inhibitor (Bay 11-7082) or by p65 siRNA transfection. Methyl-thiazolyl-tetrazolium assay was performed for cell viability assessment. DNA-binding assay, luciferase reporter assay, and Western blot were adopted to determine function and expression changes of NF-kB. Then NF-kB regulated anti-apoptotic factors XIAP, cIAP1, and Bcl-xL were measured. Apoptosis was analyzed by Western blot for caspase 3 and PARP, and by flow cytometry as well. An iodide uptake assay was performed to determine whether NF-kB inhibition could influence radioactive iodide uptake. Results: The methyl-thiazolyl-tetrazolium assay showed significant decrease of viable cells by combination therapy than by mono-therapies. The DNA-binding assay and luciferase reporter assay showed enhanced NF-kB function and reporter gene activities due to 131 I, yet significant suppression was achieved by NF-kB inhibition. Western blot proved 131 I could increase nuclear NF-kB concentration, while NF-kB inhibition reduced NF-kB concentration. Western blot also demonstrated significant up-regulation of XIAP, cIAP1, and Bcl-xL after 131 I therapy. And inhibition of NF-kB could significantly downregulate these factors. Finally, synergism induced by combined therapy was displayed by significant enhancements o