scholarly journals Post-traumatic Complications of Severe Luxations and replanted Teeth

2015 ◽  
Vol 16 (1) ◽  
pp. 13-19 ◽  
Author(s):  
Thiago Farias Rocha Lima ◽  
Juliana Yuri Nagata ◽  
Francisco José de Souza-Filho ◽  
Adriana de Jesus Soares

ABSTRACT Aim The aim of this study was to evaluate the main posttraumatic complications of severe luxation and replanted teeth using clinical and radiographic analyses. Materials and methods Eighty-three patients aged between 7 and 55 years old presenting 180 traumatized teeth that suffered extrusive luxation (n = 67), lateral luxation (n = 69), intrusive luxation (n = 10) and tooth avulsion (n = 34) followed by replantation were evaluated. The follow-up period was 24 months. The complications examined were: pulp canal obliteration, pulp necrosis and root resorption (inflammatory and replacement). Furthermore, the relationship between time elapsed before receiving dental attendance and development of inflammatory resorption was observed. Results Pulp necrosis was the main complication, occurring in 147 teeth (82.7%). All of the teeth that suffered intrusive luxation and tooth avulsion were diagnosed with pulp necrosis, with significant difference in comparison with another traumas (p < 0.001/Fisher's exact test). Inflammatory root resorption was observed in 20.5% of the cases and replacement resorption was more related to tooth replantation (94.1%), showing significant prevalence among tooth luxations (p < 0.001/Fisher's exact test). In addition, it was noted that patients who seek treatment 9 weeks after the trauma episode presented 10 times more chance of developing inflammatory resorption when compared with patients who seek treatment soon after dental trauma (Odds ratio test). Conclusion It may be concluded that pulp necrosis was the main post-traumatic complication observed in traumatized teeth and that delay in seeking treatment may damage the prognosis of severe luxation and replanted teeth. Clinical significance Clinical studies describing the main complications that may affect traumatized teeth present great relevance to make the population aware of the importance of seeking immediate treatment and to alert the professional to the need for follow-up. When traumatic injuries are diagnosed and treated early, post-traumatic complications may be controlled, allowing conservation of the tooth in oral cavity. How to cite this article Lima TFR, Nagata JY, de Souza- Filho FJ, de Jesus Soares A. Post-traumatic Complications of Severe Luxations and replanted Teeth. J Contemp Dent Pract 2015;16(1):13-19.

Author(s):  
Suwartono Herdhana ◽  
Andrijono

Objective: To investigate the effectiveness TCA 85% compared to cryotherapy to treat patients with positive IVA result.Method: This is a non-inferiority randomized controlled trial study. Patients with positive VIA result referred to Jatinegara Primary Health Center were included in this study. Eligible samples were then treated with either TCA 85% or cryotherapy. The treatment was determined using a random block sampling method. Samples were then followed up 3 months after treatment in order to determine VIA result conversion.Result: Thirty-six patients were treated with TCA 85% and 36 others were treated with cryotherapy. 35 (97,2%) patients treated with TCA 85% converted to negative VIA, whereas all of the patients that were treated with cryotherapy converted to negative VIA. Bivariate analysis fisher’s exact test was then conducted with a result P-value of 1.00 (p > 0,05).Conclusion: There was no statistically significant difference of result between TCA 85% and cryotherapy for treating patients with positive VIA result.Keywords: cervical cancer, cryotherapy, TCA 85%, VIA test. Abstrak Tujuan: Mengetahui efikasi TCA 85% pada tatalaksana IVA positif dibandingkan dengan krioterapiMetode: Penelitian ini merupakan penelitian randomized control trial menggunakan metode non-inferiority study. Subyek penelitian ini merupakan pasien dengan hasil IVA positif yang dirujuk ke Puskesmas Kecamatan Jatinegara, Jakarta Timur. Tatalaksana yang diberikan ditentukan menggunakan metode random block sampling. Subyek diikuti selama 3 bulan setelah tindakan untuk menentukan hasil konversi pemeriksaan IVA.Hasil: Sbenyak 36 subjek diterapi dengan TCA 85% dan 36 lainnya diterapi dengan krioterapi. Sebanyak 35 (97,2%) pasien yang ditatalaksana dengan TCA 85% mengalami konversi menjadi IVA negatif pada follow-up bulan ke-3, sedangkan seluruh pasien yang ditatalaksana dengan krioterapi menjadi konversi menjadi IVA negatif. Dilakukan analisis bivariat fisher’s exact test dan didapatkan nilai p sebesar 1,00 (p>0,05).Kesimpulan:Tidak ada perbedaan bermakna dari efikasi penggunaan TCA 85 % dibandingkan dengan krioterapi pada terapi IVA positif.Kata kunci: kanker serviks, krioterapi, pemeriksaan IVA, TCA 85%.


BMC Urology ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Hassan Osman Alhassan Elsaid ◽  
Tarteel Gadkareim ◽  
Tagwa Abobakr ◽  
Eiman Mubarak ◽  
Mehad A. Abdelrhem ◽  
...  

Abstract Background Male factor is the major contributor in roughly half of infertility cases. Genetic factors account for 10–15% of male infertility. Microdeletions of azoospermia factors (AZF) on the Yq region are the second most frequent spermatogenesis disorder among infertile men after Klinefelter syndrome. We detected in our previous study a frequency of 37.5% AZF microdeletions which investigated mainly the AZFb and AZFc. We attempted in this study for the first time to evaluate the frequencies of all AZF sub-regions microdeletions and to analyze reproductive hormonal profiles in idiopathic cases of azoospermic and oligozoospermic men from Sudan. Methods A group of 51 medically fit infertile men were subjected to semen analysis. Four couples have participated in this study as a control group. Semen analysis was performed according to WHO criteria by professionals at Elsir Abu-Elhassan Fertility Centre where samples have been collected. We detected 12 STSs markers of Y chromosome AZF microdeletions using a multiplex polymerase chain reaction. Analysis of reproductive hormone levels including Follicle Stimulating, Luteinizing, and Prolactin hormones was performed using ELISA. Comparisons between outcome groups were performed using Student’s t-test Chi-square test or Fisher’s exact test. Results AZF microdeletion was identified in 16 out of 25 Azoospermic and 14 out of 26 of the Oligozoospermic. Microdeletion in the AZFa region was the most frequent among the 30 patients (N = 11) followed by AZFc, AZFd (N = 4 for each) and AZFb (N = 3). Among the Oligozoospermic participants, the most frequent deletions detected were in the AZFa region (N = 10 out of 14) and was significantly associated with Oligozoospermic phenotype, Fisher's Exact Test (2-sided) p = 0.009. Among the Azoospermic patients, the deletion of the AZFc region was the most frequent (N = 9 out of 16) and was significantly associated with Azoospermia phenotype Fisher's Exact Test p = 0.026. There was a significant difference in Y chromosome microdeletion frequency between the two groups. The hormonal analysis showed that the mean levels of PRL, LH, and FSH in Azoospermic patients were slightly higher than those in oligozoospermic. A weak negative correlation between prolactin higher level and Azoospermic patients was detected. (AZFa r = 0.665 and 0.602, p = 0.000 and 0.0004, AZFb r = 0.636 and 0.409, p = 0.000 and 0.025, and AZFd r = 0.398 and 0.442, p = 0.029 and 0.015). The correlation was positive for AZFa and negative for AZFb and AZFd. Conclusions We concluded in this study that the incidences of microdeletions of the Y chromosome confined to AZF a, b, c and d regions is 58.8% in infertile subjects with 31.4% were Azoospermic and 27.5% were Oligozoospermic. This might provide a piece of evidence that these specified regions of the Y chromosome are essential for controlling spermatogenesis. These findings will be useful for genetic counseling within infertility clinics in Sudan and to adopt appropriate methods for assisted reproduction.


2012 ◽  
Author(s):  
Γεώργιος Γαλανόπουλος

Στόχος της παρούσας διδακτορικής διατριβής ήταν η πειραματική μελέτη της επίδρασης της ιλοπρόστης (ανάλογο της προστακυκλίνης) στην επούλωση αναστομώσεων του παχέος εντέρου επίμυων σε συνθήκες αποφρακτικού ειλεού. Για τη μελέτη χρησιμοποιήθηκαν 80 άρρενες επίμυες, οι οποίοι χωρίστηκαν τυχαιοποιημένα σε 4 (1, 2, 3, 4) ομάδες, με 2 (α, β) ισοδύναμες υποομάδες έκαστη. Στην ομάδα 1 (ελέγχου) και 3 (ιλοπρόστη) διενεργήθηκε τμηματική εντερεκτομή και τελικοτελική αναστόμωση. Στην ομάδα 2 (ειλεός) και 4 (ειλεός και ιλοπρόστη) επιτεύχθηκαν αρχικά συνθήκες αποφρακτικού ειλεού και 24 ώρες μετά διενεργήθηκε τμηματική εντερεκτομή και τελικοτελική αναστόμωση. Η ιλοπρόστη χορηγήθηκε στις ομάδες 3 και 4 σε δόση 2μg/kg Β.Σ. σε 3ml διαλύματος NaCl 0,9% ενδοπεριτοναϊκά, διεγχειρητικά και κάθε ημέρα μέχρι τη θυσία, ενώ αντίστοιχα στις ομάδες 1 και 2 στα πειραματόζωα χορηγούνταν 3ml διαλύματος NaCl 0,9%. Σε κάθε ομάδα τα μισά πειραματόζωα (υποομάδα 1α, 2α, 3α, 4α) θυσιάστηκαν την 4η μετεγχειρητική ημέρα και τα υπόλοιπα (υποομάδα 1β, 2β, 3β, 4β) την 8η. Κατά τη νεκροτομή γινόταν μακροσκοπικός έλεγχος για ρήξη της αναστόμωσης, ύπαρξη περιτονίτιδος ή περιαναστομωτικού αποστήματος καθώς και ποσοτική αξιολόγηση των συμφύσεων σύμφωνα με την κλίμακα Van der Hamm. Ακολουθούσε μέτρηση της πίεσης διάσπασης και στη συνέχεια τμήμα της αναστόμωσης αποστέλλονταν για ιστολογική εξέταση κατά την οποία αξιολογούνταν η φλεγμονώδης αντίδραση (διήθηση από ουδετερόφιλα), η νεοαγγειογένεση, ο αριθμός των ινοβλαστών και η εναπόθεση νεοκολλαγόνου. Η ταξινόμηση των μικροσκοπικών ευρημάτων έγινε σύμφωνα με την κλίμακα Ehrlich και Hunt με τις τροποποιήσεις κατά Phillips. Επιπλέον, προσδιορίστηκε βιοχημικά η συγκέντρωση υδροξυπρολίνης και κολλαγενάσης I επί της αναστόμωσης. Για την συνοπτική παρουσίαση των αποτελεσμάτων υπολογίστηκαν απόλυτες και σχετικές συχνότητες (ποσοστά %), δείκτες κεντρικής τάσης (μέσοι όροι, διάμεσες τιμές) και δείκτες διασποράς (ελάχιστες τιμές, μέγιστες τιμές, τυπικές αποκλίσεις). Για τη σύγκριση των μέσων όρων χρησιμοποιήθηκε το κριτήριο της Ελάχιστης Σημαντικής Διαφοράς (Least Significant Difference-LSD), μετά από την εφαρμογή της μεθόδου ANOVA (Analysis of Variance). Για τις συγκρίσεις των ποσοστών, εφαρμόστηκε ο ακριβής έλεγχος του Fisher (Fisher’s Exact Test). Από την ανάλυση των πειραματικών δεδομένων προέκυψε ότι η ενδοπεριτοναϊκή χορήγηση ιλοπρόστης σε συνθήκες αποφρακτικού ειλεού, έχει ως αποτέλεσμα τον περιορισμό της αρνητικής δράσης του ειλεού στην επούλωση των αναστομώσεων του παχέος εντέρου. Συγκεκριμένα, την 4η και 8η μετεγχειρητική ημέρα ελαττώνει σημαντικά την απώλεια σωματικού βάρους. Επίσης, προάγει τη νεοαγγειογένεση, ενώ συγχρόνως αυξάνει τον πολλαπλασιασμό των ινοβλαστών και τη συγκέντρωση υδροξυπρολίνης. Επιπλέον, την 4η μετεγχειρητική ημέρα ελαττώνει τη φλεγμονώδη αντίδραση και μειώνει τη συγκέντρωση κολλαγενάσης Ι. Σταδιακά, την 8η μετεγχειρητική ημέρα αυξάνει τη σύνθεση νεοκολλαγόνου στην περιοχή της αναστόμωσης. Οι παραπάνω δράσεις έχουν ως αποτέλεσμα την αύξηση της μηχανικής ισχύος των αναστομώσεων, κατά την 4η και 8η μετεγχειρητική ημέρα, όπως αυτή προκύπτει από τη μέτρηση των πιέσεων διάσπασης. Συμπερασματικά, η άμεση μετεγχειρητική ενδοπεριτοναϊκή χορήγηση ιλοπρόστης ενισχύει τους μηχανισμούς επούλωσης και αντισταθμίζει την αρνητική δράση του ειλεού στην επούλωση των αναστομώσεων του παχέος εντέρου.


2014 ◽  
Vol 96 (4) ◽  
pp. 289-293 ◽  
Author(s):  
IG Panagiotopoulou ◽  
D Fitzrol ◽  
RA Parker ◽  
J Kuzhively ◽  
N Luscombe ◽  
...  

Introduction We receive fast track referrals on the basis of iron deficiency anaemia (IDA) for patients with normocytic anaemia or for patients with no iron studies. This study examined the yield of colorectal cancer (CRC) among fast track patients to ascertain whether awaiting confirmation of IDA is necessary prior to performing bowel investigations. Methods A review was undertaken of 321 and 930 consecutive fast track referrals from Centre A and Centre B respectively. Contingency tables were analysed using Fisher’s exact test. Logistic regression analyses were performed to investigate significant predictors of CRC. Results Overall, 229 patients were included from Centre A and 689 from Centre B. The odds ratio for microcytic anaemia versus normocytic anaemia in the outcome of CRC was 1.3 (95% confidence interval [CI]: 0.5–3.9) for Centre A and 1.6 (95% CI: 0.8–3.3) for Centre B. In a logistic regression analysis (Centre B only), no significant difference in CRC rates was seen between microcytic and normocytic anaemia (adjusted odds ratio: 1.9, 95% CI: 0.9–3.9). There was no statistically significant difference in the yield of CRC between microcytic and normocytic anaemia (p=0.515, Fisher’s exact test) in patients with anaemia only and no colorectal symptoms. Finally, CRC cases were seen in both microcytic and normocytic groups with or without low ferritin. Conclusions There is no significant difference in the yield of CRC between fast track patients with microcytic and normocytic anaemia. This study provides insufficient evidence to support awaiting confirmation of IDA in fast track patients with normocytic anaemia prior to requesting bowel investigations.


2019 ◽  
Vol 131 (6) ◽  
pp. 1805-1811
Author(s):  
Andrew I. Yang ◽  
Brendan J. McShane ◽  
Frederick L. Hitti ◽  
Sukhmeet K. Sandhu ◽  
H. Isaac Chen ◽  
...  

OBJECTIVEFirst-line treatment for trigeminal neuralgia (TN) is pharmacological management using antiepileptic drugs (AEDs), e.g., carbamazepine (CBZ) and oxcarbazepine (OCBZ). Surgical intervention has been shown to be an effective and durable treatment for TN that is refractory to medical therapy. Despite the lack of evidence for efficacy in patients with TN, the authors hypothesized that patients with neuropathic facial pain are prescribed opioids at high rates, and that neurosurgical intervention may lead to a reduction in opioid use.METHODSThis is a retrospective study of patients with facial pain seen by a single neurosurgeon. All patients completed a survey on pain medications, medical comorbidities, prior interventions for facial pain, and a validated pain outcome tool (the Penn Facial Pain Scale). Patients subsequently undergoing neurosurgical intervention completed a survey at the 1-month follow-up in the office, in addition to telephone interviews using a standardized script between 1 and 6 years after intervention. Univariate and multivariate logistic regression were used to predict opioid use.RESULTSThe study cohort consisted of 309 patients (70% Burchiel type 1 TN [TN1], 18% Burchiel type 2 [TN2], 6% atypical facial pain [AFP], and 6% TN secondary to multiple sclerosis [TN-MS]). At initial presentation, 20% of patients were taking opioids. Of these patients, 55% were receiving concurrent opioid therapy with CBZ/OCBZ, and 84% were receiving concurrent therapy with at least one type of AED. Facial pain diagnosis (for diagnoses other than TN1, odds ratio [OR] 2.5, p = 0.01) and facial pain intensity at its worst (for each unit increase, OR 1.4, p = 0.005) were predictors of opioid use at baseline. Neurosurgical intervention led to a reduction in opioid use to 8% at long-term follow-up (p < 0.01, Fisher’s exact test; n = 154). Diagnosis (for diagnoses other than TN1, OR 4.7, p = 0.002) and postintervention reduction in pain at its worst (for each unit reduction, OR 0.8, p < 10−3) were predictors of opioid use at long-term follow-up. On subgroup analysis, patients with TN1 demonstrated a decrease in opioid use to 5% at long-term follow-up (p < 0.05, Fisher’s exact test), whereas patients with non-TN1 facial pain did not. In the nonsurgical group, there was no statistically significant decrease in opioid use at long-term follow-up (n = 81).CONCLUSIONSIn spite of its high potential for abuse, opioid use, mostly as an adjunct to AEDs, is prevalent in patients with facial pain. Opportunities to curb opioid use in TN1 include earlier neurosurgical intervention.


2001 ◽  
Vol 47 (4) ◽  
pp. 645-653 ◽  
Author(s):  
Anne Mette Høgh ◽  
Thomas Vauvert F Hviid ◽  
Britta Christensen ◽  
Steen Sørensen ◽  
Rasmus D Larsen ◽  
...  

Abstract Background: Information about the appearance of γ-, ε-, and ζ-globin mRNAs in fetal erythroblasts during gestation and about the presence and amounts of these mRNAs in pregnant and nonpregnant women is important from the perspective of using these molecules as a marker of fetal erythroblasts. A specific marker is necessary for isolation and identification of fetal nucleated red blood cells from maternal blood samples for use in antenatal diagnosis of fetal genetic or chromosomal abnormalities. Methods: We used a very sensitive reverse transcription-PCR (RT-PCR) method, coamplification analysis of γ- and ε-globin cDNA, and quantitative analysis of γ-globin mRNA based on competitive RT-PCR to investigate these aspects. Results: All adult whole-blood samples were negative for ε- and ζ-globin mRNA. Analyses of CD71+ cell fractions showed that specimens from 19 of 20 nonpregnant and 10 of 14 pregnant women (at 9–13 weeks of gestation) were positive for γ-globin mRNA (Fisher’s exact test, P = 0.13), and those from 3 of 20 nonpregnant and 5 of 14 pregnant women were positive for ζ-globin mRNA (Fisher’s exact test, P = 0.23). No ε-globin mRNA was detected in CD71+ cell fractions from 1-mL blood samples from adults. CD71+ cell fractions from eight fetal blood samples (at 17–20 weeks of gestation) were positive for all three globin mRNAs. We found no statistically significant difference between the amounts of γ-globin mRNA in pregnant and nonpregnant women. Conclusions: This study indicates that ε-globin mRNA might function as a marker for fetal CD71+ cells early in pregnancy. Although γ-globin mRNA can be detected in CD71+ cell fractions from most adults, these transcripts also may be of use because of a marked difference between adult and fetal values.


Diagnostics ◽  
2020 ◽  
Vol 10 (5) ◽  
pp. 255 ◽  
Author(s):  
Enrica Marchionni ◽  
Maria Grazia Porpora ◽  
Francesca Megiorni ◽  
Ilaria Piacenti ◽  
Agnese Giovannetti ◽  
...  

Background: Endometriosis is a widespread multifactorial disease in which environmental, genetic, and epigenetic factors contribute to the phenotype. Single Nucleotide Polymorphisms (SNPs) in genes implicated in pivotal molecular mechanisms have been investigated as susceptible risk factors in distinct populations. Among these, Toll-like receptor 4 (TLR4) represents a good candidate due to its role in the immune/inflammatory response and endometriosis pathogenesis. Methods: The TRL4 gene T399I SNP (C/T transition, rs4986791) was investigated in 236 Italian endometriosis patients and 150 controls by using the PCR-RFLP method. One-tailed Fisher’s exact test was used to compare differences between categorical variables. T399I genotype distribution was evaluated for Hardy–Weinberg equilibrium in both groups using the Chi-squared test for given probabilities. Results: Fisher’s exact test comparing C and T allele frequencies showed a difference in the frequency of T alleles between patients and controls (OR = 1.96, 95% confidence interval 0.91–4.23; p-value = 0.0552). Genotype frequencies did not show any significant difference between patients and controls. The homozygous TT genotype was observed in 2% of endometriosis women and not in controls. Conclusions: Our results show that the TLR4 rs4986791 T variant may be considered a genetic risk factor for endometriosis in Italian women. More extensive studies in other populations are needed to confirm this result.


2019 ◽  
Vol 57 (03) ◽  
pp. 304-311 ◽  
Author(s):  
Zhongqing Zheng ◽  
Chunshan Zhao ◽  
Shuai Su ◽  
Xiaofei Fan ◽  
Wei Zhao ◽  
...  

Abstract Background and aims On the basis of lesser rates of major adverse events and a short-term efficacy as Heller’s myotomy, there is a growing enthusiasm in favor of peroral endoscopic myotomy (POEM), whereas study comparing POEM and pneumatic dilatation (PD) is quite rare. The aim of this study was to evaluate the efficacy of POEM and PD in Chinese achalasia patients in a retrospectively designed study. Methods Patients with achalasia, who underwent either PD (n = 26) or POEM (n = 40) were retrospectively recruited from September 2010 through March 2016 at a single tertiary center. During the 1-year follow-up, clinical outcome and functional data of lower esophageal sphincter (LES) were recruited. Clinical symptoms were assessed by use of the Eckardt score. The primary outcome was therapeutic success (Eckardt score ≤ 3). Functional data of LES (4-second integrated relaxation pressure [4s-IRP], LES relax rate, and LESP) at baseline and 1 month after treatment were also evaluated. Data was analyzed by SPSS 13.0 version using a significance level of p < 0.05. Results The success rates were 24/26 (92.31 %), 25/26 (96.15 %), and 24/26 (92.31 %), respectively, with POEM, as compared with 35/40 (87.50 %), 29/40 (72.50 %), and 23/40 (57.50 %), respectively, with PD, 1 month, 3 months, and 1 year after treatment. Statistically significant difference was observed between the 2 therapies (at 3 months, Fisher’s exact test, p = 0.01; at 1 year, Fisher’s exact test, p < 0.0001). Compared with PD, the Eckardt score was lower with POEM 1 month, 3 months, and 1 year after treatment. More patients in POEM group reported gastroesophageal reflux symptoms (after 3 months 7/26 (26.92 %) vs. 2/40 (5.00 %), Fisher’s exact test, p = 0.01; after 1 year 6/26 (19.23 %) vs. 1/35 (2.86 %), Fisher’s exact test, p = 0.02). The postoperative 4s-IRP and LESP were both lower with POEM than with PD, respectively. Type I achalasia had a better response with POEM than with PD. Conclusion In this retrospective analysis with 1-year follow-up, POEM presents with a higher success rate and more reflux symptoms compared with PD. Change on LES function after treatment may explain the outcome in part. Type I achalasia may respond better to therapies compared with type II.


2017 ◽  
Vol 6 (2) ◽  
pp. 106 ◽  
Author(s):  
Yuan Yu ◽  
Dhiman Bhadra ◽  
Balgobin Nandram

Fisher's exact test is commonly used for testing the hypothesis of independence between the row and column variables in a $r \times c$ contingency table. It is a ``small-sample'' test since it is used when the sample size is not large enough for the Pearsonian chi-square test to be valid. Fisher's exact test conditions on both margins of a $2 \times 2$ table leading to a hypergeometric distribution of the cell counts under independence. Moreover, it is conservative in the sense that its actual significance level falls short of the nominal level. In this paper, we modify Fisher's exact test by lifting the restriction of fixed margins and allow the margins to be random. In doing so, we propose two new tests - a likelihood ratio test in a frequentist framework and a Bayes factor test in a Bayesian framework, both of which are based on a new multinomial distributional framework. We apply the three tests on data from the Worcester Heart Attack study and compare their power functions in assessing gender difference in the therapeutic management of patients with acute myocardial infarction (AMI).


Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 2747-2747
Author(s):  
Chern Siang Lee ◽  
Margaret Ashton-Key ◽  
Sergio Cogliatti ◽  
Susanne Crowe ◽  
Mark S Cragg ◽  
...  

Abstract Abstract 2747 Background: Single-agent immunotherapy with rituximab is a viable treatment option for low risk FL, with limited toxicity and a long duration of response in some patient subsets. We have previously shown that high expression of FcγRIIB promotes rituximab internalisation on various B cell targets, including FL (Blood 2011 118:2530–2540), something not seen with type II anti-CD20 antibodies. The SAKK 35/98 trial examined rituximab monotherapy in FL and now has long-term follow-up data of almost 10 years (JCO 2010 28:4480–4484). We analysed diagnostic tumour samples from this trial to determine the relationship of FcγRIIB expression to responses and clinical outcomes after rituximab treatment in FL. Methods: 202 patients (pts) with newly diagnosed or relapsed FL received induction treatment with rituximab 375 mg/m2 weekly for 4 weeks. Pts with stable or responding disease at week 12 were randomized into 2 groups: no further treatment or prolonged treatment with single infusions of rituximab 375 mg/m2 at weeks 12, 20, 28 and 36. Archived tissue samples from 135 evaluable pts were stained using an anti-human FcγRIIB antibody (clone EP888Y, Abcam) at a dilution of 1:3000 on a Dako autostainer. The samples were pretreated with the Dako EnVisionFLEX target retrieval solution high pH and detection using the Dako AS-Link 48 with Dako EnVision flex plus detection kit. Positive samples were graded into negative/low intensity staining (n=120) versus medium/high (n=13) by an expert lymphoma histopathologist blinded to the clinical outcomes. Data from 2 slides and response at week 12 data for 4 pts were unavailable (1 of whom also has missing slide data), resulting in 130 pts available for analysis. Failure-free survival (FFS) was defined as time from registration until failure to achieve complete/partial response at week 12, progression, relapse, a second cancer or death from any cause. Objective response rate (ORR) was associated with intensity staining levels using Fisher's exact test. All time-to-event endpoints were evaluated using the Kaplan-Meier method; groups were compared using the log-rank test. The hazard ratio (HR) was assessed using Cox proportional hazards models. Results: Registered and randomised pts had very similar baseline characteristics; previously untreated pts had slightly more favourable characteristics but were balanced between the 2 treatment arms. Pts expressing medium/high levels of FcγRIIB were less likely to respond to rituximab by week 12 (ORR 58.1% vs 23.1%, Fisher's exact test, p=0. 02), a finding independent of prior therapy. For FFS, there was a statistically significant difference (p=0.001; HR=0.42; 95% confidence interval (C.I.): 0.23–0.77) between the negative/low staining group (median: 21.4 months; 95% C.I.: 7.0–34.2) and the medium/high staining group (median: 7.0 months; 95% C.I.: Not calculable). The interaction between staining levels and randomised treatment groups for FFS was not statistically significant. There was a non-significant trend towards better overall survival in the low/negative group (median: 140.0 vs 50.0 months; p=0.15; HR=0.57; 95% C.I.: 0.27–1.23); however the event rate was lower (36.8% vs 61.5%). Conclusion: Elevated FcγRIIB expression level is associated with poor response to rituximab in pts with FL. This group may show better results with non-internalising type II antibodies, a hypothesis for validation in future prospective clinical trials. Disclosures: Ghielmini: Roche: Honoraria, Speakers Bureau. Johnson:Roche: Honoraria.


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