Elective neck dissection in patients with head and neck adenoid cystic carcinoma: an international collaborative study.

BACKGROUND: Adenoid cystic carcinoma (ACC) accounts for 3-5 % of all head and neck malignancies. Investigations of outcomes from elective neck dissection (END) for patients with ACC are sparse. This study aimed to assess the impact of END on the survival of patients with ACC. METHODS: This retrospective multicentered study investigated 270 patients who underwent neck dissection. A multivariate analysis assessed associations of clinical and histopathologic characteristics with survival outcomes. RESULTS: The primary tumor sites included the oral cavity in 250 patients (55 %), the major salivary glands in 133 patients (29 %), the sinonasal mucosa in 68 patients (15 %), and the larynx in six patients (1 %). The overall rate of occult nodal metastases among the patients who underwent END was 17 % (38/226). The highest incidence of occult nodal metastases was with the oral cavity (66 %). The 5-year overall survival (72 and 79 % for patients with or without END, respectively) and disease-specific survival (74 and 81 % for patients with or without END, respectively) were similar in the two groups. The subgroup analysis of patients according to the primary site showed no significant impact of END on outcome. In the multivariate analysis, primary site, T classification, and N classification were the only variables associated with outcome. CONCLUSIONS: The incidence of occult neck metastases among patients with ACC is 17 %. The highest incidence of occult metastases is with the oral cavity. Statistical analysis showed no survival advantage for patients who underwent END compared with those who did not.

Association of in vitro fertilization outcome with circulating insulin-like growth factor components prior to cycle initiation.

OBJECTIVE: Components of the insulin-like growth factor (IGF) system enhance in vitro embryo quality and implantation rates in both animal models and human in vitro fertilization (IVF). We evaluated whether differences in serum levels of these components in women prior to initiation of an IVF cycle would be predictive of subsequent outcome. STUDY DESIGN: In this retrospective study sera from women obtained at day 2 of their IVF cycle (at baseline before stimulation) were assayed for IGF-I, IGF-II, and IGF binding protein (BP)-1 by enzyme-linked immunosorbent assay. Samples from 54 women with a live birth, 38 with a transient biochemical pregnancy, 45 with a spontaneous abortion, 54 who did not become pregnant, and 35 who had an ectopic pregnancy were available for analysis. Associations between the assays and outcome were evaluated by the Kruskal-Wallis test and receiver operating characteristic analysis. RESULTS: There were no differences in the number of oocytes retrieved, oocyte quality, fertilization rates, or embryo grade between groups. Median concentrations of IGF-I were elevated in women with a live birth (29.1 ng/mL) as compared to women with a biochemical pregnancy (25.6 ng/mL), with spontaneous abortion (21.2 ng/mL), who were not pregnant (18.7 pg/mL), or who had an ectopic pregnancy (4.2 pg/mL) (P < .001). Conversely, median levels of IGF-II were reduced in women with a live birth (294.5 ng/mL) as opposed to 357.5, 393.6, 407.2, and 426.9 ng/mL in women with a biochemical pregnancy, with ectopic pregnancy, with spontaneous abortion, or who were not pregnant, respectively (P < .001). Median IGFBP-1 concentrations were markedly elevated in women with a live birth (23.6 ng/mL) compared to 18.3, 14.1, 13.8, and 9.5 ng/mL in women with a biochemical pregnancy, with spontaneous abortion, who were not pregnant, or with an ectopic pregnancy (P < .001). The combination of IGF-I and IGFBP-1 best predicted the occurrence of a live birth with an area under the curve of 0.892. CONCLUSION: Maternal serum levels of IGF-I, IGF-II, and IGFBP-1 prior to initiation of an IVF cycle are correlated with the likelihood of a live birth. Alterations in maternal IGF system components may influence oocyte quality or the success of early postfertilization events and embryo implantation.

Reduced Circulating Concentration of Brain-derived Neurotrophic Factor is Associated with Peri- and Post-implantation Failure following In Vitro Fertilization-Embryo Transfer.

PROBLEM: We evaluated associations between brain-derived neurotrophic factor (BDNF) and neurotrophin-4 (NT4) and pregnancy outcome in women undergoing in vitro fertilization-embryo transfer (IVF-ET). METHOD OF STUDY: Sera obtained on days 24 and 28 of an IVF cycle from women with a live birth, spontaneous abortion, biochemical pregnancy, not pregnant, or an ectopic pregnancy were retrospectively analyzed for BDNF and NT4 by ELISA. RESULTS: Median BDNF levels were higher in women with a live birth compared to women with an ectopic pregnancy (P < 0.0001), spontaneous abortion (P < 0.0001), or a biochemical pregnancy (P = 0.0004), but not in women who did not become pregnant. NT4 was detected in <25% of sera and did not differ by outcome. There was no association between BDNF level and oocyte or pre-transfer embryo parameters. CONCLUSION: Decreased circulating BDNF early in an IVF cycle is associated with adverse peri- and/or post-implantation events and subsequent pregnancy failure.

The serum brain-derived neurotrophic factor concentration prior to initiation of an in vitro fertilization cycle predicts outcome.

Our objective was to determine if the concentration of circulating brain-derived neurotrophic factor (BDNF) prior to cycle initiation predicts outcome in women undergoing in vitro fertilization (IVF). Stored serum samples from 226 women - 54 with a live birth, 45 with a spontaneous abortion, 38 with a biochemical pregnancy, 54 who did not become pregnant and 35 with an ectopic pregnancy- were retrospectively blindly tested for BDNF by ELISA. The median serum concentration of BDNF was highest in women with an extrauterine ectopic pregnancy (7.3ng/ml), intermediate in women whose embryos did not implant (5.5ng/ml) and lowest in women with a spontaneous abortion (4.2ng/ml), biochemical pregnancy (3.8ng/ml) or a live birth (3.6ng/ml) (P<0.0001). Among women with a positive pregnancy test an elevated BDNF level predicted an ectopic pregnancy with a sensitivity of 0.853 (0.689, 0.950) and a specificity of 0.949 (0.897, 0.979). We conclude that elevated BDNF in serum obtained before IVF cycle initiation is predictive of an extrauterine pregnancy.

Racial disparities in incidence of human papillomavirus-associated oropharyngeal cancer in an urban population.

BACKGROUND: Recent studies suggest that rates of human papillomavirus related oropharyngeal cancer (HPVOPC) in the US are higher in Caucasians than minorities. We hypothesized that this disparity would be less marked in a racially and ethnically diverse population from New York City. METHODS: This is a retrospective chart review of 210 patients with biopsied or surgically treated OPC at the Icahn School of Medicine at Mount Sinai (ISMMS) between 1999 and 2013. Polymerase chain reaction (PCR) was used to detect the presence of HPV-DNA in paraffin-embedded tumor blocks. Incidence of HPV-positive cancers was compared between Caucasians and minorities (defined as African Americans, Asians, and Hispanics) using Fisher's exact test. RESULTS: We found a higher incidence of HPV-positive OPC in Caucasians than racial minorities within the ISMMS population (p=0.002). HPV incidence detected by PCR was 139/165 [84.2%] for Caucasians and 28/45 [62.2%] for minorities. Specifically, there was a higher rate in Caucasians compared to African Americans (p=0.017), but no significant difference between Caucasians and Hispanics (p=0.087). CONCLUSION: We documented a disparity in incidence of HPVOPC amongst racial groups, consistent with previously reported trends from study populations in less urbanized areas. Thus we conclude that the factors underlying racial/ethnic disparities in HPVOPC incidence are likely to be similar across communities with different levels of urbanization and population diversity.

Risk of Second Primary Tumors After Childhood and Adolescent Ovarian Malignancies: A SEER Analysis (1973-2011).

STUDY OBJECTIVE: To calculate the incidence of second primary tumors (SPTs) in patients previously diagnosed with malignant ovarian tumors in childhood and adolescence. This is an area of interest given the high survival rate and, thus, the long disease-free period that these patients face. DESIGN AND PARTICIPANTS: We conducted a retrospective study following a cohort of patients between 1973 and 2011. Using the National Cancer Institute's Surveillance, Epidemiology and End-Result (SEER) database, we identified patients with an ovarian malignant tumor diagnosed at 19 years of age or younger. RESULTS: Of the 806 patients included in our study, 28 patients developed an SPT after the diagnosis of malignant ovarian tumor. This cohort had higher risk of solid tumors (standardized incidence ratio [SIR] 1.85, 95% CI 1.15 to 2.83) and lymphohematologic malignancies (SIR 5.28, 95% CI 2.12 to 10.88) compared with the general population. There is a higher incidence of lymphoma (SIR 4.25, 95% CI 1.16 to 10.89) and acute nonlymphocytic leukemia (SIR 19.65, 95% CI 4.05 to 57.42), following initial diagnosis of ovarian malignancy during childhood or adolescence. CONCLUSION: The association between ovarian malignancy during childhood or adolescence and lymphoma has not been previously described. Increased incidence of acute nonlymphocytic leukemia supports previous data, underlying the need for long-term follow-up and surveillance of these patients.

Interaction between the inducible 70-kDa heat shock protein and autophagy: effects on fertility and pregnancy.

A consequence of hsp70 (HSPA1A) induction is the inhibition of autophagy. Evidence of autophagy involvement in all aspects of the reproductive process is reviewed, and possible consequences of hsp70 induction at each developmental stage are postulated. It is proposed that aberrant external or internal stimuli that result in high levels of hsp70 production interfere with normal autophagy-related functions and lead to a decrease in the number of functional ova and spermatozoa, impaired pre- and post-implantation embryo development, and increased susceptibility to premature labor and delivery. The purpose of this review is to increase understanding of hsp70-autophagy interactions during reproduction. Interventions to modulate this interaction will lead to development of novel protocols to improve fertility and pregnancy outcome.

Predictive biomarkers of preterm delivery in women with ongoing IVF pregnancies.

In vitro fertilization (IVF) pregnancies potentially have a higher rate of preterm delivery (PTD) than do spontaneously conceived gestations, and differences persist following adjustment for multiple gestation, maternal age, and parity. The reasons for this increased susceptibility to PTD remain incompletely elucidated. To identify potential biomarkers predictive of PTD in IVF subjects, we performed a retrospective analysis of multiple markers in sera obtained during early gestation that have been suggested to be associated with peri-implantation events. Sera from 35 women with a preterm birth and 68 women with a term delivery, obtained between 9 and 11 days after embryo transfer, were tested blindly for concentrations of interleukin (IL)-1ß, IL-6, IL-13, IL-17, human epididymal protein 4 (HE4), secretory leukocyte protease inhibitor (SLPI), insulin-like growth factor (IGF)-I, IGF-II, IGF binding protein (BP)-1, and interferon-γ. Concentrations of HE4 (p=0.001) and IL-13 (p=0.029) were reduced, and levels of IGF-II (p=0.023) and SLPI (p=0.043) were increased, in women who subsequently delivered preterm. By receiver operator curve analysis, the combination of HE4 and IL-13 levels best predicted the outcome preterm birth. The association between deficiencies in circulating HE4 and IL-13 levels during early pregnancy and subsequent PTD suggest that factors contributing to sub-optimal embryo implantation influence length of gestation in women undergoing IVF.

Incidence of cervical lymph node metastasis and its association with outcomes in patients with adenoid cystic carcinoma. An international collaborative study.

BACKGROUND: The patterns of regional metastasis in adenoid cystic carcinoma (ACC) of the head and neck and its association with outcome is not established. METHODS: We conducted a retrospective multicentered multivariate analysis of 270 patients who underwent neck dissection. RESULTS: The incidence rate of neck metastases was 29%. The rate observed in the oral cavity is 37%, and in the major salivary glands is 19% (p = .001). The rate of occult nodal metastases was 17%. Overall 5-year survival rates were 44% in patients undergoing therapeutic neck dissections, and 65% and 73% among those undergoing elective neck dissections, with and without nodal metastases, respectively (p = .017). Multivariate analysis revealed that the primary site, nodal classification, and margin status were independent predictors of survival. CONCLUSION: Our findings support the consideration of elective neck treatment in patients with ACC of the oral cavity.

International collaborative validation of intraneural invasion as a prognostic marker in adenoid cystic carcinoma of the head and neck.

BACKGROUND: The purpose of this study was to characterize the incidence, pattern of spread, and prognostic correlation of nerve invasion in patients with adenoid cystic carcinoma (ACC). METHODS: Using 3 different pathological categories of perineural invasion, intraneural invasion, and perineural inflammation, we investigated the prognostic value of nerve invasion in a total of 495 ACCs from 9 international patient cohorts with median follow-up 90 months (range, 12-288 months). RESULTS: Of 239 patients (48%) with nerve invasion, 174 (73%) had perineural invasion, 65 (27%) intraneural invasion, and 37 (15%) perineural inflammation. Multivariate Cox regression analysis identified tumor site (p = .008; hazard ratio [HR] = 1.8; 95% confidence interval [CI] = 0.07-3.7) and intraneural invasion (p < .001; HR = 5.9; 95% CI = 0.8-12.3) as independent prognostic markers for both overall survival (OS) and disease-specific survival (DSS), but not of distant metastases. CONCLUSION: Although perineural invasion has no impact on survival, intraneural invasion is an independent predictor of poor prognosis. Recognition of intraneural invasion may help optimize treatment of patients with head and neck ACC.

Analysis of failure in patients with adenoid cystic carcinoma of the head and neck. An international collaborative study.

BACKGROUND: Adenoid cystic carcinoma (ACC) is a locally aggressive tumor with a high prevalence of distant metastases. The purpose of this study was to identify independent predictors of outcome and to characterize the patterns of failure. METHODS: An international retrospective review was conducted of 489 patients with ACC treated between 1985 and 2011 in 9 cancer centers worldwide. RESULTS: Five-year overall-survival (OS), disease-specific survival (DSS), and disease-free survival (DFS) were 76%, 80%, and 68%, respectively. Independent predictors of OS and DSS were: age, site, N classification, and presence of distant metastases. N classification, age, and bone invasion were associated with DFS on multivariate analysis. Age, tumor site, orbital invasion, and N classification were independent predictors of distant metastases. CONCLUSION: The clinical course of ACC is slow but persistent. Paranasal sinus origin is associated with the lowest distant metastases rate but with the poorest outcome. These prognostic estimates should be considered when tailoring treatment for patients with ACC.

Adenoid cystic carcinoma of the nasal cavity and paranasal sinuses: a meta-analysis.

Objectives To identify independent predictors of outcome in patients with adenoid cystic carcinoma (ACC) of the paranasal sinuses and skull base. Design Meta-analysis of the literature and data from the International ACC Study Group. Setting University-affiliated medical center. Participants The study group consisted of 520 patients, 99 of them from the international cohort. The median follow-up period was 60 months (range, 32 to 100 months). Main Outcome Measures Overall survival (OS) and disease-specific survival (DSS). Results The 5-year OS and DSS of the entire cohort were 62% and 67%, respectively. The local recurrence rate was 36.6%, and the regional recurrence rate was 7%. Distant metastasis, most commonly present in the lung, was recorded in 106 patients (29.1%). In the international cohort, positive margins and ACC of the sphenoid or ethmoidal sinuses were significant predictors of outcome (p < 0.001). Perineural invasion and adjuvant treatment (radiotherapy or chemoradiation) were not associated with prognosis. Conclusion Tumor margin status and tumor site are associated with prognosis in ACC of the paranasal sinuses, whereas perineural invasion is not. Adjuvant treatment apparently has no impact on outcome.