Is long-term screening for lung cancer justified in patients with head and neck carcinoma?

OBJECTIVE: Patients with head and neck squamous cell carcinoma (HNSCC) have a higher risk of second lung neoplasms than the general population. The aim of the present study is to evaluate the long-term incidence of second lung malignancies after the diagnosis of a HNSCC and to consider the convenience of the screening for lung cancer in these patients. MATERIAL AND METHODS: We conducted a retrospective study performed on 4954 patients with an index tumor located in the oral cavity, oropharynx, hypopharynx, or larynx during the period 1985-2017. RESULTS: During the follow-up period 469 patients (9.5%) presented a second pulmonary neoplasm. The incidence of second lung neoplasm was 1.26% per year and remained practically constant throughout the 25-year follow-up period analyzed. According to the results of a multivariate study, male patients, aged between 50 and 80 years, with a history of tobacco use, and with tumors located in the oropharynx or the supraglottis were those with the highest risk of second lung neoplasms. CONCLUSION: Patients with a HNSCC index tumor have a high risk of second neoplasms located in the lung. In order to achieve an early diagnosis of these second neoplasms, it would be advisable to establish screening protocols based on the use of low-dose lung CT, which should be maintained indefinitely during the follow-up period.

Case report: De novo pathogenic variant in WFS1 causes Wolfram-like syndrome debuting with congenital bilateral deafness.

Background: Congenital deafness could be the first manifestation of a syndrome such as in Usher, Pendred, and Wolfram syndromes. Therefore, a genetic study is crucial in this deficiency to significantly improve its diagnostic efficiency, to predict the prognosis, to select the most adequate treatment required, and to anticipate the development of other associated clinical manifestations. Case presentation: We describe a young girl with bilateral congenital profound deafness, who initially received a single cochlear implant. The genetic study of her DNA using a custom-designed next-generation sequencing (NGS) panel detected a de novo pathogenic heterozygous variant in the WFS1 gene related to Wolfram-like syndrome, which is characterized by the presence of other symptoms such as optic atrophy. Due to this diagnosis, a second implant was placed after the optic atrophy onset. The speech audiometric results obtained with both implants indicate that this work successfully allows the patient to develop normal speech. Deterioration of the auditory nerves has not been observed. Conclusion: The next-generation sequencing technique allows a precise molecular diagnosis of diseases with high genetic heterogeneity, such as hereditary deafness, while this was the only symptom presented by the patient at the time of analysis. The NGS panel, in which genes responsible for both syndromic and non-syndromic hereditary deafness were included, was essential to reach the diagnosis in such a young patient. Early detection of the pathogenic variant in the WFS1 gene allowed us to anticipate the natural evolution of the disease and offer the most appropriate management to the patient.

Relationship between the transcriptional expression of PIM1 and local control in patients with head and neck squamous cell carcinomas treated with radiotherapy.

PURPOSE: Proviral integration site for Moloney murine leukemia virus (PIMs) are proto-oncogenes encoding serine/threonine kinases that phosphorylate a variety of substrates involved in the regulation of cellular processes. Elevated expression of PIM-1 has been associated with poor prognosis in several types of cancer. There are no studies that have analyzed the response to radiotherapy in patients with head and neck squamous cell carcinoma (HNSCC) according to the expression of PIM-1. The aim of our study was to analyze the relationship between the transcriptional expression of PIM-1 and local response to radiotherapy in HNSCC patients. METHODS: We determined the transcriptional expression of PIM-1 in 135 HNSCC patients treated with radiotherapy, including patients treated with chemoradiotherapy (n = 65) and bioradiotherapy (n = 15). RESULTS: During the follow-up, 48 patients (35.6%) had a local recurrence of the tumor. Patients with local recurrence had a higher level of PIM-1 expression than those who achieved local control of the disease (P = 0.017). Five-year local recurrence-free survival for patients with a high expression of PIM-1 (n = 43) was 44.6% (95% CI 29.2-60.0%), and for patients with low expression (n = 92) it was 71.9% (95% CI 62.5-81.3%) (P = 0.007). According to the results of multivariate analysis, patients with a high PIM-1 expression had a 2.2-fold increased risk of local recurrence (95% CI 1.22-4.10, P = 0.009). CONCLUSION: Patients with elevated transcriptional expression levels of PIM-1 had a significantly higher risk of local recurrence after radiotherapy.

Prognostic significance of extranodal extension in head and neck squamous cell carcinoma cN0 patients with occult metastatic neck nodes. / Significado pronóstico de la extensión extranodal en pacientes con carcinomas escamosos de cabeza y cuello cN0 con metástasis ganglionares ocultas.

INTRODUCTION AND OBJECTIVES: Extranodal extension in nodal metastases is an independent adverse prognostic factor in head and neck squamous cell carcinoma patients. However, few studies specifically address the subgroup of patients with no clinical evidence of nodal disease. MATERIAL AND METHODS: We retrospectively analysed data from 348 head and neck squamous cell carcinoma patients without any previous treatment and lacking clinical or radiological evidence of neck node metastases during the initial workup, treated with an elective neck dissection between 1992-2014. The incidence of occult metastatic neck nodes with extranodal extension and the impact of extranodal extension in survival were evaluated. RESULTS: The proportion of patients with occult neck node metastases was 33%. Of these, 23.5% had at least one metastatic neck node with extranodal extension. There were significant differences in the disease-specific survival rate according to neck node status. Five-year disease-specific survival for patients without histopathological metastases was 90%, for patients with occult neck node metastases without extranodal extension it was 71.2%, and for patients with occult neck node metastases with extranodal extension it was 25.9% (P=.0001). The multivariate analysis revealed that the presence of occult node metastases with extranodal extension was the factor with strongest impact on survival. The inclusion of the extranodal extension as a criterion of histopathological evaluation in the 8th TNM classification edition improves the prognostic capacity compared to previous TNM editions. CONCLUSIONS: Appearance of metastatic neck nodes with extranodal extension is an adverse prognostic factor in head and neck squamous cell carcinoma patients without clinical evidence of regional disease during the initial workup of the tumour.

Prognostic significance of extracapsular spread in isolated neck recurrences in head and neck squamous cell carcinoma patients.

Few studies have analyzed the appearance of extracapsular spread (ECS) in salvage neck dissections carried out after regional recurrence of the disease. The aim of our study was to evaluate the frequency of ECS in patients with an isolated regional recurrence treated with a salvage neck dissection, and to assess the influence of ECS on prognosis. We conducted a retrospective study of 123 patients treated with a salvage neck dissection. Eighty-two patients (66.7 %) had nodes with ECS. Five-year salvage-specific survival for patients without ECS was 77.2 %, whereas for patients with ECS it was 32.0 % (P = 0.0001). According to the results of a multivariate analysis, the presence of ECS in the salvage neck dissection was the only variable significantly related to the salvage-specific survival. Sixty-six percent of the patients with nodes with ECS had adjuvant treatment with radiotherapy or chemoradiotherapy. Five-year salvage-specific survival for patients with ECS who had not received adjuvant treatment (n = 26) was 15.2 %, whereas for patients treated with adjuvant radiotherapy (n = 39) or chemotherapy (n = 17), 5-year salvage-specific survival was 36.4 and 47.1 %, respectively. Patients with ECS could benefit from adjuvant treatment with radiotherapy or chemoradiotherapy.

Influence of vitamin D status on the effect of statins on bone mineral density and bone turnover markers in postmenopausal women.

OBJECTIVE: This study sought to assess whether the association between statin use and bone mineral density (BMD) and bone turnover markers is modulated by serum 25-hydroxyvitamin D (25OHD) levels in postmenopausal women. Design, Participants, and Settings: Approximately 1422 postmenopausal women were recruited from the Camargo Cohort after excluding those with any known medical disorder or drug that might affect bone metabolism. Participants were categorized into four groups: 25OHD levels of 20 ng/mL or less and not taking statins (group 1; n = 492); 25OHD levels greater than 20 ng/mL and on statins (group 2; n = 143); 25OHD levels of 20 ng/mL or less and using statins (group 3; n = 112); and 2OHD levels greater than 20 ng/mL and non-statin use (group 4; n = 675). Multivariate analyses were performed to compare BMD and bone turnover markers between groups. RESULTS: Women in group 2 had an adjusted femoral neck and total hip BMD higher than women in group 1 (P < .0001 and P = .003, respectively). A trend toward a significant difference was observed regarding lumbar BMD (P = .08). Serum aminoterminal propeptide of type 1 collagen and C-terminal telopeptide of type 1 collagen levels were lower in group 2 than in group 1, in crude and adjusted models, although only serum C-terminal telopeptide of type 1 collagen difference was significant (P = .009). CONCLUSIONS: Women on statins and serum 25OHD levels above 20 ng/mL have greater BMD and less bone resorption than those without either of the factors. Differences, however, are not significant in women with only one of them. Vitamin D and statins seem to interact positively in their effects on bone metabolism.

Inclusion of extracapsular spread in the pTNM classification system: a proposal for patients with head and neck carcinoma.

IMPORTANCE: The inclusion of data about the presence of metastatic neck nodes with extracapsular spread (ECS) in the neck dissection improves the prognostic classification of patients with head and neck squamous cell carcinoma (HNSCC). OBJECTIVE: To evaluate the prognostic capacity of ECS in patients with HNSCC, and to analyze the usefulness of including this information in the pathological classification of patients treated with a neck dissection. DESIGN: Retrospective unicenter study performed from 1985 through 2007. SETTING: Tertiary referral center. PARTICIPANTS: A total of 1190 patients with HNSCC treated with a neck dissection. INTERVENTION: Unilateral or bilateral neck dissection . MAIN OUTCOMES AND MEASURES: Adjusted survival and local, regional, and distant metastases-free survival. Patients were classified according to a recursive partitioning analysis (RPA) method, considering pN category and number of neck nodes with ECS as the independent variables. RESULTS: Five-year adjusted survival for patients without metastatic nodes in the neck dissection (pN0) was 85.5%, for patients with neck node metastases without ECS (pN+/ECS-) it was 62.5%, and for patients with neck node metastases with ECS (pN+/ECS+) it was 29.9%. There were significant differences in survival between patients with pN0 lesions and pN+/ECS- (P < .001), and between patients with pN+/ECS- and those with pN+/ECS+ (P < .001). According to the RPA method, we propose classifying patients according to 4 categories: category I, pN0 lesions; category II, pN1/ECS+ or pN+/ECS-; category III, pN2-3/1 node and ECS+; and category IV, pN2-3/2 or more nodes and ECS+. The RPA-derived classification achieved a better prognostic discrimination than the pTNM classification. CONCLUSIONS AND RELEVANCE: The inclusion of information about ECS in the neck dissection improved the prognostic classification of patients with HNSCC in relation to the pTNM classification.

Heel quantitative ultrasound parameters in subjects with the metabolic syndrome: the Camargo Cohort Study.

OBJECTIVES: To compare bone parameters measured by calcaneous quantitative ultrasonography (BUS) in subjects with and without metabolic syndrome (MetS). In addition, we wanted to examine the association of each of the individual components of the syndrome with BUS measurements, to study the relationship between calciotropic hormones or bone turnover markers with BUS parameters in subjects with or without MetS, and to explore the possibility that the relationship between prevalent vertebral and non-vertebral fractures and BUS is influenced by MetS status. STUDY DESIGN: Cross-sectional study. RESULTS: We investigated 1209 (421 men and 788 women) participants from the Camargo Cohort Study. Prevalence of MetS was 27% in men and 31% in women. Women, but not men, with MetS had higher age-adjusted BUS parameters compared with those without (p<0.05), the difference disappearing after adjustment for BMI. Out of the five single components of MetS, only waist perimeter was significantly associated with BUS (p<0.01), the association being restricted to women. In men and women with MetS (but not without) a positive significant association was observed between BUS and 25OHD levels. BUS parameters were associated with serum P1NP or CTX in normal women, but not in those with MetS. Prevalent vertebral and non-vertebral fractures and BUS parameters (BUA and SOS, respectively) are inversely associated, but this relationship, however, is not influenced by MetS status. CONCLUSIONS: BUS parameters are higher in women with MetS, and this difference disappears after adjusting for BMI. MetS status did not influence the relationship between BUS parameters and vertebral or non-vertebral fractures.

Management of sinonasal inverted papillomas and comparison of classification staging systems.

BACKGROUND: The aim of this study was to describe treatment results in patients with sinonasal inverted papilloma and to compare recent classification staging systems. METHODS: We performed a retrospective study of 79 patients with primary paranasal sinus inverted papilloma from 1978 to 2008. RESULTS: The median age at diagnosis was 59 years. There were 68 men (86%) and 11 women (14%). Sixty inverted papilloma (76%) were located in the ethmoidal sinus complex, 16 (20%) were in the maxillary sinus, 2 were in the sphenoid sinus (3%), and 1 was in the septum (1%). Malignancy was simultaneously associated in four cases (5%). Intracranial extension was found in five patients (6%) and we did not find orbital content involvement. The external approach was used in 22 cases (28%) and 57 patients were treated with endoscopic nasal resection (72%). The overall recurrence rate in the total population was 21%. Recurrences were observed in 7 cases (32%) in the group of patients who received external approach and in 10 (17%) patients in the endoscopic group. Recurrences according to the Krouse system were 0% in T1 stage, 16% in T2 stage, 25% in T3 stage, and 60% in T4 stage (p = 0.05). Recurrences for groups A, B, and C stages using the Cannady staging system were 12, 26, and 60%, respectively (p = 0.039). Recurrences according to Han's system were 19% in both T1 and T2, 20% in T3, and 60% in T4 (p > 0.05). CONCLUSION: Our results support the endoscopic approach as the treatment of choice when feasible in patients with inverted papilloma, combined in selected cases with external approaches. The Krouse and Cannady systems provided a good distribution of patients according to local control.

Serum lipids and bone metabolism in Spanish men: the Camargo cohort study.

There is growing evidence of a link between lipid and bone metabolism, although data on this association in European men are scarce. This cross-sectional study from a community-based prospective cohort aims to explore the association of serum lipids with different aspects of bone metabolism in Spanish men. Demographic and anthropometric measurements, biochemical parameters including serum lipids, bone remodelling markers and calciotropic hormones, bone mineral density (BMD) assessed by dual X-ray absorptiometry and heel quantitative ultrasound, and prevalent vertebral and non-vertebral fractures, were evaluated in 289 men. Calciotropic hormones or bone markers were not associated with serum lipids. Serum total (TC) and LDL cholesterol, as well as LDL/HDL ratio were positively correlated to BMD at lumbar spine and hip. No significant correlation was noted for triglycerides or HDL. We observed a positive association between triglycerides, LDL/HDL ratio and BUA, and between TC/HDL ratio and both, QUI and BUA. BMD at the femoral neck and total hip was significantly higher in men with hypercholesterolemia after controlling for all the covariates (p=0.007). We did not observe any association between serum lipids and prevalent vertebral fractures. However, we found that TC (p=0.03) and LDL (p=0.04) were lower in subjects with non-vertebral fractures. In conclusion, we have found that a more unfavorable lipid profile (mainly higher LDL-C levels) is associated with higher BMD at lumbar spine and hip in Spanish men. Moreover, we did not observe any association between hypercholesterolemia and prevalent vertebral fractures, but we found lower serum TC and LDL-C levels in men with prevalent non-vertebral fractures.