Prognostic value of the nodal yield in elective neck dissections in patients with head and neck carcinomas.

PURPOSE: The objective of this study is to assess the prognostic capacity of the nodal yield in elective neck dissections performed in patients with head and neck squamous cell carcinomas (HNSCC) without clinical or radiological evidence of regional involvement (cN0) at the time of diagnosis. METHODS: Retrospective study including 647 patients with HNSCC treated with an elective neck dissection. RESULTS: Patients with < 15 dissected nodes (n = 172, 26.6%) had a 5-year disease-specific survival of 64.9% (95% CI: 57.3-72.5%), while for patients with ≥ 15 dissected nodes (n = 475, 73.4%), it was of 81.9% (95% CI: 78.4-85.4%) (P = 0.0001). The nodal yield category had prognostic capacity on the disease-specific survival in patients with tumors located in the oral cavity (P = 0.001), the oropharynx (P = 0.023) and the hypopharynx (P = 0.034), while for patients with tumors located in the larynx, no significant differences appeared (P = 0.779). Differences in regional recurrence-free survival were also observed based on the nodal yield category in patients with extra-laryngeal tumors (5-year regional recurrence-free survival of 81.0% in patients with < 15 dissected nodes vs 89.0% in patients with ≥ 15 dissected nodes; P = 0.046). CONCLUSION: The nodal yield in elective neck dissections in patients without evidence of lymph node disease (cN0) had prognostic capacity depending on the location of the primary tumor. For tumors located in the larynx, the number of dissected nodes did not significantly influence the prognosis. For tumors located in the oral cavity, oropharynx or hypopharynx, patients with < 15 dissected nodes had a disease-specific mortality 2.9 times higher than patients with ≥ 15 dissected nodes.

Causes of long-term mortality in patients with head and neck squamous cell carcinomas.

PURPOSE: After treatment of a head and neck squamous cell carcinoma (HNSCC), patients with an adequate control of the tumor have a decreased overall survival when compared to age- and gender-matched controls in the general population. The aim of our study was to analyze the causes of long-term mortality in patients with HNSCC. METHODS: We carried out a retrospective study of 5122 patients with an index HNSCC treated at our center between 1985 and 2018. We analyzed the survival considering three causes of death: mortality associated with the HNSCC index tumor, mortality associated with a second or successive neoplasm, and mortality associated with a non-cancer cause. RESULTS: After the diagnosis of an HNSCC the most frequent cause of death is the head and neck tumor itself during the first 3.5 years of follow-up. Thereafter, mortality is more frequently associated with competing causes of death, such as second malignancies and non-cancer causes. Mortality associated with second and successive neoplasms was 2.3% per year, a percentage that was maintained constant throughout the follow-up. Likewise, mortality attributable to non-cancer causes was 1.6% per year, which also remained constant. There were differences in the mortality patterns according to the characteristics of the patients. CONCLUSION: There are differences in the mortality patterns of patients with HNSCC depending on their characteristics. Knowledge of these patterns can help in the design of guidelines to improve the follow-up protocols of this group of patients to optimize the clinical cost-effectiveness.

Clinical and Genetic Features of Autosomal Dominant Alport Syndrome: A Cohort Study.

RATIONALE & OBJECTIVE: Alport syndrome is a common genetic kidney disease accounting for approximately 2% of patients receiving kidney replacement therapy (KRT). It is caused by pathogenic variants in the gene COL4A3, COL4A4, or COL4A5. The aim of this study was to evaluate the clinical and genetic spectrum of patients with autosomal dominant Alport syndrome (ADAS). STUDY DESIGN: Retrospective cohort study. SETTING & PARTICIPANTS: 82 families (252 patients) with ADAS were studied. Clinical, genetic, laboratory, and pathology data were collected. OBSERVATIONS: A pathogenic DNA variant in COL4A3 was identified in 107 patients (35 families), whereas 133 harbored a pathogenic variant in COL4A4 (43 families). Digenic/complex inheritance was observed in 12 patients. Overall, the median kidney survival was 67 (95% CI, 58-73) years, without significant differences across sex (P=0.8), causative genes (P=0.6), or type of variant (P=0.9). Microhematuria was the most common kidney manifestation (92.1%), and extrarenal features were rare. Findings on kidney biopsies ranged from normal to focal segmental glomerulosclerosis. The slope of estimated glomerular filtration rate change was-1.46 (-1.66 to-1.26) mL/min/1.73m2 per year for the overall group, with no significant differences between ADAS genes (P=0.2). LIMITATIONS: The relatively small size of this series from a single country, potentially limiting generalizability. CONCLUSIONS: Patients with ADAS have a wide spectrum of clinical presentations, ranging from asymptomatic to kidney failure, a pattern not clearly related to the causative gene or type of variant. The diversity of ADAS phenotypes contributes to its underdiagnosis in clinical practice.

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.

The aspartate aminotransaminase/alanine aminotransaminase (De Ritis) ratio predicts sensitivity to radiotherapy in head and neck carcinoma patients.

BACKGROUND: The aim of this study is to evaluate the relationship between the aspartate aminotransaminase (AST) and alanine aminotransaminase (ALT) ratio and local disease control in patients with head and neck squamous cell carcinomas (HNSCC) treated with radiotherapy/chemoradiotherapy. METHODS: We calculated the pre-treatment AST/ALT ratio in 670 patients with HNSCC treated with radiotherapy (n = 309, 46.1%) or chemoradiotherapy (n = 361, 53.9%). RESULTS: Five-year local recurrence-free survival for patients with a low AST/ALT ratio value (n = 529, 79.0%) was 75.0% (95% CI: 71.1-78.9), and for patients with a high value (n = 141, 21.0%) it was 53.4% (CI 95: 44.4-62.4) (p = 0.0001). In a multivariable analysis, patients with a high ratio had nearly twice the risk of having a local tumor recurrence (HR 1.97, 95% CI 1.42-2.75, p = 0.0001). CONCLUSION: The AST/ALT ratio was independently associated with the risk of local recurrence in patients with HNSCC treated with radiotherapy or chemoradiotherapy.

MYH9 Associated nephropathy. / Nefropatía asociada a mutación del gen MYH9.

MYH9 related diseases are caused by mutations in the MYH9 gene and constitute a rare group of genetic entities. Its inheritance follows an autosomal dominant pattern. The MYH9 gene, encodes the nonmuscle myosin heavy chain IIA, expressed in different tissues and especially in podocytes and mesangial cells. The disorder is characterized by the presence of macrothrombocytopenia, leukocyte inclusions and a variable risk of developing renal failure, hearing loss and early-onset cataracts. We describe the case of a 27-year-old Caucasian woman, diagnosed initially with idiopathic thrombocytopenic purpura. After a detailed family history and the appearance of renal involvement and hearing loss, genetic testing allowed to make the diagnosis of nephropathy associated with MYH9 mutation. This case is an example of the delayed diagnosis of uncommon diseases and highlights the usefulness genetic testing. A review of the disease is provided.

Second, third, and fourth head and neck tumors. A progressive decrease in survival.

BACKGROUND: Patients with a first head and neck carcinoma have a high risk of successive neoplasms, many of which appear again in the head and neck. Second head and neck tumors have a poorer prognosis than first tumors, but data about the prognosis of third and fourth tumors in the head and neck are lacking. METHODS: We carried out a retrospective study of 4298 patients with a primary head and neck carcinoma. Survival and the characteristics of the first tumor, second tumor, and any successive tumors in the head and neck were analyzed. RESULTS: Second and successive tumors showed a tendency to appear more frequently in the oral cavity and oropharynx and had a lower stage than that of index tumors. Five-year survival rates after a first, second, third, and fourth tumors in the head and neck were 67.6%, 56.1%, 45.0%, and 32.1%, respectively. CONCLUSION: Survival decreased progressively with every new head and neck tumor.

Nefropatía asociada a mutación del gen MYH9 / MYH9 Associated nephropathy

Las enfermedades relacionadas con mutaciones del gen MYH9 son un grupo de patologías genéticas raras. Su herencia sigue un patrón autosómico dominante en donde el gen MYH9, codifica la cadena pesada de la miosina IIA no muscular que se expresa en diferentes tejidos pero especialmente en los podocitos y en las células mesangiales. Este trastorno se caracteriza por la presencia de macrotrombocitopenia, inclusiones leucocitarias y un riesgo variable de desarrollar insuficiencia renal, hipoacusia y cataratas en edad juvenil o adulta. Describimos el caso de una mujer de 27 años, de raza caucásica, diagnosticada inicialmente de púrpura trombocitopénica idiopática. Tras una detallada historia familiar y el desarrollo de síntomas clínicos posteriores con afectación renal e hipoacusia, se le realizó un estudio genético que nos permitió el diagnóstico de nefropatía asociada a la mutación en el gen MYH9. Este caso destaca el retraso del diagnóstico y la utilidad del estudio genético en pacientes con enfermedades muy poco frecuentes. Se procede a la revisión de la enfermedad en este artículo

MYH9 related diseases are caused by mutations in the MYH9 gene and constitute a rare group of genetic entities. Its inheritance follows an autosomal dominant pattern. The MYH9 gene, encodes the nonmuscle myosin heavy chain IIA, expressed in different tissues and especially in podocytes and mesangial cells. The disorder is characterized by the presence of macrothrombocytopenia, leukocyte inclusions and a variable risk of developing renal failure, hearing loss and early-onset cataracts. We describe the case of a 27-year-old Caucasian woman, diagnosed initially with idiopathic thrombocytopenic purpura. After a detailed family history and the appearance of renal involvement and hearing loss, genetic testing allowed to make the diagnosis of nephropathy associated with MYH9 mutation. This case is an example of the delayed diagnosis of uncommon diseases and highlights the usefulness genetic testing. A review of the disease is provided