Prognostic significance of the methylation of Wnt pathway antagonists-CXXC4, DACT2, and the inhibitors of sonic hedgehog signaling-ZIC1, ZIC4, and HHIP in head and neck squamous cell carcinomas

Aberrations in Wnt and Shh signaling pathways are related to the pathogenesis of head and neck carcinomas, and their activation frequently results from epigenetic alterations. This study aimed to assess the frequency of methylation of negative regulators of Wnt signaling: CXXC4, DACT2, HDPR1, and FBXW11 and Shh signaling: HHIP, PTCH1, SUFU, ZIC1, and ZIC4 and correlate it with clinicopathological features in this group of patients.Methylation-specific PCR was used to detect gene promoter methylation, and real-time PCR was used to assess gene expression level.The analysis of the occurrence of gene promoter methylation in head and neck carcinoma cell lines indicated that CXXC4, DACT2, HHIP, ZIC1, and ZIC4 are methylated in these tumors. These genes were further analyzed in tumor sections from oral and laryngeal cancer patients. Gene methylation rate was higher in laryngeal tumors. The methylation index in tumor samples correlated with the overall survival in a subgroup of oral cancer patients who died of the disease. Moreover, ZIC4 methylation correlated with lymph node involvement in oral cancer patients.Our findings corroborate that the activation of Wnt signaling in head and neck squamous cell carcinoma (HNSCC) is related to epigenetic silencing of its negative regulators. Moreover, the results indicate that the same mechanism of activation may operate in the case of Shh signaling.The methylation of ZIC4 may be considered a new prognostic marker in oral cavity and oropharyngeal tumors. Further investigations should determine the diagnostic significance of methylation of ZIC4, HHIP, and DACT2 in head and neck carcinomas

Znaczenie postępowania pooperacyjnego w operacjach czynnościowych nosa i zatok przynosowych

Introduction. In this work we wish to emphasize the importance of postoperative care of patients who underwent FESS in ENT Department Medical University in Poznań. We feel that too little attention is still being paid to this treatment as we mostly focus on surgery. Material and methods. Our observation are based on nine year experience in functional endoscopic sinus surgery. The analysis covers patients hospitalized in our Department from January 1998 to August 2007. The schedule of postoperative care has been presented. Results. 1463 FESS operation were carried out in our Department from January 1998 to August 2007. Similar postoperative procedures were used with each patient. Full recovery of mucous membrane depended on a few parameters such as: if the patient underwent FESS for the fi rst time, what kind of changes were observed: polips or chronic infection, as well as the method of surgery (“aggressive” versus “delicate”). Healing time ranged from 6 week to 3 month. Conclusions. The scheme of procedures employed comes useful in postoperative treatment after FESS

Chirurgia endoskopowa (FESS) w przypadku jednostronnych zmian w obrębie zatok przynosowych

Wstęp: Jednostronne zmiany stanowią około 23% wszystkich przypadków stwierdzanych w obrębie nosa i zatok przynosowych. W powszechnej opinii panuje przekonanie, że są one związane głównie z rozwojem procesu nowotworowego. Dane retrospektywne z dużych ośrodków rynologicznych pokazują, że najczęściej stwierdzany jest przewlekły stan zapalny, w dalszej kolejności grzybica, brodawczak odwrócony i dopiero w niewielkim procencie przypadków zmiany złośliwe. Cel pracy: Celem pracy była analiza jednostronnych zmian zatokowych u chorych poddanych zabiegowi FESS w ośrodku drugiej referencji. Materiał i metody: Badaniem retrospektywnym objęto chorych hospitalizowanych na Oddziale Otolaryngologii Szpitala Wojewódzkiego w Poznaniu od czerwca 2014 roku do czerwca 2016 roku. Analizie poddano: wiek, płeć, lokalizację zmian, rozpoznanie histopatologiczne i mikrobiologiczne oraz przedstawiono zakres i typ postępowania chirurgicznego, jak również wyniki leczenia. Wyniki: W czasie objętym obserwacją przeprowadzono 415 operacji FESS z powodu przewlekłego zapalenia zatok. W grupie było 83 chorych leczonych z powodu jednostronnych zmian – 35 kobiet i 48 mężczyzn. W 48 przypadkach stwierdzono przewlekły stan zapalny, u 9 chorych rozpoznano grzybicę, 12 pacjentów było operowanych z powodu nowotworów niezłośliwych, takich jak brodawczak odwrócony, kostniak i guz włóknisty; u 7stwierdzono polip choanalny, 2 chorych miało ciało obce w zatoce. U 4 chorych stwierdzono hypoplastyczną zatokę szczękową, u 1 chorej – ropniak zatoki czołowej. Jednostronne otwarcie wszystkich zatok zastosowano u pacjentów z przewlekłym stanem zapalnym, endoskopową maksylektomię przyśrodkową u chorych z brodawczakiem odwróconym, izolowane otwarcie zatoki w przypadku zmian o charakterze grzybiczym. Wnioski: W przypadku jednostronnych zmian zawsze trzeba rozważyć podejrzane o rozrost nowotworowy. Technika endoskopowa z użyciem optyki kątowej pozwala na usunięcie nawet bardzo rozległych zmian zatokowych. W naszej opinii zakres operacji warunkuje charakter patologii –postępowanie rozległe wskazane jest w przypadku brodawczaka odwróconego, a ograniczone w przypadku izolowanej grzybicy

Functional endoscopic sinus surgery (FESS) in unilateral sinus disease

Background: Unilateral sinus disease (USD) occurs in 23 % of all cases. It is believed that it is mainly associated with cancer development. Retrospective data from large rhinological centers show that the most common USD is chronic rhinosinusitis (CRS), followed by mycosis, inverted papilloma and finally cancer, but only in a small percent of cases. The aim of the study: The analysis of USD in the group of patients who underwent FESS at the secondary referral center. Material and Method: The retrospective study of patients treated for USD in the Department of Otolaryngology in the Provincial Hospital in Poznan between June 2014 and June 2016. The analysis includes age, sex, the localization of lesions, histopathological and microbiological results, an extension of the surgery and treatment results. Results: Over the analyzed period of time, 415 FESS for chronic sinusitis were performed. In this group, 83 patients underwent surgery for USD. There were 35 women and 48 men.CRS was found in 48 cases, mycosis in nine cases, 12 patients were operated for non-malignant tumors, such as inverted papilloma (9), osteoma (2) and fibrosis tumor(1); seven patients had a choanal polyp and two of them had a foreign body in maxillary sinus – a tooth root lying loose. Four patients were diagnosed with a hypoplastic maxillary sinus and one patient suffered from frontal sinus pyocele. One side endoscopic opening of all sinuses was performed in the group with CRS, endoscopic medial maxillectomy was conducted in patients with inverted papilloma, and an isolated opening of the affected sinus was performed in the cases with mycosis. Conclusions: USD must be always suspected of malignant degeneration until proven otherwise. Endoscopic sinus surgery with the use of angled scope allows for the removal of even very extensive lesions. In our opinion, the extent of operation is determined by the nature of pathology. While extensive surgery is recommended in patients with inverted papilloma, a limited procedure should be performed in those with isolated mycosis

Functional endoscopic sinus surgery (FESS) in unilateral sinus disease

Background: Unilateral sinus disease (USD) occurs in 23 % of all cases. It is believed that it is mainly associated with cancer development. Retrospective data from large rhinological centers show that the most common USD is chronic rhinosinusitis (CRS), followed by mycosis, inverted papilloma and finally cancer, but only in a small percent of cases. The aim of the study: The analysis of USD in the group of patients who underwent FESS at the secondary referral center. Material and Method: The retrospective study of patients treated for USD in the Department of Otolaryngology in the Provincial Hospital in Poznan between June 2014 and June 2016. The analysis includes age, sex, the localization of lesions, histopathological and microbiological results, an extension of the surgery and treatment results. Results: Over the analyzed period of time, 415 FESS for chronic sinusitis were performed. In this group, 83 patients underwent surgery for USD. There were 35 women and 48 men.CRS was found in 48 cases, mycosis in nine cases, 12 patients were operated for non-malignant tumors, such as inverted papilloma (9), osteoma (2) and fibrosis tumor(1); seven patients had a choanal polyp and two of them had a foreign body in maxillary sinus – a tooth root lying loose. Four patients were diagnosed with a hypoplastic maxillary sinus and one patient suffered from frontal sinus pyocele. One side endoscopic opening of all sinuses was performed in the group with CRS, endoscopic medial maxillectomy was conducted in patients with inverted papilloma, and an isolated opening of the affected sinus was performed in the cases with mycosis. Conclusions: USD must be always suspected of malignant degeneration until proven otherwise. Endoscopic sinus surgery with the use of angled scope allows for the removal of even very extensive lesions. In our opinion, the extent of operation is determined by the nature of pathology. While extensive surgery is recommended in patients with inverted papilloma, a limited procedure should be performed in those with isolated mycosis

Prognostic factors in oral and oropharyngeal cancer based on ultrastructural analysis and DNA methylation of the tumor and surgical margin

Oral and oropharyngeal cancers are characterized by relatively low 5- year survival rates due to many factors, including local recurrence. The identification of new molecular markers may serve for the estimation of prognosis and thus augment treatment decisions and affect therapy outcome. The aim of this study was to describe the morphological characteristics and the DNA methylation status of the CDKN2A,CDH1, ATM, FHIT and RAR- genes in the central and peripheral part of the tumor and the surgical margin and evaluate their prognostic significance. 53 patients with oral and oropharyngeal cancer were enrolled to the prospective study, and had been primarily treated surgically. Correlations between morphological data, hypermethylation status and clinicopathological data, as well as prognosis, were assessed. Nuclei polymorphism highly correlated with T stage (p < 0.0001), N stage (p < 0.046), and metastases to the lymph nodes pN (p < 0.004 ). Also, the number of cells in irregular mitosis correlated with T stage (p < 0.004), and highly with pN (p < 0.009). The significance of CDKN2A hypermethylation as a good prognostic factor was also established in the Kaplan-Meir test. The ultrastructural analysis showed that none of the examined tumors had homogenous texture and that resection margin specimens clean in HE stained tissue samples frequently contained single tumor cells or few cells in groups surrounded by connective tissue. This indicates the superiority of electron microscopy over standard histopathological analysis. Thus, a combination of such morphological examination with epigenetic parameters described herein could result in the discovery of promising new prognostic markers of the disease