Strategy.

While the establishment of an ovarian cancer biobank from patient-derived organoids along with their clinical background information promises advances in research and patient care, standardization remains a challenge due to the heterogeneity of this lethal malignancy, combined with the inherent complexity of organoid technology. This adaptable protocol provides a systematic framework to realize the full potential of ovarian cancer organoids considering a patient-specific variability of progenitors. By implementing a structured experimental workflow to select optimal culture conditions and seeding methods, with parallel testing of direct 3D seeding versus a 2D/3D route, we obtain, in most cases, robust long-term expanding lines suitable for a broad range of downstream applications. Notably, the protocol has been tested and proven efficient in a great number of cases (N = 120) of highly heterogeneous starting material, including high-grade and low-grade ovarian cancer and stages of the disease with primary debulking, recurrent disease, and post-neoadjuvant surgical specimens. Within a low Wnt, high BMP exogenous signaling environment, we observed progenitors being differently susceptible to the activation of the Heregulin 1 ß (HERß-1)-pathway, with HERß-1 promoting organoid formation in some while inhibiting it in others. For a subset of the patient's samples, optimal organoid formation and long-term growth necessitate the addition of fibroblast growth factor 10 and R-Spondin 1 to the medium. Further, we highlight the critical steps of tissue digestion and progenitor isolation and point to examples where brief cultivation in 2D on plastic is beneficial for subsequent organoid formation in the Basement Membrane Extract type 2 matrix. Overall, optimal biobanking requires systematic testing of all main conditions in parallel to identify an adequate growth environment for individual lines. The protocol also describes the handling procedure for efficient embedding, sectioning, and staining to obtain high-resolution images of organoids, which is required for comprehensive phenotyping.

Genetics and beyond: Precision Medicine Real-World Data for Patients with Cervical, Vaginal or Vulvar Cancer in a Tertiary Cancer Center.

Advances in molecular tumor diagnostics have transformed cancer care. However, it remains unclear whether precision oncology has the same impact and transformative nature across all malignancies. We conducted a retrospective analysis of patients with human papillomavirus (HPV)-related gynecologic malignancies who underwent comprehensive molecular profiling and subsequent discussion at the interdisciplinary Molecular Tumor Board (MTB) of the University Hospital, LMU Munich, between 11/2017 and 06/2022. We identified a total cohort of 31 patients diagnosed with cervical (CC), vaginal or vulvar cancer. Twenty-two patients (fraction: 0.71) harbored at least one mutation. Fifteen patients (0.48) had an actionable mutation and fourteen (0.45) received a recommendation for a targeted treatment within the MTB. One CC patient received a biomarker-guided treatment recommended by the MTB and achieved stable disease on the mTOR inhibitor temsirolimus for eight months. Factors leading to non-adherence to MTB recommendations in other patient cases included informed patient refusal, rapid deterioration, stable disease, or use of alternative targeted but biomarker-agnostic treatments such as antibody-drug conjugates or checkpoint inhibitors. Despite a remarkable rate of actionable mutations in HPV-related gynecologic malignancies at our institution, immediate implementation of biomarker-guided targeted treatment recommendations remained low, and access to targeted treatment options after MTB discussion remained a major challenge.

Do Disinfectant Solutions during Gargling Reach the Pharynx?

INTRODUCTION: In times of COVID-19, gargling disinfectant is commonly used. Disinfectant solutions seem to decrease the infection's symptoms. For disinfection, several techniques are reported. So far, there are no data about the regions in the upper airways achieved by gargled fluid. METHODS: Ten healthy volunteers without any dysphagia were investigated with a high-sensitivity flexible endoscopic evaluation of swallowing (hsFEES®) during and after gargling colored water. One volunteer repeated the gargling process in fast and real-time MRI. RESULTS: In all cases, no color accumulation was detected on the posterior pharyngeal wall, epi- or hypopharynx during gargling. The MRI scans confirmed the results. CONCLUSIONS: hsFEES® and fast MRI provide an insight into the gargling pattern. Data show that during gargling, the fluid covers the soft tissue in the oral cavity and the anterior part of the soft palate, but not the posterior pharyngeal wall nor the epi- and hypopharynx.

Comparison of three different image enhancement systems for detection of laryngeal lesions.

OBJECTIVE: Image enhancement systems are important diagnostic tools in the detection of laryngeal pathologies. This study aimed to compare three different image enhancement systems: professional image enhancement technology, Image1 S and narrow-band imaging. METHOD: Using the three systems, 100 patients with laryngeal lesions were investigated using a flexible and a 30° rigid endoscope. The lesions were diagnosed by three experts and classified using the Ni classification. The findings were compared. RESULTS: Lesions classified as 'benign' were histopathologically confirmed in 50 per cent of patients, malignant lesions were confirmed in 41 per cent and recurrent respiratory papillomatosis were confirmed in 9 per cent. There was no significant difference between the experts' assessments of each image enhancement system. CONCLUSION: The three systems give comparable results in the detection of laryngeal lesions. With two additional systems, more users can perform image-enhanced endoscopy, resulting in a broadly available tool that can help to improve oncological assessment.

Protocol to optimize the biobanking of ovarian cancer organoids by accommodating patient-specific differences in stemness potential.

We present a protocol for effective biobanking of epithelial ovarian cancer organoids, considering the heterogeneous clinical presentation and high recurrence rates. Our protocol involves parallel testing of three media to identify patient-specific optimal conditions. We describe steps for tissue dissociation, differential seeding, organoid cultivation, and biobanking. We outline procedures for fixation, embedding, and staining for confocal imaging. Furthermore, we demonstrate that brief cultivation of isolates in 2D on plastic enhances organoid-forming potential in selected lines, expanding their application scope. For complete details on the use and execution of this protocol, please refer to Hoffmann et al.1.

Nuclear receptor co-repressor NCOR2 and its relation to GPER with prognostic impact in ovarian cancer.

PURPOSE: The significance of the non-classical G-protein-coupled estrogen receptor (GPER) as positive or negative prognostic factor for ovarian cancer patients remains still controversial. Recent results indicate that an imbalance of both co-factors and co-repressors of nuclear receptors regulates ovarian carcinogenesis by altering the transcriptional activity through chromatin remodeling. The present study aims to investigate whether the expression of the nuclear co-repressor NCOR2 plays a role in GPER signaling which thereby could positively impact overall survival rates of ovarian cancer patients. METHODS: NCOR2 expression was evaluated by immunohistochemistry in a cohort of 156 epithelial ovarian cancer (EOC) tumor samples and correlated with GPER expression. The correlation and differences in clinical and histopathological variables as well as their effect on prognosis were analyzed by Spearman's correlation, Kruskal-Wallis test and Kaplan-Meier estimates. RESULTS: Histologic subtypes were associated with different NCOR2 expression patterns. More specifically, serous and mucinous EOC demonstrated a higher NCOR2 expression (P = 0.008). In addition, high nuclear NCOR2 expression correlated significantly with high GPER expression (cc = 0.245, P = 0.008). A combined evaluation of both high NCOR2 (IRS > 6) and high GPER (IRS > 8) expression revealed an association of a significantly improved overall survival (median OS 50.9 versus 105.1 months, P = 0.048). CONCLUSION: Our results support the hypothesis that nuclear co-repressors such as NCOR2 may influence the transcription of target genes in EOC such as GPER. Understanding the role of nuclear co-repressors on signaling pathways will allow a better understanding of the factors involved in prognosis and clinical outcome of EOC patients.

PLA2G7/PAF-AH as Potential Negative Regulator of the Wnt Signaling Pathway Mediates Protective Effects in BRCA1 Mutant Breast Cancer.

Past studies have confirmed that aberrant activation of the Wnt/ß-catenin signaling is associated with tumorigenesis and metastasis in breast cancer, while the role of platelet-activating factor acetylhydrolase (PLA2G7/PAF-AH) in this signaling pathway remains unclear. In this study, we analyze the functional impact of PAF-AH on BRCA1 mutant breast cancer and explore its relationship to the Wnt signaling pathway. By performing immunohistochemistry, PAF-AH expression and ß-catenin expression were examined in both BRCA1 WT and BRCA1 mutant breast cancer specimens. The BRCA1 mutant breast cancer cell line HCC1937 was used for in vitro experiments to assess the impact of PAF-AH on cellular functions. The intracellular distribution of ß-catenin depending on PLA2G7/PAF-AH expression was investigated by immunocytochemistry. Significantly higher nuclear expression levels of PAF-AH were found in BRCA1 mutant tissue specimens than in BRCA1 WT samples. Cell viability, proliferation, and the motility rate of HCC1937 were significantly enhanced after PLA2G7 silencing, which indicated a protective role of PAF-AH in breast cancer. Nuclear PAF-AH expressed correlatedly with membranous ß-catenin. PLA2G7 silencing provoked the ß-catenin translocation from the membrane to the nucleus and activated Wnt signaling downstream genes. Our data showed a protective effect of high PAF-AH expression in BRCA1 mutant breast cancer. PAF-AH may achieve its protective effect by negatively regulating the Wnt pathway. In conclusion, our research sheds new light on the regulatory pathways in BRCA1 mutant breast cancer.

Expression pattern and prognostic potential of histamine receptors in epithelial ovarian cancer.

PURPOSE: Despite recent advances in the treatment of ovarian cancer (OC), long-term remissions remain scarce. For a targeted approach, prognostic markers are indispensable for predicting survival and treatment response. Given their association with multiple hallmarks of cancer, histamine receptors (HR) are emerging as promising candidates. Here, we investigate their expression pattern and prognostic value in OC. METHODS: Specimens of 156 epithelial OC patients were collected during cytoreductive surgery at the Department of Obstetrics and Gynecology, LMU, between 1990 and 2002 and combined in a tissue microarray. Immunohistochemical staining of the HR H1, H2, H3 and H4 was quantified by an immunoreactive score and linked with clinico-pathological data by Spearman's correlation. Via ROC curve analysis, optimal cut-off values for potential prognostic markers were defined. Overall survival (OS) was visualized in Kaplan-Maier curves and significances determined by log-rank testing. A Cox regression model was applied for multivariate analysis. RESULTS: HR H3 and H4 expression was restricted to the cytosol of OC cells, while H1 was also present in the nucleus. A significant association between HR H1, H3 and H4 expression with several clinico-pathological parameters was revealed. In addition, HR H1 and H3 expression correlated positively, HR H4 expression negatively with OS. In addition, HR H3 was identified as independent prognostic marker for OS. HR H2 expression had no prognostic value. CONCLUSIONS: HR H1, H3 and H4 could serve as potential predictors for OS of OC patients. Further research is warranted to elucidate their pathophysiologic role and their predictive and therapeutic potential in OC.

High RIG-I and EFTUD2 expression predicts poor survival in endometrial cancer.

PURPOSE: Endometrial cancer is the most common gynecological malignancy. The helicase RIG-I, a part of the innate immune system, and EFTUD2, a splicing factor which can upregulate RIG-I expression, are shown to influence tumor growth and disease progression in several malignancies. For endometrial cancer, an immunogenic cancer, data about RIG-I and EFTUD2 are still missing. The aim of this study was to examine the expression of RIG-I and EFTUD2 in endometrial cancer. METHODS: 225 specimen of endometrial cancer were immunohistochemically stained for RIG-I and EFTUD2. The results were correlated to clinicopathological data, overall survival (OS) and progression-free survival (PFS). RESULTS: High RIG-I expression correlated with advanced tumor stages (FIGO: p = 0.027; pT: p = 0.010) and worse survival rates (OS: p = 0.009; PFS: p = 0.022). High EFTUD2 expression correlated to worse survival rates (OS: p = 0.026; PFS: p < 0.001) and was determined to be an independent marker for progression-free survival. CONCLUSION: Our data suggest that the expression of RIG-I and EFTUD2 correlates with survival data, which makes both a possible therapeutic target in the future.

Fixed-Bearing Trabecular Metal Total Ankle Arthroplasty Using the Transfibular Approach for End-Stage Ankle Osteoarthritis: An International Non-Designer Multicenter Prospective Cohort Study.

This multicenter prospective cohort study assessed the safety and performance of the Trabecular Metal Total Ankle System (TM Ankle; Zimmer) for primary total ankle arthroplasty (TAA). Methods: One hundred and twenty-one consecutive patients qualifying for primary TAA were enrolled in the study. All patients received the TM Ankle implant. Clinical outcome examinations and radiographic evaluations were conducted at 6 weeks, 6 months, 1 year, 2 years, and 3 years. Patient-reported outcome measures (PROMs) were evaluated with use of the EuroQol-5 Dimensions questionnaire (EQ-5D), Ankle Osteoarthritis Scale (AOS), American Orthopaedic Foot & Ankle Society questionnaire (AOFAS), and patient satisfaction at each time point. Complications were classified according to the Canadian Orthopaedic Foot and Ankle Society (COFAS) system. Results: The average AOFAS, EQ-5D, AOS pain, and AOS difficulty scores showed significant improvement at 6 weeks, 6 months, 1 year, 2 years, and 3 years as compared with the preoperative baseline (p < 0.001). The Kaplan-Meier survival estimate for revision when used in primary cases was 97.35% at 3 years. During the 3 years of follow-up, 9 patients showed abnormal radiographic findings. Two ankles had intraoperative complications, 38 had complications that were non-surgical or device-related, and 3 ankles underwent revision. Conclusions: The results of the present study indicated that patient well-being significantly increased following TAA with use of the TM Ankle. Radiographic parameters also demonstrated a low incidence of abnormal findings. Level of Evidence: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

AKR1C1/2 inhibition by MPA sensitizes platinum resistant ovarian cancer towards carboplatin.

In recurrent epithelial ovarian cancer (EOC) most patients develop platinum-resistance. On molecular level the NRF2 pathway, a cellular defense mechanism against reactive oxygen species, is induced. In this study, we investigate AKR1C1/2, target of NRF2, in a well-established EOC collective by immunohistochemistry and in a panel of ovarian cancer cell lines including platinum-resistant clones. The therapeutic effect of carboplatin and MPA as monotherapy or in combination was assessed by functional assays, using OV90 and OV90cp cells. Molecular mechanisms of action of MPA were investigated by NRF2 silencing and AKR activity measurements. Immunohistochemical analysis revealed that AKR1C1/2 is a key player in the development of chemoresistance and an independent indicator for short PFS (23.5 vs. 49.6 months, p = 0.013). Inhibition of AKR1C1/2 by MPA led to a concentration- and time-dependent decline of OV90 viability and to an increased response to CP in vitro. By NRF2 silencing, however, the effects of MPA treatment were reduced. Concludingly, our data suggest that a combination therapy of carboplatin and MPA might be a promising therapeutic approach to increase response rates of EOC patients, which should be explored in clinical context.

High-sensitivity FEES® with the professional image enhancement technology "PIET".

PURPOSE: Flexible endoscopic evaluation of swallowing (FEES®) is a standard diagnostic tool in dysphagia. The combination of FEES® and narrow band light (narrow band imaging; NBI) provides a more precise and detailed investigation method. So far, this technique could only be performed with the NBI illumination. The new version of the "professional image enhancement technique" (PIET) provides another image enhancing system. This study investigates the eligibility of PIET in the FEES® procedure. METHODS: Both techniques, NBI and PIET, were compared using a target system. Furthermore, the image enhancement during FEES® was performed and recorded with the two systems during daily routine. RESULTS: Performing an image enhancement during FEES® is possible with both systems PIET and NBI. On the target system, the contrast of the PIET showed a brighter and a more detailed picture. In dysphagia patients, no difference between PIET and NBI was detected. CONCLUSIONS: PIET proved to be non-inferior to NBI during image enhancement FEES®. So far, image enhancement FEES® was exclusively connected to NBI. With the PIET system, an alternative endoscopy technology is available for certain indications.

Actin Beta-Like 2 as a New Mediator of Proliferation and Migration in Epithelial Ovarian Cancer.

The impact of Actin beta-like 2 (ACTBL2), a novel described actin isoform, on epithelial ovarian cancer (EOC) biology has not been investigated so far. In this study, we analyzed the prognostic and functional significance of ACTBL2 and its regulatory element Nuclear factor of activated T-cells 5 (NFAT5). The expression of ACTBL2 and NFAT5 was examined in tissue microarrays of 156 ovarian cancer patients by immunohistochemistry. Aiming to assess the molecular impact of ACTBL2 on cellular characteristics, functional assays were executed in vitro upon siRNA knockdown of ACTBL2 and NFAT5. ACTBL2 expression was identified as an independent negative prognostic factor for overall survival of EOC patients. EOC cell lines showed a significantly increased mRNA and protein level of ACTBL2 compared to the benign control. In vitro analyses upon siRNA knockdown of ACTBL2 displayed a significantly reduced cellular viability, proliferation and migration. siRNA knockdown of NFAT5 proved a significant molecular interplay by inducing a downregulation of ACTBL2 with a thus resulting concordant alteration in cellular functions, predominantly reflected in a decreased migratory potential of EOC cells. Our results provide significant evidence on the negative prognostic impact of ACTBL2 in EOC, suggesting its crucial importance in ovarian carcinogenesis by modulating cellular motility and proliferation.

The Platelet-Activating Factor Receptor's Association with the Outcome of Ovarian Cancer Patients and Its Experimental Inhibition by Rupatadine.

The platelet-activating factor receptor (PAFR) and its ligand (PAF) are important inflammatory mediators that are overexpressed in ovarian cancer. The receptor is an important player in ovarian cancer development. In this study, we aimed to evaluate the prognostic value of PAFR in epithelial ovarian cancer (EOC) and the potential use of its antagonist, rupatadine, as an experimental treatment. Tissue microarrays of ovarian cancer patients, most markedly those with a non-mucinous subtype, immunohistochemically overexpressed PAFR. Elevated cytoplasmic PAFR expression was found to significantly and independently impair patients' overall and recurrence-free survival (OS: median 83.48 vs. 155.03 months; p = 0.022; RFS: median 164.46 vs. 78.03 months; p = 0.015). In vitro, the serous ovarian cancer subtypes especially displayed an elevated PAFR gene and protein expression. siRNA knockdown of PAFR decreased cell proliferation significantly, thus confirming the receptor's protumorigenic effect on ovarian cancer cells. The clinically approved PAFR antagonist rupatadine effectively inhibited in vitro cell proliferation and migration of ovarian cancer cells. PAFR is a prognostic marker in ovarian cancer patients and its inhibition through rupatadine may have important therapeutic implications in the therapy of ovarian cancer patients.

Rare Diseases of Larynx, Trachea and Thyroid. / Seltene Erkrankungen des Larynx, der Trachea und der Schilddrüse.

This review article covers data on rare diseases of the larynx, the trachea and the thyroid. In particular, congenital malformations, rare manifestations of inflammatory laryngeal disorders, benign and malignant epithelial as well as non-epithelial tumors, laryngeal and tracheal manifestations of general diseases and, finally, thyroid disorders are discussed. The individual chapters contain an overview of the data situation in the literature, the clinical appearance of each disorder, important key points for diagnosis and therapy and a statement on the prognosis of the disease. Finally, the authors indicate on study registers and self-help groups.

Understanding the psychological impact of the COVID-19 pandemic and containment measures: An empirical model of stress.

Epidemics such as COVID-19 and corresponding containment measures are assumed to cause psychological stress. In a survey during the lockdown in Switzerland (n = 1565), we found substantially increased levels of stress in the population. In particular, individuals who did not agree with the containment measures, as well as those who saw nothing positive in the crisis, experienced high levels of stress. In contrast, individuals who are part of a risk group or who are working in healthcare or in essential shops experienced similar stress levels as the general public. The psychological mechanisms that determine stress, caused by the COVID-19 pandemic and containment measures, are not yet clear. Thus, we conducted a path analysis to gain a deeper understanding of the psychological mechanisms that lead to stress. Experiencing fear of the disease is a key driver for being worried. Our model further shows that worries about the individual, social, and economic consequences of the crisis, strongly boost stress. The infection rate in the canton (i.e., state) of residence also contributes to stress. Positive thinking and perceived social, organizational, and governmental support mitigate worries and stress. Our findings indicate that containment measures increase worries and stress, especially for those who feel that these measures either are not sufficient or go too far. Thus, highlighting positive aspects of the crisis and convincing people of the effectiveness and necessity of mitigation measures can, not only promote compliance, but also reduce stress. Our model suggests that people who feel protected by the authorities have fewer worries, which can, in turn, limit the negative impact of the crisis on mental health.

Use of Transversus Abdominis Plane (TAP) Blocks for Postoperative Pain Management in a Patient With an Open Abdomen: A Case Report and Review of Literature.

In light of the superior analgesia and opioid sparing effects provided by transversus abdominis plane (TAP) blocks, numerous new techniques and applications have evolved. However, TAP blocks are still underutilized in the critical care setting, and PubMed­listed reports on the relevance of TAP integrity for TAP block efficacy are lacking. Here, we report bilateral TAP blocks delivering quick, potent and durable pain relief to a patient with open abdomen (OA) after prior management with opioids and epidural anesthesia had failed. Extending TAP block application to OA patients even in the post­operative setting might hence reduce opioid consumption and quicken reconvalescence.

PD1-CD28 Fusion Protein Enables CD4+ T Cell Help for Adoptive T Cell Therapy in Models of Pancreatic Cancer and Non-hodgkin Lymphoma.

Background: Interaction of the programmed death receptor 1 (PD-1) and its ligand, PD-L1, suppresses T cell activity and permits tumors to evade T cell-mediated immune surveillance. We have recently demonstrated that antigen-specific CD8+ T cells transduced with a PD1-CD28 fusion protein are protected from PD-1-mediated inhibition. We have now investigated the potential of PD1-CD28 fusion protein-transduced CD4+ T cells alone or in combination with CD8+ T cells for immunotherapy of pancreatic cancer and non-Hodgkin lymphoma. Methods: OVA-specific CD4+ and CD8+ were retrovirally transduced with the PD1-CD28 fusion protein. Cytokine release, proliferation, cytotoxic activity, and phenotype of transduced T cells were assessed in the context of Panc02-OVA (murine pancreatic cancer model) and E.G7-PD-L1 (murine T cell lymphoma model) cells. Results: Stimulation of PD1-CD28 fusion protein-transduced CD4+ T cells with anti-CD3 and recombinant PD-L1 induced specific T cell activation, as measured by IFN-y release and T cell proliferation. Coculture with Panc02-OVA or E.G7-PD-L1 tumor cells also led to specific activation of CD4+ T cells. Cytokine release and T cell proliferation was most effective when tumor cells simultaneously encountered genetically engineered CD4+ and CD8+ T cells. Synergy between both cell populations was also observed for specific tumor cell lysis. T cell cytotoxicity was mediated via granzyme B release and mediated enhanced tumor control in vivo. Transduced CD4+ and CD8+ T cells in co-culture with tumor cells developed a predominant central memory phenotype over time. Different ratios of CD4+ and CD8+ transduced T cells led to a significant increase of IFN-y and IL-2 secretion positively correlating with CD4+ T cell numbers used. Mechanistically, IL-2 and MHC-I were central to the synergistic activity of CD4+ and CD8+ T cells, since neutralization of IL-2 prevented the crosstalk between these cell populations. Conclusion: PD1-CD28 fusion protein-transduced CD4+ T cells significantly improved anti-tumoral effect of fusion protein-transduced CD8+ T cells. Thus, our results indicate that PD1-CD28 fusion protein-transduced CD4+ T cells have the potential to overcome the PD-1-PD-L1 immunosuppressive axis in pancreatic cancer and non-Hodgkin lymphoma.

[Microvascular reconstruction of the larynx following total laryngectomy]. / Mikrovaskuläre Kehlkopfrekonstruktion nach totaler Laryngektomie.

Total laryngectomy still is a standard procedure for the treatment of advanced laryngeal or hypopharyngeal carcinoma. The unavoidable loss of voice may lead to serious impairments in quality of life. The most common technique of voice restoration is the tracheal-esophageal puncture combined with the application of a voice prosthesis. Laryngeal reconstruction with a radial forearm flap represents a possible surgical method of voice restoration. This study is a mono-center retrospective analysis of patients receiving a so-called laryngoplasty after total laryngectomy between 2006 and 2015, focusing on long-term functional outcome and complications. 39 patients were included. Sufficient phonation was possible in 77 %, finger-free speaking was achieved in 62 %. Exclusion of irradiated patients revealed a rehabilitation rate of 91 %. The most common early complication was cervical hematoma in 15 %, whereas no loss of flap was assessed. Stenosis of the laryngoplasty was seen in 7 cases, mainly post-irradiation. The rate of successful voice restoration is equal in both, laryngoplasty and voice prosthesis patients. However, voice quality is better after surgical reconstruction. Complications induced by the voice prosthesis, which may be severe in some cases, were not seen in the study group. Furthermore, life-long support by an ENT specialist regarding voice prosthesis exchange is not necessary. Assuming correct choice of candidates, laryngoplasty is a sufficient method for voice restoration after laryngectomy.