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1.
Front Oncol ; 12: 795277, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35296001

RESUMO

Background: Pembrolizumab and cetuximab are antibodies under investigation in head and neck squamous cell carcinoma (HNSCC) either as single agents or combined with cisplatin and other chemotherapeutic drugs, e.g., 5-fluorouracil and/or docetaxel. However, also the combination of both antibodies may have potential in recurrent/metastatic (R/M) HNSCC, in particular in cisplatin-resistant or -refractory cases or patients with comorbid disease, e.g. patients with impaired renal function. Methods: To clarify potential benefit that may result from such combination, we used the FLAVINO assay, a short-time ex vivo assay to compare responsiveness of HNSCC to pembrolizumab, cetuximab and both combined regarding colony formation of epithelial cells of biopsy-derived tumor samples and their cytokine production within three days either without or with stimulation with 10 ng/mL interferon gamma (IFN-γ). Vascular endothelial growth factor A (VEGF), monocyte chemoattractant protein 1 (MCP-1 or CCL2), interleukin 6 (IL-6), IL-8, IFN-γ, and interferon gamma-induced protein 10 (IP-10 or CXCL10) in supernatants were measured by ELISA. Results: We detected huge heterogeneity in response to cetuximab, pembrolizumab and both combined with and without IFN-γ stimulation. Moreover, we detected a link between IFN-γ induced IP-10 release and improved outcome in those HNSCC patients who were capable to respond to IFN-γ and pembrolizumab, cetuximab and both combined with a further increase in IP-10 production. We derived an "IP-10 score" that independent from clinical characteristics of HNSCC patients and therapy regimens applied was able to predict their outcome. Conclusions: The heterogeneity in the ex vivo response of cetuximab, pembrolizumab and both combined with and without IFN-γ stimulation identifies subgroups of HNSCC patients with deviating OS.

3.
Front Oncol ; 11: 737080, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34868927

RESUMO

BACKGROUND: Standardized staging procedures and presentation of oral squamous cell carcinoma (OSCC) patients in multidisciplinary tumor boards (MDTB) before treatment and utilization of elective neck dissection (ND) are expected to improve the outcome, especially in local advanced LAOSCC (UICC stages III-IVB). As standardized diagnostics but also increased heterogeneity in treatment applied so far have not been demonstrated to improve outcome in LAOSCC, a retrospective study was initiated. METHODS: As MDTB was introduced into clinical routine in 2007, 316 LAOSCC patients treated during 1991-2017 in our hospital were stratified into cohort 1 treated before (n=104) and cohort 2 since 2007 (n=212). Clinical characteristics, diagnostic procedures and treatment modality of patients were compared using Chi-square tests and outcome analyzed applying Kaplan-Meier plots and log-rank tests as well as Cox proportional hazard regression. Propensity scores (PS) were used to elucidate predictors for impaired distant metastasis-free survival (DMFS) in PS-matched patients. RESULTS: Most patient characteristics and treatment modalities applied showed insignificant alteration. Surgical treatment included significantly more often resection of the primary tumor plus neck dissection, tracheostomy and percutaneous endoscopic gastrostomy tube use. Cisplatin-based chemo-radiotherapy was the most frequent. Only insignificant improved disease- (DFS), progression- (PFS) and event-free (EFS) as well as tumor-specific (TSS) and overall survival (OS) were found after 2006 as local (LC) and loco-regional control (LRC) were significantly improved but DMFS significantly impaired. Cox regression applied to PS-matched patients elucidated N3, belonging to cohort 2 and cisplatin-based chemo-radiotherapy as independent predictors for shortened DMFS. The along chemo-radiotherapy increased dexamethasone use in cohort 2 correlates with increased DM. CONCLUSIONS: Despite standardized diagnostic procedures, decision-making considering clear indications and improved therapy algorithms leading to improved LC and LRC, shortened DMFS hypothetically linked to increased dexamethasone use had a detrimental effect on TSS and OS.

4.
Infect Drug Resist ; 14: 2309-2319, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34188497

RESUMO

PURPOSE: Postoperative mediastinitis after cardiac surgery is still a devastating complication. Insufficient microbiological specimens obtained by superficial swabbing may only detect bacteria on the surface, but pathogens that are localized in the deep tissue may be missed. The aim of this study was to analyze deep sternal wound infection (DSWI) samples by conventional microbiological procedures and fluorescence in situ hybridization (FISH) in order to discuss a diagnostic benefit of the culture-independent methods and to map spatial organization of pathogens and microbial biofilms in the wounds. METHODS: Samples from 12 patients were collected and analyzed using classic microbiological culture and FISH in combination with molecular nucleic acid amplification techniques (FISHseq). Frequency of and the time to occurrence of a DSWI was recorded, previous operative interventions, complications, as well as individual risk factors and the microbiologic results were documented. RESULTS: Tissue samples were taken from 12 patients suffering from DSWI. Classical microbiological culture resulted in the growth of microorganisms in the specimens of five patients (42%), including bacteria and in one case Candida. FISHseq gave additional diagnostic information in five cases (41%) and confirmed culture results in seven cases (59%). CONCLUSION: Microbial biofilms are not always present in DSWI wounds, but microorganisms are distributed in a "patchy" pattern in the tissue. Therefore, a deep excision of the wound has to be performed to control the infection. We recommend to analyze at least two wound samples from different locations by culture and in difficult to interpret cases, additional molecular biological analysis by FISHseq.

5.
Front Oncol ; 11: 682088, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34026656

RESUMO

BACKGROUND: About five to 10% of cancers in the head and neck region are neck squamous cell carcinoma of unknown primary (NSCCUP). Their diagnosis and treatment are challenging given the risk of missing occult tumors and potential relapse. Recently, we described human papillomavirus (HPV)-related NSCCUP-patients (NSCCUP-P) as a subgroup with superior survival. However, standardized diagnostic workup, novel diagnostic procedures, decision-making in the multidisciplinary tumor board (MDTB) and multimodal therapy including surgery and post-operative radio-chemotherapy (PORCT) may also improve survival. METHODS: For assessing the impact of standardized diagnostic processes simultaneously established with the MDTB on outcome, we split our sample of 115 NSCCUP-P into two cohorts treated with curative intent from 1988 to 2006 (cohort 1; n = 53) and 2007 to 2018 (cohort 2; n = 62). We compared diagnostic processes and utilized treatment modalities applying Chi-square tests, and outcome by Kaplan-Meier plots and Cox regression. RESULTS: In cohort 2, the standardized processes (regular use of [18F]-FDG-PET-CT imaging followed by examination under anesthesia, EUA, bilateral tonsillectomy and neck dissection, ND, at least of the affected site) improved detection of primaries (P = 0.026) mostly located in the oropharynx (P = 0.001). From 66.0 to 87.1% increased ND frequency (P = 0.007) increased the detection of extracapsular extension of neck nodes (ECE+) forcing risk factor-adapted treatment by increased utilization of cisplatin-based PORCT that improved 5-years progression-free and overall survival from 60.4 and 45.3 to 67.7% (P = 0.411) and 66.1% (P = 0.025). CONCLUSIONS: Standardized diagnostic workup followed by ND and risk-factor adapted therapy improves survival of NSCCUP-P.

7.
Cancer ; 126(9): 1856-1872, 2020 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-32032442

RESUMO

BACKGROUND: Human papillomavirus (HPV)-driven oropharyngeal squamous cell carcinomas (OPSCCs) demonstrate superior outcome compared with HPV-negative OPSCCs. The eighth edition of the American Joint Committee on Cancer/Union for International Cancer Control (AJCC/UICC) tumor, lymph node, metastasis (TNM) classification (TNM 2017) modifies OPSCC staging based on p16 positivity as a surrogate for HPV-driven disease. In p16-negative OPSCCs, lymph node (N) categories include extracapsular/extranodal extension (ECE); and, in p16-positive OPSCCs, N categories are based on the number of positive neck lymph nodes omitting ECE status. The objective of the current study was to assess the prognostic impact of positive ECE status and the detection of HPV16 DNA in patients with p16-positive OPSCC. METHODS: In a cohort of 92 patients with p16-positive, lymph node (N)-positive (stage III-IVB) OPSCC who underwent surgery and neck dissection, allowing for a pathologic examination of positive lymph nodes, 66 of 92 patients (71.4%) were p16-positive/HPV16 DNA-positive, 62 of 92 (67%) were ECE-positive, and 45 of 62 (72.6%) were ECE-positive, p16-positive, and HPV16 DNA-positive. Differences in outcome were assessed using Kaplan-Meier plots and Cox proportional hazard regression (CoxR) for tumor-specific survival and overall survival (OS). RESULTS: The mean numbers of positive lymph nodes in ECE-positive patients (5.0 positive lymph nodes; 95% CI, 3.8-6.4 positive lymph nodes) and ECE-negative patients (2.4 positive lymph nodes; 95% CI, 1.8-2.9 positive lymph nodes) were different (P = .0007). ECE affected OS and tumor-specific survival in p16-positive patients (P = .007 and P = .047, respectively) and in p16-positive/HPV16 DNA-positive patients (P = .013 and P = .026, respectively). Related to the unequal distributions of ECE-positive/HPV16 DNA-negative tumors, the TNM 2017 failed to discriminate OS in patients with UICC stage I, II, and III disease (mean OS, 54.5, 73.4, and 45 months, respectively; median OS, 64.7 months, not reached, and 41.1 months, respectively). According to a univariate CoxR, the presence of ECE predicted impaired OS in patients with p16-positive OPSCC (hazard ratio, 3.40; 95% CI, 1.17-9.89; P = .025) and even greater impaired OS in those with p16-positive/HPV16 DNA-positive OPSCC (HR, 8.64; 95% CI, 1.12-66.40; P = .038). Multivariate CoxR confirmed ECE and HPV16 DNA detection as independent predictors. CONCLUSIONS: ECE and HPV16 DNA status should be included in the prognostic staging of patients with p16-positive OPSCC because several lines of evidence demonstrate their impact on survival.


Assuntos
Inibidor p16 de Quinase Dependente de Ciclina/metabolismo , Extensão Extranodal/patologia , Papillomavirus Humano 16/genética , Neoplasias Orofaríngeas/virologia , Infecções por Papillomavirus/metabolismo , Carcinoma de Células Escamosas de Cabeça e Pescoço/virologia , Adulto , Idoso , DNA Viral/genética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias Orofaríngeas/metabolismo , Neoplasias Orofaríngeas/patologia , Infecções por Papillomavirus/patologia , Prognóstico , Carcinoma de Células Escamosas de Cabeça e Pescoço/metabolismo , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Análise de Sobrevida
8.
Clin Case Rep ; 7(4): 686-688, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30997064

RESUMO

This case emphasizes the value of cardiac MRI and genetic testing in the early phase of ARVD/C. It also emphasizes the increased risk of SCD for patients with ARVD/C participating in competitive sports, even with immediate cardiopulmonary resuscitation.

9.
J Cardiothorac Surg ; 14(1): 31, 2019 02 05.
Artigo em Inglês | MEDLINE | ID: mdl-30722784

RESUMO

The original article [1] contains slight errors whereby several terms in the first column of Tables 1, 2, and 3 have an erroneous 'p' preceding them.

10.
J Cardiothorac Surg ; 14(1): 11, 2019 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-30651112

RESUMO

BACKGROUND: Estimation of lymph node status is essential in order to determine precise therapy for patients with non-small cell lung cancer (NSCLC). Furthermore, lymph node involvement is a very powerful prognostic factor in these patients. In this analysis, we aim to evaluate the predictive factors for lymph node metastasis in NSCLC-patients. METHODS: In a prospectively-established database, we analyzed all data of patients with NSCLC, who underwent oncological surgical resections from 01/2007 to 12/2016, retrospectively. The correlation between clinicopathological parameters and lymph node metastasis was investigated by using univariate and binary logistic regression analysis. RESULTS: In this study, we operated on 204 consecutive patients, 142 men (71.7%) and 56 women (28.3%). Lymph node metastases were detected in 38.2% (78/204). Preoperatively, central tumor localization (OR = 2.6, 95% CI = 1.3-5.1, P = 0.005) and tumor size > 3 cm (OR = 2.5, 95% CI = 1.3-4.4, P = 0.005) were found to be significant predictive factors for lymph node metastasis. Postoperatively, multivariate analysis showed that intratumoral lymph vessel invasion (L1-status) (OR = 17.3, 95% CI = 5.1-58.4, P <  0.001) along with the central tumor localization (OR = 2.8, 95% CI = 1.4-5.8, P = 0.004) were significantly associated with lymph node metastasis. In small size tumors (≤3 cm), two predictive factors for lymph node metastasis were found: central tumor localization (OR = 19.4, 95% = 2.1-186.4, P = 0.01) and L1-status (OR = 43.9, 95% CI = 3.6-529.4, P = 0.003). CONCLUSIONS: A precise pre- and intraoperative assessment of the lymph node status is essential in patients with larger sized tumors and central localization. Furthermore, L1-status is a highly significant risk factor for lymph node metastasis in NSCLC-Patients. Therefore, an adjuvant therapy in patients with L1-status and pNX category should be considered.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/cirurgia , Neoplasias Pulmonares/cirurgia , Linfonodos/patologia , Estadiamento de Neoplasias , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia , Broncoscopia , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Carcinoma Pulmonar de Células não Pequenas/secundário , Estudos de Casos e Controles , Feminino , Humanos , Neoplasias Pulmonares/patologia , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Prognóstico , Estudos Retrospectivos , Fatores de Risco
12.
Int J Cancer ; 142(7): 1361-1368, 2018 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-29159804

RESUMO

Treatment of patients with neck lymph node metastasis of squamous cell carcinoma (SCC) from unknown primary tumor (NSCCUP) is challenging due to the risk of missing occult tumors or inducing toxicity to unaffected sites. Human papillomavirus (HPV) is a promising biomarker given its causal link to oropharyngeal SCC and superior survival of patients with HPV-driven oropharyngeal SCC and NSCCUP. Identification of HPV-driven NSCCUP could focus diagnostic work-up and treatment on the oropharynx. For the first time, we assessed HPV antibodies and their prognostic value in NSCCUP patients. Antibodies against E6 and E7 (HPV16/18/31/33/35), E1 and E2 (HPV16/18) were assessed in 46 NSCCUP patients in sera collected at diagnosis, and in follow-up sera from five patients. In 28 patients, HPV tumor status was determined using molecular markers (HPV DNA, mRNA and cellular p16INK4a ). Thirteen (28%) NSCCUP patients were HPV-seropositive for HPV16, 18, 31, or 33. Of eleven patients with HPV-driven NSCCUP, ten were HPV-seropositive, while all 17 patients with non-HPV-driven NSCCUP were HPV-seronegative, resulting in 91% sensitivity (95% CI: 59-100%) and 100% specificity (95% CI: 80-100%). HPV antibody levels decreased after curative treatment. Recurrence was associated with increasing levels in an individual case. HPV-seropositive patients had a better overall and progression-free survival with hazard ratios of 0.09 (95% CI: 0.01-0.42) and 0.03 (95% CI: 0.002-0.18), respectively. For the first time, seropositivity to HPV proteins is described in NSCCUP patients, and high sensitivity and specificity for HPV-driven NSCCUP are demonstrated. HPV seropositivity appears to be a reliable diagnostic and prognostic biomarker for patients with HPV-driven NSCCUP.


Assuntos
Anticorpos Antivirais/análise , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/secundário , Neoplasias de Cabeça e Pescoço/diagnóstico , Neoplasias de Cabeça e Pescoço/secundário , Neoplasias Primárias Desconhecidas/patologia , Infecções por Papillomavirus/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/análise , Carcinoma de Células Escamosas/mortalidade , Intervalo Livre de Doença , Feminino , Neoplasias de Cabeça e Pescoço/mortalidade , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Neoplasias Primárias Desconhecidas/mortalidade , Neoplasias Primárias Desconhecidas/virologia , Papillomaviridae , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/mortalidade , Prognóstico , Sensibilidade e Especificidade , Carcinoma de Células Escamosas de Cabeça e Pescoço
13.
Eur Arch Otorhinolaryngol ; 274(7): 2927-2932, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28439693

RESUMO

Postoperative haemorrhage following tonsillectomy occurs in 5.98% of all cases with up to 10 deaths reported annually in Germany. When comparing tonsillectomy (TE) and tonsillotomy (TT), the same long-term frequency of ENT infections is displayed in children and young adults. However, taking postoperative haemorrhaging into account, TT is more favourable. Chronic tonsillitis is one of the most common indications for TE in the adult population; however, a histopathological characterization may reveal objective criteria and provide a foundation for routinely performing TT in adults too. Three essential parameters hyperplasia (HP), grade of inflammation (GOI) and activity of inflammation (AOI), which are responsible for, and associated with a clinically relevant disease were histopathologically examined in the tonsils of 100 adult patients with chronic recurrent tonsillitis. The parameters were analysed and compared separately in the pharyngeal and basal parts of the tonsils as well as in three sections (upper and lower pole of the tonsil, middle part) as this may influence the indication for TT. The comparison of the basal and pharyngeal portions displayed a significant difference in the GOI and the HP in all three sections: grade 2 HP as well as GOI were more commonly found in the basal than pharyngeal portions (p > 0.001). AOI (grade 2) displayed the same properties in the middle section (p < 0.002), but did not reach statistical significance in the cranial and caudal sections (p = 0.107 and p = 0.186). An overabundance of grade 1 GOI, AOI, and HP was seen in the pharyngeal sections. The results show that two out of three relevant parameters that demonstrate histopathological changes in recurrent inflamed tonsils have a significantly stronger presence in the basal section of the tonsil as opposed to the pharyngeal section. The processes initiated by inflammation next to the surface responsible for a clinically relevant recurrent tonsillitis seem to cause stronger reactions in the deep follicular portion of the tonsils.


Assuntos
Hemorragia Pós-Operatória , Tonsilectomia , Tonsilite , Adulto , Doença Crônica , Feminino , Alemanha , Humanos , Hiperplasia/patologia , Inflamação/diagnóstico , Inflamação/patologia , Masculino , Pessoa de Meia-Idade , Tonsila Palatina/imunologia , Tonsila Palatina/patologia , Hemorragia Pós-Operatória/diagnóstico , Hemorragia Pós-Operatória/etiologia , Hemorragia Pós-Operatória/imunologia , Tonsilectomia/efeitos adversos , Tonsilectomia/métodos , Tonsilite/diagnóstico , Tonsilite/imunologia , Tonsilite/fisiopatologia
14.
World J Transplant ; 5(4): 354-9, 2015 Dec 24.
Artigo em Inglês | MEDLINE | ID: mdl-26722664

RESUMO

In liver haemangiomas, the risk of complication rises with increasing size, and treatment can be obligatory. Here we present a case of a 46-year-old female who suffered from a giant haemangioma causing severe portal hypertension and vena cava compression, leading to therapy refractory ascites, hyponatremia and venostasis-associated thrombosis with pulmonary embolism. The patients did not experience tumour rupture or consumptive coagulopathy. Surgical resection was impossible because of steatosis of the non-affected liver. Orthotopic liver transplantation was identified as the only treatment option. The patient's renal function remained stable even though progressive morbidity and organ allocation were improbable according to the patient's lab model for end-stage liver disease (labMELD) score. Therefore, non-standard exception status was approved by the European organ allocation network "Eurotransplant". The patient underwent successful orthotopic liver transplantation 16 mo after admission to our centre. Our case report indicates the underrepresentation of morbidity associated with refractory ascites in the labMELD-based transplant allocation system, and it indicates the necessity of promptly applying for non-standard exception status to enable transplantation in patients with a severe clinical condition but low labMELD score. Our case highlights the fact that liver transplantation should be considered early in patients with non-resectable, symptomatic benign liver tumours.

15.
Neuropathology ; 35(2): 175-83, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25376227

RESUMO

We present two cases of atypical meningioma WHO grade II with a history of multiple local recurrences and late pulmonary metastases. Comparative cytogenetic analyses on 1p and 22q confirmed clonal origin of the primary intracranial meningiomas and the pulmonary metastases in both cases. These cases illustrate the importance of close neuroradiological follow-up to detect tumor recurrence in patients with atypical meningiomas WHO grade II even with clinically stable disease and should sensitize clinicians to late extracranial metastases of these tumors, especially to the lung. In an effort to elucidate common clinical features of metastatic meningiomas, especially to the lung, the literature was reviewed from 1995 to 2014, identifying a total of 45 published cases.


Assuntos
Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/secundário , Neoplasias Meníngeas/patologia , Meningioma/patologia , Recidiva Local de Neoplasia/patologia , Idoso , Cromossomos Humanos Par 1 , Cromossomos Humanos Par 22 , Análise Citogenética , Feminino , Humanos , Neoplasias Meníngeas/complicações , Neoplasias Meníngeas/genética , Meningioma/complicações , Meningioma/genética , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/complicações , Recidiva Local de Neoplasia/genética
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