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BACKGROUND: Primary tumor (PT) sidedness is an established prognostic marker in metastatic colorectal cancer (mCRC) and has a predictive impact on the efficacy of anti-epidermal growth factor receptor (anti-EGFR) antibody [monoclonal antibody (mAb)] in patients with RAS wild-type mCRC. This investigation focuses on patients with BRAFV600E-mutated (BRAFmt) mCRC and examines the efficacy of anti-EGFR mAbs in relation to primary tumor sidedness (PTS). PATIENT AND METHODS: This pooled analysis was carried out using individual patient data from five randomized studies in the first-line setting of mCRC. The population of interest was limited to patients with BRAFmt mCRC and known PTS. For analysis, treatment was stratified into two groups: those treated with anti-EGFR mAbs and those without. Dichotomous variables, such as overall response rate and objective response rate (ORR), were compared using chi-square or Fisher's exact test. Time-to-event endpoints [progression-free survival (PFS) and overall survival (OS)] were analyzed using the Kaplan-Meier method, log-rank test, and Cox regression. An interaction test was carried out via Cox regression. RESULTS: A total of 102 patients with BRAFmt mCRC were identified. The type of targeted therapy (anti-EGFR-based versus non-anti-EGFR) did not significantly impact the outcome. However, in patients with left-sided primary tumors, anti-EGFR mAb-based treatment, compared with non-anti-EGFR, was associated with a higher ORR (58% versus 34%; P < 0.01), trended toward improved PFS [hazard ratio (HR) 0.62; 95% confidence interval (CI) 0.34-1.13; P = 0.12], and demonstrated prolonged OS (HR 0.38; 95% CI 0.20-0.72; P < 0.01). In patients with right-sided primary tumors, anti-EGFR-based therapy had no effect on ORR (33% versus 36%; P > 0.99), induced inferior PFS (HR 1.97; 95% CI 1.12-3.47; P = 0.02), and trended toward a worse OS (HR 1.76; 95% CI 0.99-3.13; P = 0.05). CONCLUSION: This analysis suggests that PTS has predictive value for the efficacy of anti-EGFR mAb in the first-line treatment of BRAFmt mCRC.
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Background: Endometriosis is a chronic inflammatory oestrogen-dependent disease. It is characterised by elevated inflammatory markers in the peritoneal milieu with subsequent adhesiogenesis. Nowadays, excisional, and ablative surgeries are considered the main treatment of endometriosis, and adhesiolysis is being performed almost routinely during these procedures. Postoperative adhesion formation is a significant concern for many surgeons, especially as endometriosis patients are assumed to be predisposed to adhesiogenesis. In order to minimise adhesiogenesis after endometriosis surgery, the usage of different barrier methods have been discussed in the literature. Recent studies aim to investigate the effect of potato starch preparations on adhesion formation in endometriosis patients. Objectives: We aim to describe the findings of a second-look laparoscopy on patients who received a starch-based anti-adhesive agent. Materials and Methods: We present a retrospective case series that included the medical, surgical, and histopathologic data of three patients. Main outcome measures: Intraperitoneal adhesion formation and peritoneal inflammation. Results: All three patients had de-novo adhesions during the second-look laparoscopy. Pathological examination revealed noncaseating granulomatosis of the peritoneum in all patients. Conclusion: The use of potato starch-based agents as a peritoneal adhesion prophylaxis in laparoscopic endometriosis surgery could lead to granulomatous peritoneal inflammation. Correct application by avoiding powder remnants through complete rinsing and transformation to gel seems to be an important factor to avoid this adverse effect. What is new?: We aim to highlight that potato starch-based anti-adhesive agents similar to the one used in this study could be a cause of adhesiogenesis and peritoneal inflammation.
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BACKGROUND: Data on perioperative chemotherapy in resectable pancreatic ductal adenocarcinoma (rPDAC) are limited. NEONAX examined perioperative or adjuvant chemotherapy with gemcitabine plus nab-paclitaxel in rPDAC (National Comprehensive Cancer Network criteria). PATIENTS AND METHODS: NEONAX is a prospective, randomized phase II trial with two independent experimental arms. One hundred twenty-seven rPDAC patients in 22 German centers were randomized 1 : 1 to perioperative (two pre-operative and four post-operative cycles, arm A) or adjuvant (six cycles, arm B) gemcitabine (1000 mg/m2) and nab-paclitaxel (125 mg/m2) on days 1, 8 and 15 of a 28-day cycle. RESULTS: The primary endpoint was disease-free survival (DFS) at 18 months in the modified intention-to-treat (ITT) population [R0/R1-resected patients who started neoadjuvant chemotherapy (CTX) (A) or adjuvant CTX (B)]. The pre-defined DFS rate of 55% at 18 months was not reached in both arms [A: 33.3% (95% confidence interval [CI] 18.5% to 48.1%), B: 41.4% (95% CI 20.7% to 62.0%)]. Ninety percent of patients in arm A completed neoadjuvant treatment, and 42% of patients in arm B started adjuvant chemotherapy. R0 resection rate was 88% (arm A) and 67% (arm B), respectively. Median overall survival (mOS) (ITT population) as a secondary endpoint was 25.5 months (95% CI 19.7-29.7 months) in arm A and 16.7 months (95% CI 11.6-22.2 months) in the upfront surgery arm. This difference corresponds to a median DFS (mDFS) (ITT) of 11.5 months (95% CI 8.8-14.5 months) in arm A and 5.9 months (95% CI 3.6-11.5 months) in arm B. Treatment was safe and well tolerable in both arms. CONCLUSIONS: The primary endpoint, DFS rate of 55% at 18 months (mITT population), was not reached in either arm of the trial and numerically favored the upfront surgery arm B. mOS (ITT population), a secondary endpoint, numerically favored the neoadjuvant arm A [25.5 months (95% CI 19.7-29.7months); arm B 16.7 months (95% CI 11.6-22.2 months)]. There was a difference in chemotherapy exposure with 90% of patients in arm A completing pre-operative chemotherapy and 58% of patients starting adjuvant chemotherapy in arm B. Neoadjuvant/perioperative treatment is a novel option for patients with resectable PDAC. However, the optimal treatment regimen has yet to be defined. The trial is registered with ClinicalTrials.gov (NCT02047513) and the European Clinical Trials Database (EudraCT 2013-005559-34).
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Gencitabina , Neoplasias Pancreáticas , Humanos , Desoxicitidina , Estudos Prospectivos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/cirurgia , Neoplasias Pancreáticas/patologia , Albuminas , Paclitaxel , Terapia Neoadjuvante , Adjuvantes Imunológicos/uso terapêutico , Neoplasias PancreáticasAssuntos
COVID-19 , Arterite de Células Gigantes , Vacinas contra COVID-19 , Humanos , Necrose/etiologia , SARS-CoV-2 , VacinaçãoRESUMO
A 47-year-old male presented with dyspnoea and pulmonary nodules. He had longstanding asthma, chronic rhinosinusitis and a history of seizures, having been treated with valproic acid for years. A transbronchial biopsy and a bronchoalveolar lavage yielded a eosinophilic bronchitis and alveolitis without any malignant cells. The patient was then treated with oral corticosteroids for a few months, and the antiepileptic medication was switched to levetiracetam. Within a few months the dyspnoea improved and both the pulmonary nodules and the eosinophilia in the full blood count resolved. Eosinophilic lung diseases warrant a thorough investigation. Most likely, our patient suffers from eosinophilic granulomatosis with polyangiitis. As well, the eosinophilic lung disease might have been caused by valproic acid. Similar cases have been described in the literature.
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Asma , Síndrome de Churg-Strauss , Eosinofilia , Granulomatose com Poliangiite , Eosinofilia/diagnóstico , Eosinofilia/tratamento farmacológico , Humanos , Pulmão , Masculino , Pessoa de Meia-IdadeRESUMO
Polyps of the gastrointestinal tract encompass a variety of epithelial and non-epithelial tumour-like conditions. The most common polyps are epithelial lesions. In the upper gastrointestinal tract, reactive inflammatory changes and hyperplastic polyps dominate, whereas true neoplastic polyps, like adenomas, are much more common in the colorectum. In addition to neoplasias such as adenomas, non-neoplastic polyps such as hyperplastic polyps of the stomach may also be associated with an increased risk of malignancy. The risk of malignancy is determined by the histological subtype of polyp, as well as the size, presence and degree of dysplasia. The term "dysplasia" has been reintroduced for adenomas in the current 2019 World Health Organization (WHO) classification and replaces "intraepithelial neoplasia". A further change is the term "sessile serrated lesion" with and without dysplasia, which was formerly known as sessile serrated adenoma.
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Adenoma/patologia , Trato Gastrointestinal/fisiopatologia , Hiperplasia/patologia , Pólipos do Colo , Neoplasias Colorretais , HumanosRESUMO
PURPOSE: In mCRC, disease dynamics may play a critical role in the understanding of long-term outcome. We evaluated depth of response (DpR), time to DpR, and post-DpR survival as relevant endpoints. METHODS: We analyzed DpR by central review of computer tomography images (change from baseline to smallest tumor diameter), early tumor shrinkage (≥ 20% reduction in tumor diameter at first reassessment), time to DpR (study randomization to DpR-image), post-DpR progression-free survival (pPFS = DpR-image to tumor progression or death), and post-DpR overall survival (pOS = DpR-image to death) with special focus on BRAF status in 66 patients and primary tumor site in 86 patients treated within the VOLFI-trial, respectively. RESULTS: BRAF wild-type (BRAF-WT) compared to BRAF mutant (BRAF-MT) patients had greater DpR (- 57.6% vs. - 40.8%, p = 0.013) with a comparable time to DpR [4.0 (95% CI 3.1-4.4) vs. 3.9 (95% CI 2.5-5.5) months; p = 0.8852]. pPFS was 6.5 (95% CI 4.9-8.0) versus 2.6 (95% CI 1.2-4.0) months in favor of BRAF-WT patients (HR 0.24 (95% CI 0.11-0.53); p < 0.001). This transferred into a significant difference in pOS [33.6 (95% CI 26.0-41.3) vs. 5.4 (95% CI 5.0-5.9) months; HR 0.27 (95% CI 0.13-0.55); p < 0.001]. Similar observations were made for patients stratified for primary tumor site. CONCLUSIONS: BRAF-MT patients derive a less profound treatment response compared to BRAF-WT patients. The difference in outcome according to BRAF status is evident after achievement of DpR with BRAF-MT patients hardly deriving any further disease control beyond DpR. Our observations hint towards an aggressive tumor evolution in BRAF-MT tumors, which may already be molecularly detectable at the time of DpR.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Mutação , Proteínas Proto-Oncogênicas B-raf/genética , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Camptotecina/administração & dosagem , Camptotecina/análogos & derivados , Neoplasias Colorretais/enzimologia , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Progressão da Doença , Feminino , Fluoruracila/administração & dosagem , Humanos , Leucovorina/administração & dosagem , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Compostos Organoplatínicos/administração & dosagem , Panitumumabe/administração & dosagem , Resultado do Tratamento , Proteínas ras/genéticaRESUMO
Intraoperative frozen sections can significantly improve the results of numerous visceral surgical operations. For this a close cooperation between surgery and pathology is a basic prerequisite. The main indications are the diagnostics of unclear intraoperative findings and the assessment of resection margins. Just as in any other procedure, there are also limiting factors to be considered in frozen section examinations.
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Secções Congeladas , Cuidados Intraoperatórios , Humanos , Margens de Excisão , Estudos RetrospectivosRESUMO
A 65-year-old German woman was admitted to a hospital emergency department with progressively worsening back pain. She died a few days later due to septic shock, the very rare cause of death was revealed by an autopsy.This case report emphasizes the importance of clinical autopsy especially against the background of hospital quality management.
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Causas de Morte , Choque Séptico/complicações , Idoso , Autopsia , Dor nas Costas/complicações , Evolução Fatal , Feminino , HumanosRESUMO
In pathological diagnostics, monoclonal antibodies (mAb) are mainly used for immunhistochemical analysis. After an initial histological evaluation, a precise panel of antibodies is selected in order to stain the slides by using an indirect immune method. The most frequent issues include localisation of the primary tumor in cases of metastases, determination of undifferentiated tumors, subtyping of lympho-proliferative diseases and soft tissue tumors, as well as the assessment of proliferation via Ki-67. Increasing importance in mAb-based diagnostics is attributed to the analysis of predictive biomarkers such as hormone receptors, mismatch repair proteins (MMR) and programmed death ligand 1 (PD-L1). Their evaluation is performed by using different scores, which the clinical physician needs to be aware of due to their direct therapeutic implications.
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Anticorpos Monoclonais , Antineoplásicos Imunológicos , Biomarcadores Tumorais/metabolismo , Reparo de Erro de Pareamento de DNA , Imuno-Histoquímica/métodos , Neoplasias/patologia , Antígeno B7-H1/genética , Antígeno B7-H1/metabolismo , Neoplasias/genética , Neoplasias/metabolismoRESUMO
N-methyl-D-aspartate receptor (NMDAR) encephalitis is a rare antibody-mediated autoimmune encephalitis often associated with an ovarian teratoma in adolescent females. Here we present a 17-year-old girl with only and unusual psychiatric symptoms as part of her NMDAR encephalitis in combination with a very small ovarian teratoma suspected by magnetic resonance (MR) imaging and finally histologically confirmed. We further review the literature of NMDAR encephalitis in combination with an ovarian teratoma and discuss the recommended radiological workup in children with a suspected ovarian tumor.
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Encefalite Antirreceptor de N-Metil-D-Aspartato/complicações , Ansiedade/complicações , Depressão/complicações , Transtornos Dissociativos/complicações , Neoplasias Ovarianas/complicações , Teratoma/complicações , Adolescente , Encefalite Antirreceptor de N-Metil-D-Aspartato/diagnóstico por imagem , Feminino , Humanos , Imageamento por Ressonância Magnética , Neoplasias Ovarianas/diagnóstico por imagem , Teratoma/diagnóstico por imagemRESUMO
BACKGROUND: Although complete mesocolic excision has been performed for 10 years there remains no published prospective data. The lack of a classification which includes completeness of mesocolic tissue removal as well as plane of surgery contributes to the problem of comparing studies. The aim of the present study was to develop such a classification for right hemicolectomy. METHODS: In a prospective, non-randomized trial we collected specimens of right hemicolectomies from 38 German hospitals between February 2012 and October 2016. The degree of radicality of resection was reported. Photographs were taken of the specimens. After screening the images it became apparent that the specimens could be divided into four main groups according to the degree of missing mesocolic tissue, and three subgroups reflecting the plane of surgery. RESULTS: Of 1373 patients 1097 images were available. Grading was possible in 1077 (98.2%). Distribution was Type 0 (best) 38.6%, Type I 43.3%, Type II 8.5%, Type III (poorest) 7.8%. Surgery was considered to be in a suboptimal plane of surgery in 15.2% overall, highest in Type III (37%) and lowest in Type 0 (7.8%, p < 0.001). CONCLUSIONS: The proposed classification may be a relevant tool for the further investigation of CME for right colon cancer because it allows us to differentiate the aspects of lymphadenectomy and the preservation of the integrity of the mesocolon.
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Colectomia/classificação , Neoplasias do Colo/cirurgia , Mesocolo/cirurgia , Idoso , Idoso de 80 Anos ou mais , Colectomia/métodos , Neoplasias do Colo/patologia , Feminino , Humanos , Excisão de Linfonodo/classificação , Excisão de Linfonodo/métodos , Masculino , Pessoa de Meia-Idade , Ensaios Clínicos Controlados não Aleatórios como Assunto , Estudos ProspectivosRESUMO
BACKGROUND: In Germany, asbestos-related diseases (asbestosis, lung cancer, mesothelioma) are recognised and compensated occupational diseases. The histologic diagnosis of mesothelioma is sometimes a challenge; additional immunohistochemical and molecular methods are needed. With lung dust analysis, the current asbestos fibre burden of the lung is measured (biomonitoring). Identification of grade I asbestosis (minimal asbestosis) requires directed histological examinations with up to 400-fold magnification, additional iron staining and possibly in connection with a lung dust analysis. OBJECTIVES: Demonstration of current pathologic diagnostics in association with mesothelioma and lung dust analysis. MATERIALS AND METHODS: Analysis of routine data from the German Mesothelioma Register. RESULTS: Contrary to reactive mesothelial hyperplasia, malignant mesotheliomas have a nuclear BAP1 loss-of-expression in up to 66% of cases. For differential diagnosis between reactive versus malignant, a p16-FISH test may be helpful. BAP1 loss-of-expression and p16-deletion are independent markers. Evaluation of the dataset of the German Mesothelioma Register of patients with repeated tissue sampling proves the detection of asbestos fibres at the same level even after 40 years. The asbestos fibre burden in the human lung remains stable over this long period of time. In the electron microscopic analysis, white asbestos was predominantly found. CONCLUSIONS: The well-known and industrially appreciated characteristics of asbestos fibres (in ancient á¼σßεστος asbestos "imperishable") as biopersistent have also been experimentally confirmed in human lungs.
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Amianto , Neoplasias Pulmonares , Mesotelioma , Exposição Ocupacional , Alemanha , Humanos , Pulmão , Proteínas Supressoras de Tumor , Ubiquitina TiolesteraseRESUMO
Early stage cancer of the bile duct system is still difficult to diagnose. In cases of suspect lesions a stepwise diagnostic procedure consisting of computed tomography (CT), magnetic resonance imaging (MRI) with MR cholangiography (MRC) and possibly endoscopic retrograde cholangiopancreatography (ERCP) with brush cytology should immediately be carried out. If there is a sufficient suspicion for premalignancy or early stage cancer the indications for surgical intervention should clearly be defined. Only resection can lead to a decrease in the recurrence rate and a better long-term outcome. If the patient is in a functionally nonresectable condition the possibility of liver transplantation should be considered.
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Neoplasias dos Ductos Biliares , Colangiopancreatografia Retrógrada Endoscópica , Lesões Pré-Cancerosas , Neoplasias dos Ductos Biliares/diagnóstico por imagem , Ductos Biliares , Colangiografia , Humanos , Imageamento por Ressonância Magnética , Recidiva Local de Neoplasia , Lesões Pré-Cancerosas/diagnóstico por imagemRESUMO
Malignant mesotheliomas are rare and aggressive tumours arising from mesothelial cells of the pleura and peritoneum. Infrequent sites of origin are the pericardium and tunica vaginalis testis. More than 80% of mesotheliomas are localized in the pleura. Men are more frequently affected than women. The median age is >60 years. Asbestos exposure is the best known aetilogical risk factor and is reported in 54-90% of patients. In Germany, malignant mesotheliomas caused by occupational asbestos exposure are compensated as occupational disease since 1977. Several neoplastic and non-neoplastic lesions like metastasis, sarcomas, lymphomas or pleuritis with reactive mesothelial proliferation have to be distinguished from malignant mesotheliomas. Especially, the pathohistological differentiation between atypical reactive mesothelial proliferation from malignant mesothelioma is a diagnostic challenge.