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1.
Diabetes Obes Metab ; 24(4): 684-692, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-34957654

RESUMO

AIM: To investigate whether upper gastrointestinal (GI) disease has any effect on the exposure of oral semaglutide, an important consideration given that its absorption occurs primarily in the stomach. MATERIALS AND METHODS: In an open-label, parallel-group trial (NCT02877355), subjects aged 18-80 years with type 2 diabetes with mild-to-moderate upper GI disease (N = 36; chronic gastritis [n = 5], gastroesophageal reflux disease [n = 8], and both [n = 23]) or without upper GI disease (N = 19) received oral semaglutide 3 mg once daily for 5 days, followed by 7 mg for 5 days. The primary and key supportive endpoints were the area under the semaglutide plasma concentration-time curve (AUC) from 0 to 24 hours after last trial product administration on day 10 (AUC0-24h,day10 ) and the maximum semaglutide plasma concentration (Cmax,day10 ), respectively. RESULTS: Semaglutide exposure was not statistically significantly different between subjects with and without upper GI disease. Estimated group ratios (subjects with/without upper GI disease) were 1.18 (95% confidence interval [CI], 0.80, 1.75) for AUC0-24h,day10 and 1.16 (95% CI, 0.77, 1.76) for Cmax . Time to Cmax and semaglutide half-life were similar in subjects with and without upper GI disease. Oral semaglutide was well tolerated; all adverse events were mild-to-moderate, with no withdrawals because of adverse events. CONCLUSIONS: There was no significant difference in exposure to oral semaglutide in subjects with or without upper GI disease, hence no dose adjustment is required.


Assuntos
Diabetes Mellitus Tipo 2 , Gastroenteropatias , Administração Oral , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Diabetes Mellitus Tipo 2/induzido quimicamente , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Gastroenteropatias/induzido quimicamente , Gastroenteropatias/tratamento farmacológico , Peptídeos Semelhantes ao Glucagon , Humanos , Hipoglicemiantes , Pessoa de Meia-Idade , Adulto Jovem
2.
Chirurg ; 93(5): 453-460, 2022 May.
Artigo em Alemão | MEDLINE | ID: mdl-35290470

RESUMO

The macroscopic and microscopic assessments of pancreatic cancer resection specimens belong to the standard repertoire of any department of pathology. In recent years standards have been developed regarding both macroscopic and microscopic assessments, which are laid down in international and national guidelines and classifications and are regularly updated. In this way the reporting of results and interdisciplinary communication are facilitated. These classifications and guidelines are influenced by current studies and the data from them provide information on which histopathological factors are particularly relevant for the prognosis and treatment. Due to the increasing use of neoadjuvant therapy the assessment of tumor regression in histopathological specimens is also gaining in importance. Finally, individual targeted treatments are also now available for pancreatic cancer, which require extended molecular pathological diagnostics.


Assuntos
Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Carcinoma Ductal Pancreático/patologia , Carcinoma Ductal Pancreático/cirurgia , Humanos , Terapia Neoadjuvante , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/cirurgia , Prognóstico
3.
Artigo em Inglês | MEDLINE | ID: mdl-35270381

RESUMO

BACKGROUND: Hypoglossal nerve palsy (HNP) is rather common as a neurological disease. However, as an isolated nerve palsy it is an exceedingly rare phenomenon and points at local pathologies along the peripheral course of the nerve. In this communication we report a granular cell tumor (GCT) arising in the submandibular segment of the hypoglossal nerve. CASE-REPORT: Spontaneous isolated HNP was recognized in a female patient. First line MR-imaging identified a clivus-chordoma. However, involvement of the hypoglossal nerve was highly unlikely according to MR-findings. Finally, ultrasonographic investigation revealed a small submandibular mass which, at histological examination, turned out to be a granular cell tumor arising within the hypoglossal nerve. CONCLUSIONS: This is the report of an extremely rare GCT originating within the 12th cranial nerve. The case illustrates that isolated motoric cranial nerve palsy may result from this rare tumor entity. This report also points out the diagnostic value of a simple ultrasonographic investigation to depict pathologic lesions of the submandibular space.


Assuntos
Tumor de Células Granulares , Doenças do Nervo Hipoglosso , Feminino , Tumor de Células Granulares/diagnóstico , Tumor de Células Granulares/diagnóstico por imagem , Humanos , Nervo Hipoglosso/patologia , Doenças do Nervo Hipoglosso/diagnóstico , Doenças do Nervo Hipoglosso/etiologia , Doenças do Nervo Hipoglosso/patologia , Imageamento por Ressonância Magnética , Paralisia
4.
Hepatobiliary Surg Nutr ; 11(1): 25-37, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35284530

RESUMO

Background: Aberrant right hepatic arteries (aRHA) are frequently encountered during pancreaticoduodenectomy (PD). Their effects on surgical morbidity and resection margin are still debated. This study aimed to compare the short term and long term outcomes in patients with and without aRHA. Methods: A single-center retrospective analysis of 353 consecutive PD during a 5-year period was done. The type of arterial supply was determined preoperatively by CT and confirmed at surgery. Hiatt types III-VI included some type of aRHA and comprised the study group. Hiatt types I and II were considered irrelevant for PD and used as controls. Primary endpoints were the rates of major postoperative complications and the rate of R0-resection in cases of malignant disease. Secondary endpoints included duration of surgery, postoperative stay, number of harvested lymph nodes and survival in patients with pancreatic cancer. Own results were compared to existent data using a systematic review of the literature. Results: No aRHA had to be sacrificed or reconstructed. Surgical morbidity and specific complications such as post-pancreatectomy hemorrhage (PPH), pancreatic fistula and bile leak were the same in patients with and without aRHA. There was no significant difference in operative time, blood loss, length of ICU- and hospital stay. Patients with malignancy had similar high rates of R0-resection and identical number of harvested lymph nodes. Survival of patients with pancreatic cancer was not affected by aRHA. Conclusions: aRHA may be preserved in virtually all cases of PD for resectable pancreatic head lesions without increasing surgical morbidity and without compromising oncological radicality in patients with cancer, provided the variant anatomy is being recognised on preoperative CT and a meticulous surgical technique is used.

5.
Cancers (Basel) ; 14(3)2022 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-35158793

RESUMO

Primary tumor sidedness (left vs. right) has prognostic and predictive impact on anti-EGFR agent efficacy and thus management of metastatic colorectal cancer (mCRC). This analysis evaluates the relevance of primary tumor location (PTL) in RAS/BRAF wild-type mCRC patients, when dividing the colorectal frame into six segments. This pooled analysis, performed on a single-patient basis of five randomized first-line therapy trials, evaluates the impact of exact PTL classification on baseline characteristics, prognosis and prediction of anti-EGFR antibody efficacy by chi-square and log-rank tests, the Kaplan-Meier method, Cox and logistic regressions. The PTL was significantly associated with metastatic spread: liver (p = 0.001), lung (p = 0.047), peritoneal (p < 0.001) and lymph nodes (p = 0.048). A multivariate analysis indicated an impact on anti-EGFR agent efficacy in terms of overall survival depending on the exact primary tumor location: from detrimental in caecal (HR 2.63), rather neutral effects in the ascending colon (HR 1.24), right flexure/transverse colon (HR 0.99) and left flexure/descending colon (HR 0.91) to clear benefit in sigmoid (HR 0.71) and rectal (HR 0.58) primaries. Exact primary tumor location affects anti-EGFR antibody efficacy in a rather continuous than a dichotomous fashion in RAS/BRAF wild-type mCRC patients. This perspective might help to support clinical decisions when anti-EGFR antibodies are considered.

6.
Trials ; 23(1): 173, 2022 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-35193638

RESUMO

BACKGROUND: Ulcerative colitis (UC) is a chronic inflammatory bowel disease with significant morbidity and mortality. Although the precise cause remains unknown, disturbances in the intestinal microbial community have been linked to its pathogenesis. Randomized controlled trials in UC and relapsing Clostridioides difficile infection (CDI) have established fecal microbiota (FM) transfer (FMT) as an effective therapy. In this context, preliminary results indicated that the transfer of sterile fecal microbiota filtrates (<0.2 µm; FMF, FMFT) of donor stool also drives gastrointestinal microbiota changes and eliminates symptoms in CDI patients. However, along with the success of FMT, regulatory agencies issued safety alerts following reports of serious adverse events due to transmission of enteric pathogens through FMT. To reduce this risk, we established an extensive test protocol for our donors and quarantine regulations for the produced capsules, but alternative concepts are desirable. METHODS: Our project is a randomized, controlled, longitudinal, prospective, three-arm, multicenter, double-blind study to determine the safety and efficacy of repeated long-term, multi-donor FM or FMF transfers compared to placebo using oral, frozen capsules in 174 randomized patients with mild to moderate active UC. The primary outcome will be clinical remission at week 12. DISCUSSION: This proposal aims to examine (a) the efficacy of encapsulated transfer of FM and FMF as a therapy for mild to moderate UC, (b) the short- and long-term safety of FMT and FMFT in patients with UC, and (c) the microbial and immunologic changes that occur after FMT and FMFT to help understand how and why it affects inflammatory bowel disease. TRIAL REGISTRATION: ClinicalTrials.gov NCT03843385 . DRKS (Deutsches Register für Klinische Studien) DRKS00020471.


Assuntos
Colite Ulcerativa , Colite Ulcerativa/diagnóstico , Colite Ulcerativa/terapia , Método Duplo-Cego , Transplante de Microbiota Fecal/efeitos adversos , Transplante de Microbiota Fecal/métodos , Fezes , Humanos , Estudos Multicêntricos como Assunto , Estudos Prospectivos , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento
7.
Cancer Med ; 11(8): 1735-1744, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35146948

RESUMO

BACKGROUND: Colon cancer (CC) is a disease of elderly patients (pts.) with a median age of 73 years (yrs.). Lack of data about the effects of adjuvant chemotherapy (ACT) is caused by underrepresentation of this clinically relevant cohort in interventional trials. We analyzed real-world data from the German CPP registry with regard to a possible benefit of ACT in elderly (70+ yrs.) versus younger pts. (50 to <70 yrs.) taking cause-specific deaths into account. METHODS: We analyzed the effect of age and ACT on overall survival (OS) and cause-specific death of stage III pts. using Cox regression. RESULTS: In total, 1558 pts. were analyzed and follow-up was 24.6 months. 62.6% of the elderly received ACT whereas 91.1% of younger pts. (p < 0.001). Oxaliplatin combinations were significantly less often given to older than younger pts. (38.8% vs. 88.9%; p < 0.001). Mean Charlson comorbidity score was significantly lower in pts. that received ACT (0.61) than in those without ACT (1.16; p < 0.001). ACT was an independent positive prognostic factor for cancer-related death in elderly pts. even in pts. 75+ yrs. No significant difference in the effect of ACT could be observed between age groups (interaction: cancer-specific death HR = 1.7948, p = 0.1079; death of other cause HR = 0.7384, p = 0.6705). CONCLUSION: ACT was an independent positive prognostic factor for OS. There may be a cohort of elderly with less co-morbidities who benefit from ACT.


Assuntos
Neoplasias do Colo , Idoso , Quimioterapia Adjuvante , Neoplasias do Colo/tratamento farmacológico , Humanos , Oxaliplatina/uso terapêutico , Pirazinas , Sistema de Registros
8.
Pathologe ; 43(2): 157-166, 2022 Mar.
Artigo em Alemão | MEDLINE | ID: mdl-35171314

RESUMO

Nonalcoholic fatty liver disease (NAFLD) is one of the most frequent chronic liver diseases with a rising incidence in industrial countries. This is accompanied by an increased prevalence for NAFLD-associated liver cirrhosis and an increased risk for developing hepatocellular carcinoma. The current gold standard in the diagnostics is a liver biopsy. The histopathological evaluation is performed through semiquantitative scoring. To optimize the standardization and quantification of the existing scoring systems, in the coming years procedures with artificial intelligence, such as deep learning models could be used. Fields of application could be the supplementation of conventional histopathological diagnostics, the identification of new predictive parameters for estimating the prognosis and the prediction of a possible response to treatment.


Assuntos
Neoplasias Hepáticas , Hepatopatia Gordurosa não Alcoólica , Inteligência Artificial , Biópsia , Humanos , Fígado/patologia , Cirrose Hepática/patologia , Neoplasias Hepáticas/patologia , Hepatopatia Gordurosa não Alcoólica/patologia
9.
J Surg Oncol ; 125(2): 134-144, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34634138

RESUMO

BACKGROUND: Secondary lymphedema is a leading sequela of cancer surgery and radiotherapy. The microsurgical transfer of lymph node flaps (LNFs) to affected limbs can improve the symptoms. The intra-abdominal cavity contains an abundant heterogenic source. The aim of this study is to aid selection among intra-abdominal LNFs. METHODS: Eight LNFs were harvested in a microsurgical fashion at five sites in 16 cadavers: gastroepiploic, jejunal, ileal, ileocolic, and appendicular. These flaps were compared regarding size, weight, arterial diameter, and lymph node (LN) count after histologic verification. RESULTS: One hundred and sixteen flaps were harvested. The exposed area correlated with the flap weight and volume (r2 = 0.86, r = 0.9). While gastroepiploic LNFs (geLNFs) showed the highest median weight of 99 ml, the jejunal LNFs (jLNFs) had the highest density with 3.8 LNs per 10 ml. The most reliable jLNF was 60 cm from the ligament of Treitz. Three or more LNs were contained in 94% of the jejunal, 88% of the ileal/ileocolic, and 63% of the omental LNs. The ileocolic LNF had the largest arterial diameter of 3 mm, yet the smallest volume. CONCLUSIONS: jLNF and ileal LNF provide a reliable, high LN density for simultaneous, smaller recipient sites. geLNFs are more suitable for larger recipient sites.


Assuntos
Linfonodos/transplante , Linfedema/cirurgia , Retalhos Cirúrgicos , Abdome/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Linfonodos/anatomia & histologia , Masculino , Pessoa de Meia-Idade , Doadores de Tecidos , Coleta de Tecidos e Órgãos
10.
Scand J Gastroenterol ; 57(1): 22-30, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34618623

RESUMO

OBJECTIVE: The aim of this study was to characterize duodenal mast cell (MC) and eosinophil (EO) numbers, their distribution within the lamina propria and possible impact on disease severity of paediatric celiac patients compared to children without celiac disease (CD). METHODS: We analysed duodenal samples of 215 children (109 CD, 106 controls) who underwent esophagogastroduodenoscopy from 2010 to 2018. After immunohistochemical staining, average MC and EO counts were histologically examined in ten high-power-fields. Additionally, cell-distribution within the lamina propria was analysed. Possible influence of relevant clinical parameters was evaluated. STATISTICS: Student's-t-test, Mann-Whitney U-test, Chi-square-test, ANOVA, significance-level <.05. Trial registration-number: DRKS00024669. RESULTS: MC-density was higher in CD-patients compared to the control-group (23.7 (±12.1)/HPF versus 19.7 (±9.1)/HPF; p = .008), varying in number interindividually. Eosinophils were also increased in the duodenum of celiac patients (23.3 (±9.3)/HPF versus 12.2 (±6.3)/HPF; p= <.001). MCs were distributed more often homogenously in all parts of CD lamina propria (44 biopsies (40.4%), residing more distant from the intestinal lumen in controls (0 biopsies with homogenous distribution-pattern (0%); p= <.001). Regarding EOs no polarity was observable. Atopic diseases did not occur significantly more often in patients with elevated EO-counts. CONCLUSION: MC- and EO-numbers were increased in the duodenum of CD-patients and MCs showed a different distribution-pattern in the lamina propria of celiac patients. These findings support the concept that both cell-types contribute to disease-pathogenesis. However, functional studies highlighting both cell-types' and their mediators' role regarding mucosal alterations during the course of the inflammatory process in celiac patients are needed. TRIAL REGISTRATION NUMBER AND URL: DRKS00024669; https://www.drks.de/drks_web/.


Assuntos
Doença Celíaca , Eosinófilos , Biópsia , Doença Celíaca/patologia , Criança , Duodeno/patologia , Humanos , Mucosa Intestinal/patologia , Contagem de Leucócitos , Mastócitos
11.
Chirurg ; 93(2): 115-122, 2022 Feb.
Artigo em Alemão | MEDLINE | ID: mdl-34613440

RESUMO

Histopathologic evaluation of tumors after neoadjuvant therapy is performed by tumor regression grading (TRG) systems, which reflect the proportion of vital residual primary tumor in relation to the previous total tumor. The World Health Organization (WHO) tumor grading is replaced by TRG in tumor classification. The histopathological work-up of a tumor is based on the criteria of the TNM classification even after neoadjuvant therapy. A uniform TRG does not exist. For various tumors TRGs based on the tumor entity have been established, consisting of a 3-stage or 5­stage grading system. Complete histopathological tumor regression is only present if no vital tumor cells are detectable in the histopathological examination of the primary surgical specimens (primary tumor and accompanying locoregional lymph nodes) and there are no distant metastases.


Assuntos
Linfonodos , Terapia Neoadjuvante , Gradação de Tumores , Estadiamento de Neoplasias , Prognóstico , Indução de Remissão , Estudos Retrospectivos , Resultado do Tratamento
12.
Clin Hemorheol Microcirc ; 80(4): 423-436, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34842182

RESUMO

Liver cirrhosis is an established high-risk factor for HCC and the majority of patients diagnosed with HCC have cirrhosis. However, HCC also arises in non-cirrhotic livers in approximately 20 %of all cases. HCC in non-cirrhotic patients is often clinically silent and surveillance is usually not recommended. HCC is often diagnosed at an advanced stage in these patients. Current information about HCC in patients with non-cirrhotic liver is limited. Here we review the current knowledge on epidemiology, clinical features and imaging features of those patiens.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Hepatopatia Gordurosa não Alcoólica , Carcinoma Hepatocelular/complicações , Carcinoma Hepatocelular/patologia , Humanos , Fígado/diagnóstico por imagem , Fígado/patologia , Cirrose Hepática/complicações , Neoplasias Hepáticas/patologia , Hepatopatia Gordurosa não Alcoólica/complicações
13.
Artigo em Inglês | MEDLINE | ID: mdl-35501497

RESUMO

PURPOSE: Primary breast sarcomas are extraordinary rare, in particular undifferentiated pleomorphic sarcoma (UPS). UPS with neoplastic fever (UPS-NF) of the breast has not been reported yet. Here, we present an extended UPS-NF of the breast including its comprehensive molecular workup. METHODS: A 58-year-old female presented with general malaise, fever spikes, weight loss, and a massively swollen left breast. C-reactive protein and blood leucocytes were significantly increased. However, repeated blood cultures and smears were all sterile. Histopathology of the abscess-forming tumor revealed an undifferentiated malignancy with numerous of tumor giant cells as well as spindle-shaped cells with nuclear pleomorphism and hyperchromasia. Immunohistochemistry demonstrated partial, patchy desmin staining and weak heterogonous neuron-specific enolase immunoreactivity of tumor cells, but a focal staining for Melan-A. RESULTS: Neither common melanoma driver mutations nor an ultraviolet mutational signature was detected by whole genome sequencing. Using FISH and RT-PCR we also excluded translocations characteristic for clear cell sarcoma. Thus, the diagnosis of inflammatory UPS-NF of the breast was considered highly probable. Despite a complete mastectomy, the tumor recurred after only three months. This recurrence was treated with a combination of ipilimumab and nivolumab based on the primary tumor's TPS score for PD-L1 of 30%. After an initial response, however, the tumor was progressive again. CONCLUSION: We describe here the first case of UPS-NF of the breast, which shows great clinical and histopathologic resemblances to previously reported UPS-NF of other anatomic localizations.

14.
Medicine (Baltimore) ; 100(52): e28205, 2021 Dec 30.
Artigo em Inglês | MEDLINE | ID: mdl-34967354

RESUMO

INTRODUCTION: Persistent systemic inflammation is considered to be predictive for future cardiovascular events. Here, in a patient with pyelonephritis of his failed renal allograft, consecutive coronary angiograms proved that coronary artery disease progressed within 3 weeks, when infection was uncontrolled. PATIENT CONCERNS: A 52-year-old male type 2 diabetic with a failed renal allograft suffering from hematuria, leukocyturia, and chest pain at rest was hospitalized. DIAGNOSES: An acute coronary syndrome in presence of pyelonephritis was diagnosed. Besides pyelonephritis, the histological examination of the kidney transplant revealed signs of chronic rejection and the presence of a renal cell carcinoma in situ. INTERVENTIONS: A percutaneous coronary intervention was performed, and an elective surgery for allograft removal was scheduled. However, within 5 weeks after discharge, two more surges of infection coincided with episodes of unstable angina. OUTCOMES: Once the renal allograft has been removed, systemic inflammation was contained. The patient was not re-hospitalized for acute-coronary syndrome within the next 12 months. CONCLUSION: Surges of systemic inflammation due to infection were paralleled by instability of coronary plaques as documented by repeat coronary angiograms.


Assuntos
Síndrome Coronariana Aguda/diagnóstico , Inflamação/etiologia , Transplante de Rim/efeitos adversos , Pielonefrite/diagnóstico , Síndrome Coronariana Aguda/complicações , Aloenxertos , Humanos , Masculino , Pessoa de Meia-Idade , Intervenção Coronária Percutânea , Pielonefrite/complicações
15.
BMJ Case Rep ; 14(12)2021 Dec 17.
Artigo em Inglês | MEDLINE | ID: mdl-34920999

RESUMO

Vaping may lead to spontaneous pneumothorax, but there are few published reports on this phenomenon. We present a case of vaping-related pneumothorax and make recommendations for structured reporting of this emerging cause for pneumothorax. A normal-weight 34-year-old male presented to our emergency department with dyspnoea and back pain increasing over 24 hours. Chest X-ray showed a large right-sided pneumothorax. Three years ago, he had quit smoking cigarettes and switched to vaping. CT scan revealed bullae, and the patient received apical lung resection. Histology revealed mild alveolitis. Vaping is an emerging cause of lung injury. This report demonstrates a potential association between vaping and pneumothorax. However, structured reporting and future research are needed to establish a definitive (or causal) relationship between vaping and pneumothorax.


Assuntos
Sistemas Eletrônicos de Liberação de Nicotina , Pneumotórax , Vaping , Adulto , Humanos , Masculino , Pneumotórax/diagnóstico por imagem , Pneumotórax/etiologia , Vaping/efeitos adversos
16.
Artigo em Inglês | MEDLINE | ID: mdl-34772609

RESUMO

BACKGROUND: Guidance regarding adjuvant treatment decisions in stage II colorectal cancer (CRC) remains uncertain due to lack of predictive clinical or molecular markers. Recently, postoperative circulating tumour (ct)DNA has been demonstrated to be a strong prognostic marker in early colon cancer. PATIENTS AND METHODS: CIRCULATE enrols patients with stage II microsatellite stable CRC in Germany (AIO) and Austria (ABCSG). Within the AIO, screening is supported by ColoPredict Plus 2.0, a molecular registry, and screening platform for interventional trials. Patient-specific mutations are centrally analysed by next generation sequencing in the resected primary tumour. A postoperative plasma sample is subsequently screened for the specific mutation(s). ctDNA positive (ctDNApos) patients are randomised (2:1) chemotherapy (capecitabine, oxaliplatin added an investigator's choice) or to follow-up (control group). ctDNA negative (ctDNAneg) patients are randomised (1:4) to be followed-up within CIRCULATE (control group) or outside the trial. Patients in the control group remain blinded to the ctDNA results. The primary objective is to compare disease free survival (DFS) of ctDNApos patients with chemotherapy or control. To demonstrate a treatment effect with a hazard ratio of 0.617 (3-year DFS rates 42.5% vs. 25%), 231 ctDNApos and estimated 2079 ctDNAneg patients are randomised. Secondary aims include to compare overall survival and DFS in the ctDNApos and ctDNAneg patient cohorts and ctDNA kinetics. CONCLUSION: The CIRCULATE trial may establish ctDNA for adjuvant treatment decision in stage II colon cancer - and with the secondary objectives - support a ctDNA guided follow up in colon cancer stage II and beyond.

17.
Brain Commun ; 3(4): fcab238, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34708206

RESUMO

Proteasome inhibition with bortezomib has been reported to exert an immunomodulatory action in chronic autoimmune neuropathies. However, bortezomib used for the treatment of multiple myeloma induces a painful toxic polyneuropathy at a higher concentration. Therefore, we addressed this controversial effect and evaluated the neurotoxic and immunomodulatory mode of action of bortezomib in experimental autoimmune neuritis. Bortezomib-induced neuropathy was investigated in Lewis rats using the von Frey hair test, electrophysiological, qPCR and histological analyses of the sciatic nerve as well as dorsal root ganglia outgrowth studies. The immunomodulatory potential of bortezomib was characterized in Lewis rats after experimental autoimmune neuritis induction with P253-78 peptide. Clinical, electrophysiological, histological evaluation, von Frey hair test, flow cytometric and mRNA analyses were used to unravel the underlying mechanisms. We defined the toxic concentration of 0.2 mg/kg bortezomib applied intraperitoneally at Days 0, 4, 8 and 12. This dosage induces a painful toxic neuropathy but preserves axonal regeneration in vitro. Bortezomib at a concentration of 0.05 mg/kg significantly ameliorated experimental autoimmune neuritis symptoms, improved experimental autoimmune neuritis-induced hyperalgesia and nerve conduction studies, and reduced immune cell infiltration. Furthermore, proteasome inhibition induced a transcriptional downregulation of Nfkb in the sciatic nerve, while its inhibitor Ikba (also known as Nfkbia) was upregulated. Histological analyses of bone marrow tissue revealed a compensatory increase of CD138+ plasma cells. Our data suggest that low dose bortezomib (0.05 mg/kg intraperitoneally) has an immunomodulatory effect in the context of experimental autoimmune neuritis through proteasome inhibition and downregulation of nuclear factor 'kappa-light-chain-enhancer' of activated B-cells (NFKB). Higher bortezomib concentrations (0.2 mg/kg intraperitoneally) induce sensory neuropathy; however, the regeneration potential remains unaffected. Our data empathizes that bortezomib may serve as an attractive treatment option for inflammatory neuropathies in lower concentrations.

18.
Curr Oncol ; 28(5): 3316-3322, 2021 08 27.
Artigo em Inglês | MEDLINE | ID: mdl-34590599

RESUMO

There exist relatively sparse and conflicting data on high-level microsatellite instability (MSI-H) and deficient mismatch repair (dMMR) in cutaneous malignancies. We aimed to determine the expression profiles of MMR proteins (MSH2, MSH6, MLH1, and PMS2) in different progression stages of cutaneous squamous cell carcinoma (cSCC, 102 patients in total) by immunohistochemistry, and search for MSI-H in patients with low-level MMR or dMMR using multiplex-PCR. Low-level MMR protein expression was observed in five patients: One patient with primary cSCC < 2 mm thickness and low-level MLH1, three patients with primary cSCC > 6 mm (including one with low-level MSH2, as well as MSH6 expression, and two with low-level PMS2), and one patient with a cSCC metastasis showing low-level MSH2 as well as MSH6. Intergroup protein expression analysis revealed that MLH1 and MSH2 expression in actinic keratosis was significantly decreased when compared to Bowen's disease, cSCC < 2 mm, cSCC > 6 mm, and cSCC metastasis. In cases with low-level MMR, we performed MSI-H tests revealing three cases with MSI-H and one with low-level MSI-L. We found low-level MMR expression in a small subset of patients with invasive or metastatic cSCC. Hence, loss of MMR expression may be associated with tumour progression in a small subgroup of patients with non-melanoma skin cancer.


Assuntos
Carcinoma de Células Escamosas , Neoplasias Cutâneas , Carcinoma de Células Escamosas/genética , Reparo de Erro de Pareamento de DNA/genética , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Humanos , Instabilidade de Microssatélites , Endonuclease PMS2 de Reparo de Erro de Pareamento/genética , Endonuclease PMS2 de Reparo de Erro de Pareamento/metabolismo , Proteína 1 Homóloga a MutL/genética , Proteína 1 Homóloga a MutL/metabolismo , Proteína 2 Homóloga a MutS/genética , Proteína 2 Homóloga a MutS/metabolismo , Neoplasias Cutâneas/genética
19.
Pathologe ; 42(5): 509-523, 2021 Sep.
Artigo em Alemão | MEDLINE | ID: mdl-34415383

RESUMO

BACKGROUND: In Germany pancreas transplants are performed in only a few selected and specialized centres, usually combined with a kidney transplant. Knowlegde of the indications for and techniques of transplantation as well as of the histopathological assessment for rejection in pancreas and duodenal biopsies is not very widespread. AIM: To give an overview of the development and status quo in pancreas-kidney-transplantation in Germany summarizing the experience of the largest German pancreas transplant centre and to give a résumé of the results of histological diagnoses of biopsy specimens submitted between 06/2017 and 12/2020. Moreover, a detailed description and illustration of histological findings is included. MATERIAL AND METHODS: A thorough literature search for aspects of the history, technique and indication for pancreas transplantation was performed and discussed in the context of the local experience and technical particularities specific for the transplant centre in Bochum. The occurrence of complications was compared with international reports. Results of pancreas and duodenal biopsies submitted to Erlangen between 06/2017 and 12/2020 for histological evaluation, which were evaluated according to the Banff classification, were summarized. For a better understanding key histological findings of pancreas rejection and differential diagnoses were illustrated and discussed. RESULTS: A total of 93 pancreas transplant specimens and 3 duodenal biopsies were included. 34.4% of pancreas specimens did not contain representative material for a diagnosis. In the remaining 61 biopsies 24.6% showed no rejection, 62.3% were diagnosed with acute T-cell mediated rejection (TCMR) and 8.2% with signs suspicious of antibody-mediated rejection (ABMR). Acute acinary epithelial injury was seen in 59%, pancreatitis in 8.2% and allograft fibrosis was reported in as many as 54.1%. Calcineurin-inhibitor toxicity was discussed in only 4.9%. CONCLUSION: Pancreas-kidney-transplantation and standardized histological assessment of the transplanted pancreas or rarely duodenum with reporting according to the updated Banff classification of pancreas transplants or previous reports of duodenal rejection are important mainstays in the management of patients with diabetes.


Assuntos
Transplante de Rim , Transplante de Pâncreas , Biópsia , Rejeição de Enxerto , Humanos , Rim
20.
Ultrasonography ; 40(4): 546-554, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34399044

RESUMO

PURPOSE: The aim of this study was to retrospectively evaluate contrast-enhanced ultrasound (CEUS) findings in patients with peliosis hepatis (PH). METHODS: A retrospective analysis was conducted of CEUS features in 24 patients with histopathologically confirmed PH (11 men and 13 women; mean age, 32.4±7.1 years; range, 28 to 41 years). All lesions were histologically proven, either by core needle biopsy (n=10) or by hepatic surgery (n=14). RESULTS: The mean size was 36.8±12.4 mm (range, 10 to 80 mm). On B-mode ultrasonography (BMUS), all PH lesions were heterogeneously hypoechoic, with well-defined margins but irregular shapes. No mass effect was observed. During the arterial phase of CEUS, all lesions displayed mild heterogeneous hyperenhancement (83.3%, 20/24) or isoenhancement (16.7%, 4/24). Furthermore, 87.5% of the PH lesions showed mild washout after 1 minute in the portal venous phase (30-120 seconds) and mild washout in the late phase (>120 seconds). CONCLUSION: The lack of a mass effect on BMUS, mild heterogeneous arterial hyperenhancement, and washout in the very late portal venous phase (after 1 minute) on CEUS are characteristic of PH. Although it is a histological diagnosis, PH should be considered in the differential diagnosis when the clinical context does not favor a malignancy or infection.

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