Chirurgische Therapie im Stadium I und II des nichtkleinzelligen Lungenkarzinoms

Background

Despite modern diagnostics and multimodal treatment strategies, overall survival of lung cancer could not be significantly improved in recent decades. The majority of patients with non-small cell lung cancer (NSCLC) have distant metastases at the time of diagnosis (57%) and only approximately 40% of patients are in a potentially curable tumor stage.

Material and methods

A systematic literature search concerning original research and review articles on surgery of NSCLC in stages I and II was carried out in the PubMed database.

Results

For patients in an early tumor stage, stages I and II tumors according to the 8th edition of the Union for International Cancer Control (UICC) tumor stage classification, surgical removal of the tumor remains the therapeutic gold standard. By complete anatomical resection (lobectomy, bilobectomy or pneumonectomy) combined with a systematic mediastinal and hilar lymphadenectomy, 5?year survival rates of more than 80% in early stage IA and 48% in stage II can be achieved. In addition to open surgical resection, video-assisted, minimally invasive thoracoscopic (VATS) resection was successfully implemented worldwide for the treatment of NSCLC patients in stages I and II. For patients with stage II NSCLC, adjuvant chemotherapy was shown to improve the overall survival.

Discussion

Whether targeted therapies or immunotherapy in a neoadjuvant or adjuvant treatment modality further improve the survival of NSCLC patients in the multimodal treatment of early stage NSCLC, is currently under investigation in randomized studies.

     

Zervixkarzinom und seine Vorstufen

Background

The nomenclature of squamous and glandular precursor lesions has been reformed in the World Health Organization (WHO) classification as well as in national and international guidelines in recent years.

Methods

This study was based on a PubMed search and a review of current national and international guidelines pertaining to the subject.

Results

With regards to cervical intraepithelial neoplasia associated with human papillomavirus (HPV), an accurate distinction between low grade and high grade squamous intraepithelial lesions (LSIL and HSIL, respectively) and a thorough evaluation of glandular precursor lesions are emphasized. Morphological changes associated with the productive phase of HPV infection are referred to as LSIL and changes associated with deregulation of HPV expression and of the cell cycle as HSIL; however, for the clinical management of squamous cell precursor lesions, the 3?tiered classification of cervical intraepithelial neoplasia (CIN) is still indispensable. In the differential diagnosis of HPV-associated precursors and metaplastic squamous cell and glandular lesions in particular, the relevance of p16 immunohistochemistry or combined p16/Ki-67 determination is emphasized. The staging of cervical cancer has been complemented by subdividing stage IIA into IIA1 and IIA2 and the importance of a standardized determination of morphological prognostic factors is underlined. Particular attention must be paid to differentiate special types of squamous cell carcinoma and rare non-HPV associated adenocarcinomas.

Conclusion

The recently updated recommendations and guidelines on the diagnosis and classification of cervical cancer have taken our improved understanding of the biology and natural history of the disease into account.

     

Bewältigungsstrategien in der Onkologie

Background

Coping with cancer is a great challenge for patients and their relatives. The initial shock of the diagnosis is followed by different coping strategies and phases of adaptation and processing of the situation.

Methods

This article is based on a selective literature search in PubMed on the topic of coping with disease and cancer.

Results and discussion

Psychosocial resources and factors of resilience can heIp patients to find positive perspectives apart from all the negative aspects associated with cancer. Coping with denial requires a sensitive handling by professionals bearing in mind the protective character of this coping strategy for the mental state of patients. Confrontation with reality is only a realistic option if denial results in damaging effects. Aggression and depression are antagonists in disease processing and coping strategies and are often in danger of becoming unbalanced. It must be taken into consideration that a reactive depressive mood might be an adequate state, whereas a depressive episode should be differentiated as a mental comorbidity that needs to be treated.

     

Saffron Can Prevent Chemically Induced Murine Skin Carcinogensis In Swiss Albino Mice

One of the most promising strategies for cancer prevention today is chemoprevention using readily available ‍natural substances from vegetables, fruits, herbs and spices . Among the spices, saffron (Crocus sativus, L) a member ‍of the large family Iridaceae, has drawn attention because apart from its use as a flavouring agent, pharmacological ‍studies have demonstrated many health promoting properties including radical scavenging, anti- mutagenic and ‍immuno-modulating effects. In the present study the effects of an aqueous infusion of saffron on two stage skin ‍papillogenesis / carcinogenesis in mice initiated by 7-12 dimethyl benz[a] anthracin (DMBA) and promoted with ‍croton oil were investigated. Significant reduction in papilloma formation was found with saffron application in the ‍pre-initation and post-initation periods, and particular when the agent was given both pre- and post-initation. The ‍inhibition appeared to be at least partly due on modulatory effects of saffron on some phase II detoxifying enzymes ‍like glutathione-S-transferase (GST) and glutahinoe peroxidase (GPx), as well as catalase (CAT) and superoxide ‍dismutase (SOD). ‍     

A Retrospective Study of Double-hit Lymphomas in Elderly Patients (Aged > 70 Years): Overall Outcomes

Background

Double-hit lymphomas (DHLs) are high-grade diffuse large B-cell lymphomas with concurrent translocations involving myc and bcl-2 and/or bcl-6. A patient with DHL often has advanced disease at presentation and typically responds poorly to standard therapy with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone). More intensive treatment regimens have been studied; however, few data are available on the outcomes in elderly patients (aged > 70 years) treated with these therapies. We retrospectively studied the efficacy and tolerability of chemotherapy regimens in elderly patients within the Advocate Healthcare System.

Vitamin B12 and Folate Status in Head and Neck Cancer

Deficiency of vitamin B12 and folate is associated with causation of certain precancerous conditions and cancer.The present study was carried out on 56 controls, 167 patients with oral precancerous conditions (OPC) and 214head and neck cancer patients, to evaluate the plasma vitamin B12 and folate levels to determine their associationwith tobacco habits and vegetarianism and several sociodemographic factors. The subjects were interviewed using ahealth habit and diet questionnaire at the time of blood collection. Simultaneous estimations of plasma vitamin B12and folate were done by Dual Count Radioassay. It was found that the habit of tobacco consumption, lower educationand low income were among the risk factors. A decrease in the plasma vitamin B12 and folate levels with respect totobacco habits, disease progression, and vegetarian diet was also observed. The individuals in the ower quartile forvitamin B12 and folate were at a higher risk of developing OPC, as compared to those in higher quartiles. Similarly,the patients with OPC in lower quartiles were found to be at a higher risk of developing cancer than their counterparts.There was a significant positive correlation between vitamin B12 and folate levels in the subjects consuming tobacco,and more so in patients with OPC (r=0.4330, p=0.000). Folate levels were significantly lower in patients with advancedas compared with early disease (ANOVA p=0.006 and Spearman’s Rho = -0.211 and p=0.01). The results suggest,potential significance of plasma vitamin B12 and folate levels in head and neck malignancies which needs to beconfirmed by further studies on a large population.     

Humane Papillomaviren und Zervixkarzinom

Background

Cervical cancer is the fourth most commonly occurring malignancy in women worldwide. Extrapolations by the Robert Koch Institute on the basis of cancer registry data in Germany showed that approximately 4600 women were diagnosed with cervical cancer in 2012.

Results

The cause of cervical cancer is a long-lasting infection with certain types of human papillomavirus (HPV) and without these viruses almost no cases of cervical cancer occur. A differentiation is made between types of virus that cause mainly warts (so-called low-risk types) and those that can trigger cancer (high-risk types). The first group includes HPV 6 and 11 and the second group includes types HPV 16 and 18, which are responsible for approximately 70?% of all cervical cancer cases. Since 2006 two vaccines have been available against the two types with the highest risk (HPV 16 and 18) and since 2015 there is a vaccine on the market that protects against five additional high-risk types (HPV 31, 33, 45, 52 and 58). This new nonavalent vaccine can prevent roughly 90?% of cervical cancers.

Conclusion

Regular participation in cervical cancer screening programs is still recommended.

     

Clinical outcomes linked to expression of gene subsets for protein hormones and their cognate receptors from LCM-procured breast carcinoma cells

Purpose

Certain peptide hormones and/or their cognate receptors influencing normal cellular pathways also have been detected in breast cancers. The hypothesis is that gene subsets of these regulatory molecules predict risk of breast carcinoma recurrence in patients with primary disease.

Methods

Gene expression levels of 61 hormones and 81 receptors were determined by microarray with LCM-procured carcinoma cells of 247 de-identified biopsies. Univariable and multivariable Cox regressions were determined using expression levels of each hormone/receptor gene, individually or as a pair.

Results

Molecular signatures for ER+/PR+, ER?/PR?, and ER? carcinoma cells deciphered by LASSO were externally validated at HRs (CI) of 2.8 (1.84–4.4), 1.53 (1.01–2.3), and 1.72 (1.15–2.56), respectively. Using LCM-procured breast carcinoma cells, a 16-gene molecular signature was derived for ER+/PR+ biopsies, whereas a 10-gene signature was deciphered for ER?/PR? cancers. Four genes, POMC, CALCR, AVPR1A, and GH1, of this 10-gene signature were identified in a 6-gene molecular signature for ER? specimens.

Conclusions

Applying these signatures, Kaplan–Meier plots definitively identified a cohort of patients with either ER?/PR? or ER? carcinomas that exhibited low risk of recurrence. In contrast, the ER+/PR+ signature identified a cohort of patients with high risk of breast cancer recurrence. Each of the three molecular signatures predicted clinical outcomes of breast cancer patients with greater accuracy than observed with either single-gene analysis or by ER/PR protein content alone. Collectively, our results suggest that gene expression profiles of breast carcinomas with suspected poor prognosis (ER?/PR?) have identified a subset of patients with decreased risk of recurrence.

     

Nichtseminom im klinischen Stadium I

Context

In patients with clinical stage I nonseminomatous germ cell tumors (NSGCT CS I) the most important prognostic factor for tumor relapse is vascular or lymphatic tumor invasion.

Material and methods

Research of literature and analysis of clinical trials.

Results

In patients with clinical stage I nonseminomatous germ cell tumors (NSGCT CS I) the most important prognostic factor for tumor relapse is vascular or lymphatic tumor invasion. There are three different adjuvant treatment options: cisplatin-based chemotherapy, nerve-sparing retroperitoneal lymphadenectomy (NS-RPLND) or surveillance. Patients with NSGCT CS I without vascular invasion should be managed by a surveillance strategy. Patients with vascular invasion should be recommended to undergo adjuvant chemotherapy with two cycles of bleomycin, etoposide and cisplatin (BEP) or a surveillance strategy. Data concerning a reduction from two cycles to one cycle of BEP for high-risk patients are emerging and indicate that the risk of recurrence is also correspondingly reduced and the dose-dependent long-term effects of chemotherapy, such as secondary malignancies or cardiotoxicity, could also possibly be reduced. Patients should be informed about this option. The NS-RPLND approach remains a very rare treatment option for those not willing or unable to undergo surveillance or adjuvant chemotherapy. If surgery is chosen it should be performed in dedicated referral centers in order to avoid excess morbidity.     

Seminom im klinischen Stadium I

Context

Stage I seminoma is the most commonly diagnosed testicular cancer and has an excellent prognosis. Independent of whether adjuvant treatment or active surveillance strategy is applied up to 100?% of patients can be cured.

Material and methods

Research of literature and analysis of clinical trials.

Results

The recurrence rate for stage I seminoma is approximately 15?%. A retrospective analysis identified invasion of the rete testis and a tumor size of >?4 cm as prognostic risk factors; however, not all recent studies could confirm these findings. Relapse risk can be reduced to 4–5?% when adjuvant treatment with either single dose carboplatin area under the curve of 7 (AUC 7) or radiotherapy (para-aortic field with 20 Gy) is applied. However, this leads to overtreatment in 85?% of cases and there is concern about long-term toxicity.

Conclusions

Active surveillance therefore represents the preferred treatment option for the majority of patients with stage I seminoma according to most international guidelines. An optimal follow-up schedule based on published recommendations should be applied to avoid unnecessary exposure to ionizing radiation and to ensure patient compliance.     

An integrated in vitro and in vivo high-throughput screen identifies treatment leads for ependymoma

Using a mouse model of ependymoma-a chemoresistant brain tumor-we combined multicell high-throughput screening (HTS), kinome-wide binding assays, and in?vivo efficacy studies, to identify potential treatments with predicted toxicity against neural stem cells (NSC). We identified kinases within the insulin signaling pathway and centrosome cycle as regulators of ependymoma cell proliferation, and their corresponding inhibitors as potential therapies. FDA approved drugs not currently used to treat ependymoma were also identified that posses selective toxicity against ependymoma cells relative to normal NSCs both in?vitro and in?vivo, e.g., 5-fluorouracil. Our comprehensive approach advances understanding of the biology and treatment of ependymoma including the discovery of several treatment leads for immediate clinical translation.     

A Decade of Never-smokers Among Lung Cancer Patients—Increasing Trend and Improved Survival

Background

It is not known whether clinicopathologic characteristics, treatment, and survival of never-smokers among lung cancer incident cases have changed over time. We assessed the trend and overall survival (OS) of these patients within our institution during a 10-year period.