Remission of Thymoma on Steroid Therapy in a Patient With Atypical Thymoma-Associated Multiorgan Autoimmunity: A Case Report and Literature Review.

In up to 34% of cases, thymoma, itself a rare neoplasm, is accompanied by autoimmune disorders, two of which are thymoma-associated multiorgan autoimmunity (TAMA) and paraneoplastic autoimmune multiorgan syndrome (PAMS). Unfortunately, differential diagnosis between these two entities can be challenging since no strict PAMS definition exists and PAMS can overlap with a subgroup of TAMA patients with skin lesions as leading presentation. We present a case of a 68-year-old woman with a diagnosis of thymoma accompanied by myasthenia gravis, hypothyroidism and GvHD-like mucocutaneous lesions that initially could account to both TAMA and PAMS diagnosis. However, following the exclusion of humoral autoimmunity against components of epithelial cells junction, TAMA was finally established. Interestingly, the introduction of corticosteroid therapy for TAMA symptom management resulted in unexpected partial remission of thymoma with no impact on mucocutaneous lesions. Our case study is an example of two extremely rare phenomena accompanying thymomas: unprecedented TAMA presentation with GvHD-like mucositis, which as we postulate should be placed in the spectrum of TAMA, and tumor remission on steroids.

The prognostic impact of neutrophil-to-lymphocyte ratio, lymphocyte-to-monocyte ratio, and platelet-to-lymphocyte ratio in patients with advanced colorectal cancer treated with first-line chemotherapy.

INTRODUCTION: Colorectal cancer is the second most frequently diagnosed malignancy and one of the leading causes of cancer-related death in Poland. Many reports of different types of cancer have indicated that blood count parameters may serve as a source of prognostic or predictive information. AIM: To assess the association between these parameters and clinical outcome in patients with advanced colorectal cancer. MATERIAL AND METHODS: We retrospectively analysed a database of 295 patients with advanced colorectal cancer treated with first-line palliative chemotherapy at our institution from January 2008 to December 2012. Blood-based parameters were measured before the first cycle of treatment. RESULTS: The median progression-free survival (PFS) was 6.7 months, and the median overall survival was 17.6 months. A high neutrophil-to-lymphocyte ratio (NLR) and a high platelet-to-lymphocyte ratio (PLR) were associated with a shorter survival (hazard ratio (HR): 1.88, p < 0.0001 for the NLR and HR: 1.39, p = 0.0054 for the PLR), but for the PLR, we observed only a not significant trend toward a worse PFS (HR = 1.25, p = 0.07 for the PLR and HR = 1.55, p = 0.0004 for the NLR). A high lymphocyte-to-monocyte ratio (LMR) was associated with a better prognosis (HR = 0.58, p ≤ 0.0001) and a longer PFS (HR = 0.73, p = 0.011). CONCLUSIONS: The blood-based parameters are readily available, reliable, and low-cost biomarkers, which can be easily incorporated into routine practice to predict the prognosis in patients with advanced colorectal cancer.

Nicotine-induced resistance of non-small cell lung cancer to treatment--possible mechanisms.

Cigarette smoking is the leading risk factor of lung cancer. Data from several clinical studies suggest that continuation of smoking during therapy of tobacco-related cancers is associated with lower response rates to chemotherapy and/or radiotherapy, and even with decreased survival. Although nicotine--an addictive component of tobacco--is not a carcinogen, it may influence cancer development and progression or effectiveness of anti-cancer therapy. Several in vitro and in vivo trials have evaluated the influence of nicotine on lung cancer cells. The best known mechanisms by which nicotine impacts cancer biology involve suppression of apoptosis induced by certain drugs or radiation, promotion of proliferation, angiogenesis, invasion and migration of cancer cells. This effect is mainly mediated by membranous nicotinic acetylcholine receptors whose stimulation leads to sustained activation of such intracellular pathways as PI3K/Akt/mTOR, RAS/RAF/MEK/ERK and JAK/STAT, induction of NF-κB activity, enhanced transcription of mitogenic promoters, inhibition of the mitochondrial death pathway or stimulation of pro-angiogenic factors. We herein summarize the mechanisms underlying nicotine's influence on biology of lung cancer cells and the effectiveness of anti-cancer therapy.

A retrospective evaluation of associations between chronic obstructive pulmonary disease, smoking, and efficacy of chemotherapy and selected laboratory parameters in patients with advanced non-small cell lung cancer.

AIM OF THE STUDY: To was to determine the impact of chronic obstructive pulmonary disease (COPD) and active smoking on the efficacy of chemotherapy and complete blood count (CBC) in patients with non-small cell lung cancer (NSCLC). MATERIAL AND METHODS: The retrospective evaluation included 50 patients with stage IIIB-IV NSCLC, who started cisplatin-based chemotherapy. Peripheral blood CBC values were collected for testing before chemotherapy and after the first and third cycles. RESULTS: COPD was diagnosed in 49% of patients, while 42% of those enrolled were current smokers. Current smoking (p = 0.92) and COPD (p = 0.91) status did not affect the response to treatment. The non-COPD population presented a significantly higher pretreatment absolute lymphocyte count (ALC) than the COPD population (2.31 vs. 1.81 × 109/l; p = 0.0374). Also, only the non-COPD group demonstrated an elevated absolute monocyte count (AMC) following the first and third cycles of chemotherapy (p = 0.004). In current smokers, pretreatment values for white blood cells (WBC), absolute neutrophil count (ANC), and platelets (PLT) were higher than in the ex-smoker population (WBC 9.94 vs. 8.7 (× 109/l); p = 0.01; ANC 6.47 vs. 5.61 (× 109/l); p = 0.037; PLT 316 vs. 266 (× 109/l); p = 0.049). Ex-smokers demonstrated AMC level elevation after the first cycle of chemotherapy and PLT level elevation after the third cycle, while current smokers also demonstrated an early decrease in LMR. CONCLUSIONS: COPD and smoking induce chronic systemic inflammation and oxidative stress, which influence the results of standard laboratory tests, but do not change the response rate of lung cancer on chemotherapy.

Synchronous primary ovarian and endometrial cancers: a series of cases and a review of literature.

Synchronous cancers account for 0.7-1.8% of all gynecologic cancers. Among them, synchronous ovarian and endometrial cancers are predominant (40-53%). Patients with synchronous cancers have better prognosis than those with single disseminated cancer. We present 10 patients with synchronous ovarian and endometrial cancers who were treated at the Chemotherapy Department of the Medical University of Lodz in 2009-2013. The most often reported symptom of the disease was abnormal vaginal bleeding (6 patients). The range of the patients' age was 48-62 and the median age was 56. Five patients had stage I of ovarian cancer, single patients had stage IIA, IIB and IIIB, 2 patients had stage IIIC. Three patients had I, 5 - II, and 2 - III stage of endometrial cancer. All patients had endometrioid type of endometrial cancer, 7 of them had also the same histological type of ovarian cancer. All patients had adjuvant chemotherapy because of ovarian cancer, none of them had adjuvant radiotherapy. One patient was lost to follow up. For other patients a median follow up was 13 months (range: 3-53 months). One patient experienced relapse, all patients are alive. Synchronous ovarian and endometrial cancers are usually diagnosed at an earlier stage, have lower histological grade and better prognosis than single cancers. The most common histological type of both endometrial and ovarian cancers is endometrioid carcinoma. The first symptoms reported by our patients and the course of the disease were concordant with data from the literature.

Tamoxifen-induced acute pancreatitis - a case report.

Tamoxifen is a selective estrogen receptor modulator used for the treatment of oestrogen/progesterone receptor positive breast cancer. It has antagonistic or agonistic activity depending on the tissue location. Generally it causes mild and reversible side effects, however more serious ones including cardiovascular and thromboembolic adverse events, uterine cancer or acute pancreatitis can also occur. Tamoxifen, like oestrogens, increases the plasma level of TG and liver secretion of VLDL. Moreover, it inhibits the key enzymes of triglyceride metabolism. In this report we present a case of a 55-year-old woman with a history of a poorly controlled hypertriglyceridaemia diagnosed with breast cancer. She was treated with surgery and adjuvant chemotherapy, radiotherapy and hormonotherapy with tamoxifen. About three months after hormonal treatment, her triglyceride level increased. Five months later she developed an acute necrotic pancreatitis that required hospitalization. Her serum samples on admission were highly lipemic. An abdominal ultrasound showed no evidence of gallstones or dilation of the bile ducts. There was no history of alcohol abuse or abdominal trauma. Tamoxifen was suspected as a trigger factor for pancreatitis. After the drug withdrawal and administration of the conservative management the patient's medical condition improved. Due to a postmenopausal status of the patient and no harmful effect on serum lipids, an adjuvant hormonotherapy with aromatase inhibitor was started.

[PARP inhibitors--theoretical basis and clinical application]. / Inhibitory PARP--podstawy teoretyczne i zastosowanie kliniczne.

Poly-ADP-ribose polymerases (PARP) are involved in a number of processes that are vital for every living cell. Once activated by the presence of DNA damage they trigger poly-ADP-ribosylation of various proteins which are crucial for DNA repair, preserving of genom integrity, regulation of transcription, proliferation and apoptosis. PARP1, which is the best known enzyme of PARP protein family, plays a role in single-strand breaks (SSB) repair. Decrease of its activity results in accumulation of single strand DNA breaks (SSB) which leads as a consequence to double-strand breaks (DSBs). This disorder is particularly harmful to cells with deficiency of BRCA1/2 protein which is involved in repair of DNA double-strand breaks. This phenomenon is an example of "synthetic lethality" concept and contributes to research on application of PARP inhibitors in treatment of cancers associated with BRCA1/2 protein defect (breast or ovarian cancer). Noticed synergism between PARP inhibitors and genotoxic chemotherapy or radiotherapy determined another direction of research on application of these medicaments. After promising results of phase I and II trials with most commonly investigated PARP inhibitors--iniparib and olaparib--which recruited patients with triple negative breast cancer and ovarian cancer, further studies started. This paper presents theoretical basis of PARP inhibitors action as well as critical review of most important clinical trials of these medicaments.