Igor Richter

Gastric and Colorectal Metastases of Lobular Breast Carcinoma: A Case Report.

BACKGROUND Occurrence of gastric metastasis as the first symptom of breast carcinoma with a long period of latency before presentation of the primary breast carcinoma is rare. CASE REPORT A patient with gastric metastasis as the first symptom of lobular breast carcinoma, treated by neoadjuvant preoperative chemoradiotherapy and total gastrectomy, with complete local control. Fourteen months after presentation of the gastric metastasis a primary lobular breast carcinoma was discovered, treated by radiotherapy, chemotherapy and hormonal treatment with complete local response. Twenty-three months after diagnosis of breast cancer multiple colorectal metastases from the breast cancer occurred, which were treated by chemotherapy and hormonal treatment. Eighty-six months after diagnosis of gastric metastasis the patient died due to progression of cancer. CONCLUSIONS Metastases to gastrointestinal or gynaecological tracts are more likely in invasive lobular carcinoma than invasive ductal cancer. The pathologist should determine whether or not they check estrogen and progesterone receptor status not simply by signet ring cell morphology but also by consideration of clinic-pathological correlation of the patient, such as the presence of a past history of breast cancer, or the colorectal localization of poorly differentiated carcinoma, which may occur less frequently than in the stomach.

Treatment of Metastatic Renal Cell Carcinoma

INTRODUCTION Renal cell cancer accounts for approximately 2-3% of all cases of malignancy. The incidence of kidney cancer in the Czech Republic is the highest in the world. Approximately 70% of renal cell carcinomas are clear-cell renal cancer. Various treatment options for metastatic renal cell cancer (mRCC) have been developed. Treatment regimens comprise antiangiogenic drugs in combination with vascular endothelial growth factor receptor inhibitors, mTOR inhibitors, and immunotherapy. AIM This review provides an overview of the current treatment options for mRCC. Patients with a good performance status and a low systemic disease burden are candidates for cytoreductive nephrectomy. Ablative methods, such as stereotactic radiotherapy, can be used in patients with oligometastatic disease. Sunitinib and pazopanib are preferred first-line treatments for mRCC and provide similar outcomes. Second-line and higher line treatments markedly changed with the development of new drugs, such as cabozantinib and the immunotherapy nivolumab. The optimal treatment sequence for mRCC is discussed. Ongoing studies are evaluating combined treatments and searching for potential biomarkers. However, the tumor heterogeneity of renal cell cancer complicates the use of biomarkers. CONCLUSION The results of clinical trials have markedly changed the treatment guidelines for mRCC. New strategies include combinatorial approaches, which mainly incorporate immunotherapy.Key words: renal cancer - targeted therapy - immunotherapy - metastases - biomarkers The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study. The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers.Submitted: 19. 12. 2017Accepted: 7. 1. 2018.

Options of Chemotherapy in the Treatment of Prostate Cancer

BACKGROUND Prostate cancer is one of the most common malignancies in men. Chemotherapy has an important role in the management of prostate cancer, especially for the treatment of castrate resistant prostate cancer (mCRPC). According to recently published studies, chemotherapy can also be used to treat advanced hormone sensitive disease. AIM The aim of this report is to review the currently available options for chemotherapy of prostate cancer. RESULTS Docetaxel is a chemotherapeutic agent used for standard treatment of mCRPC as 1st line therapy. In TAX 327 and SWOG 9916 studies reported in 2004, docetaxel, the first cytostatic agent indicated for this disease, prolonged overall survival. As a 2nd line mCRPC treatment, kabazitaxel resulted in longer overall survival than mitoxantrone, according to the results of the TROPIC study. Targeted hormone treatment, radium-223 irradiation, and immunotherapy are other treatment options for patients with mCRPC. Currently, the main focus is to develop an optimal sequence of treatments. Standard androgen deprivation therapy (ADT) is the standard option for patients with advanced hormone sensitive prostate cancer. According to recently published studies (CHAARTED, STAMPEDE), docetaxel with ADT increases overall survival in this group of patients. In the Czech Republic, this option is still off-label. Chemotherapy is not indicated in patients with early prostate cancer after radical prostatectomy or radiotherapy.Key words: prostate cancer - metastasis - chemotherapy - docetaxel - cabazitaxelThe authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study.The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers.Submitted: 9. 5. 2016Accepted: 6. 6. 2016.

The prognostic significance of tumor epidermal growth factor receptor (EGFR) expression change after neoadjuvant chemoradiation in patients with rectal adenocarcinoma.

Aim of the study The aim of this retrospective study was to determine the prognostic impact of epidermal growth factor receptor (EGFR) expression changes during neoadjuvant chemoradiotherapy in patients with locally advanced rectal cancer. Material and methods Fifty patients with locally advanced rectal cancer were evaluated. All the patients were administered the total dose of 44 Gy. Capecitabine has been concomitantly administered in the dose 825 mg/m2 in two daily oral administrations. Surgery was indicated 4–8 weeks from the chemoradiotherapy completion. Epidermal growth factor receptor expression in the pretreatment biopsies and in the resected specimens was assessed with immunohistochemistry. Results All of 50 patients received radiotherapy without interruption up to the total planned dose. In 30 patients sphincter-saving surgery was performed, 20 patients underwent amputation of the rectum. Downstaging was described in 30 patients. Four patients have had complete pathologic remission. Twenty-six patients have had partial remission, the disease was stable in 15 patients. Progression was reported in 5 patients. The median disease-free survival was 64.9 months, median overall survival was 76.4 months. Increased EGFR expression was found in 12 patients (26.1%). A statistically significantly shorter overall survival (p < 0.0001) and disease-free survival (p < 0.0001) was found in patients with increased expression of EGFR compared with patients where no increase in the expression of EGFR during neoadjuvant chemoradiotherapy was observed. Conclusions The overexpression of EGFR during neoadjuvant chemoradiotherapy for locally advanced rectal adenokarcinoma associated with significant shorter overall survival and disease free survival.

The changes of tumour vascular endothelial growth factor expression after neoadjuvant chemoradiation in patients with rectal adenocarcinoma

Aim of the study The aim was to examine the effects of neoadjuvant chemoradiotherapy on VEGF expression in patients with locally advanced rectal cancer. Materials and methods A total of 53 patients with locally advanced rectal cancer were retrospectively studied. Neoadjuvant treatment comprised external beam radiation (50.4 Gy/28 fractions) with continuous infusion of 5-fluorouracil. Four to 6 weeks after the chemoradiotherapy, the patients underwent surgical resection. Immunohistochemistry was performed to assess VEGF expression in the pretreatment biopsies and in resected specimens. Results Resection with microscopic residual tumour (R1) was performed in two patients while in the remaining 51 patients radical resection with microscopically negative margins (R0) was possible. Downstaging after preoperative chemoradiotherapy was observed in 34 patients (64%). After chemoradiotherapy 24 patients (45%) had decreased VEGF expression, in 20 patients (38%) there was no change, and in two patients it was not possible to assess the dynamics of VEGF expression due to pathologic complete response after chemoradiotherapy. The five-year overall survival (OS) rate was 56% (95% CI: 43–70%). Although the median OS was 2.5 times shorter in patients who experienced decreased VEGF expression during therapy, this difference did not reach statistical significance. VEGF expression was not significant in Cox regression analysis or log-rank test. VEGF expression decreased after neoadjuvant chemoradiotherapy in most patients with rectal adenocarcinoma examined. This decrease was associated with a trend of inferior prognosis. Conclusions VEGF expression decreased after neoadjuvant chemoradiotherapy in most patients examined. This decrease was associated with a trend of inferior prognosis.

Docetaxel–Cabazitaxel–Enzalutamide Versus Docetaxel–Enzalutamide in Patients with Metastatic Castration-resistant Prostate Cancer

AIM The aim of this retrospective study was to compare the efficacy of the sequence docetaxel-cabazitaxel-enzalutamide vs. docetaxel-enzalutamide in patients with metastatic castration-resistant prostate cancer. PATIENTS AND METHODS Of the cohort of 35 patients, 11 were treated with the sequence docetaxel-cabazitaxel-enzalutamide and 24 were treated with the sequence docetaxel-enzalutamide. The doses were as follows: docetaxel, 75 mg/m2; cabazitaxel, 25 mg/m2; and enzalutamide, 160 mg/day. Overall survival (OS) was defined as the interval between the initial dose of docetaxel and death or the date of the last control for survivors (censored). OS was assessed using the Kaplan-Meier method, and the two arms were compared using the log-rank test. The significance level for all statistical tests was set at α = 0.05. RESULTS The median OS of patients treated with the sequence docetaxel-cabazitaxel-enzalutamide was 28.8 months, vs. 24.4 months in patients treated with the sequence docetaxel-enzalutamide. No statistically significance differences in OS were found between the two arms (HR 0.678, 95% CI 0.264-1.744; p = 0.418). Grade 3-4 toxicity was observed for each drug, as follows: docetaxel: fatigue and peripheral neuropathy in six patients, nausea in three patients, and diarrhea and neutropenia in one patient; cabazitaxel: anemia in two patients and neutropenia in one patient; and enzalutamide: anemia in six patients, thrombocytopenia in two patients, and cerebral hemorrhage in one patient. CONCLUSION No statistically significant differences in OS were found between the sequences docetaxel-cabazitaxel-enzalutamide and docetaxel-enzalutamide.Key words: prostate cancer - metastasis - chemotherapy - targeted hormonal treatment The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study. The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers.Submitted: 13. 2. 2017Accepted: 20. 3. 2017.

The combination of neoadjuvant chemoradiotherapy and epidermal growth factor receptor inhibitors in the treatment of rectal adenocarcinoma

Rectal adenocarcinoma, in contrast to colorectal carcinoma, is typical of its high local reccurence rate. Radiotherapy is proved to reduce the incidence of recurrences. Neoadjuvant chemoradiotherapy demonstrated better treatment results than adjuvant chemoradiotherapy. Standard cytotoxic agents involved in combination therapy are 5- flurouracil or capecitabin. Epidermal growth factor receptor (EGFR) is supposed to play an important role in cell- cycle regulation, proliferation, differentiation, and surviving of normal epithelial tissues. EGFR overexpression in patients with rectal adenocarcinoma is associated with radioresistance of malignant tissues, lower rates of patological complete response after neoadjuvant chemoradiation and generally poor survival. There are many clinical studies describing combination of neoadjuvant chemoradiotherapy with EGFR inhibitors, however, this regimen has not gained an acceptance as a standard of treatmentment.

Primary cilium - antenna-like structure on the surface of most mammalian cell types

The primary cilium is a sensory solitary non-motile microtubule-based organelle protruding in the quiescent phase of the cell cycle from the surface of the majority of human cells, including embryonic cells, stem cells and stromal cells of malignant tumors. The presence of a primary cilium on the surface of a cell is transient, limited to the quiescent G1(G0) phase and the beginning of the S phase of the cell cycle. The primary cilium is formed from the mother centriole. Primary cilia are key coordinators of signaling pathways during development and tissue homeostasis and, when deffective, they are a major cause of human diseases and developmental disorders, now commonly referred to as ciliopathies. Most cancer cells do not possess a primary cilium. The loss of the primary cilium is a regular feature of neoplastic transformation in the majority of solid tumors. The primary cilium could serve as a tumor suppressor organelle. The aim of this paper was to provide a review of the current knowledge of the primary cilium.