Comparison of different lymph node staging systems for predicting prognosis in patients with colon cancer who have undergone surgical resection.

At present, the most widely used lymph node (LN) staging system in colon cancer is number of metastatic LNs in pathological assessment (pN) from the 8th edition of the TNM American Joint Committee on Cancer/Union for International Cancer Control staging system, which considers the number of metastatic LNs, omitting the total number of dissected LNs. The aim of the present study was to compare the prognostic performance of pN with alternative LN staging systems, including LN ratio (LNR) and log odds of positive LNs (LODDS). The clinical and histopathological data of 298 patients with colon cancer who underwent elective surgical resection in a single surgical centre were analysed. LNR and LODDS cut-off values according to two previous studies were selected to separate patients into different subgroups. Univariate and multivariate analyses were performed to distinguish prognostic factors. The three-step multivariate analysis showed that LNR was a superior prognostic indicator compared with pN and LODDS. Additionally, the Akaike Information Criterion, a measure of the relative quality of statistical models, confirmed that LNR displayed the best prognostic performance. Similarly, in a subpopulation of patients with number of dissected LNs (NDLN) ≥12, LNR was the most accurate LN staging system in relation to prognosis. In a subpopulation with NDLN <12, there was no significant difference in LN classification prognosis of 5-year overall survival; however, LNR and LODDS were more independent of NDLN than pN. Among the three LN classifications, LNR is the most accurate LN staging system for predicting prognosis for patients with colon cancer who have undergone surgical resection, particularly those with metastatic LNs subjected to adequate lymphadenectomy.

The effect of l-arginine supplementation and surgical trauma on the frequency of myeloid-derived suppressor cells and T lymphocytes in tumour and blood of colorectal cancer patients.

PURPOSE: l-arginine (L-arg) deficiency causes immunosuppression, but it is unknown if L-arg supplementation in colorectal cancer (CRC) patients restores immune system activity. Our objective was to investigate the effect of L-arg supplementation on the frequency of monocytic (M) and polymorphonuclear (PNM) myeloid-derived suppressor cells (M-MDSCs and PMN-MDSCs, respectively). METHODS: We enrolled 65 CRC patients (34 males, 31 females) aged 69 â€‹± â€‹10 years into a prospective, randomised, double-blind study. Twenty-eight patients received L-arg and 37 received placebo for 9 days at a dose of 10 â€‹g/day. The frequency changes in MDSC, CD4+ cells and the concentration of C-reactive protein (CRP) were assessed before supplementation with L-arg (test 1), after 9 days of supplementation (test 2), and after surgery on day 11 (test 3). RESULTS: The frequency of M-MDSC in the tumours of patients receiving L-arg supplementation was higher than in placebo-treated patients, as was the frequency of PMN-MDSC and M-MDSC in the mucosa. CRP concentration in the serum of placebo-treated patients in test 2 was higher than in test 1, and the concentration in the serum of patients with L-arg supplementation in test 2 was lower than in test 1. Moreover, the expression pattern of the argininosuccinate synthase 1 (ASS1) suggests that CRC is not auxotrophic for L-arg. CONCLUSIONS: The results of this study do not support the hypothesis that L-arg supplementation in CRC patients can reduce immunosuppression by decreasing the frequency of suppressor cells and increasing the frequency of effector CD4+ T cells.

Level of inferior mesenteric artery ligation does not affect rectal cancer treatment outcomes despite better cancer-specific survival after low ligation-randomized trial results.

AIM: In rectal cancer surgery, the problem about which of the mesenteric artery ligation variants (high or low) is more beneficial to the patient remains unsolved. Recent meta-analyses suggest that the risk of surgical complications is similar for both ligation variants. The main objective was to compare the survival time in both groups with a minimum 48 months' follow-up. Secondary objectives were comparison of the number of harvested lymph nodes, the complication rate and other selected data related to the surgery. METHOD: This was a randomized, single-centre, unblinded clinical trial of adult patients (n = 130) with cT1-3M0/ycT0-3M0 rectal and rectosigmoid junction adenocarcinoma undergoing radical open surgery. The intervention level was inferior mesenteric artery ligation. RESULTS: The mean and median survival in the whole group was 45 months, while in the survivor group it was 83 and 82 months. The survival for 1-5 years, overall survival and disease-free survival were similar in both groups. The cancer-specific survival time was longer in the low inferior mesenteric artery ligation group (P = 0.005 for all and P = 0.02 for pTNM Stage III patients) There were no differences in the incidence of anastomotic leakage and overall morbidity. The median number of lymph nodes located at the root of the inferior mesenteric artery was 1; the mean was 1.7. They were not metastatic in any case. The median total number of harvested nodes was similar in both groups. CONCLUSIONS: In radically treated adenocarcinoma of the rectum and the rectosigmoid junction, the level of inferior mesenteric artery ligation below the left colic artery branch provides similar treatment results to inferior mesenteric artery ligation just below its branching from the aorta in relation to overall and disease-free survival, and the risk of complications. Low inferior mesenteric artery ligation results in better cancer-specific survival. The risk of metastases at the mesenteric nodes is negligible.

Impact of chromosome 17 centromere copy number increase on patient survival and human epidermal growth factor receptor 2 expression in gastric adenocarcinoma.

The accurate evaluation of human epidermal growth factor receptor 2 (HER2) status is essential for the appropriate use of targeted therapies. An increased number of chromosome 17 centromere enumeration probe (CEP17) signals may underrate fluorescence in situ hybridization (FISH) outcomes, resulting in false-negative or a false-equivocal HER2 status assessment. The aim of the present study was to assess the frequency of CEP17 copy number increase (CNI), its effects on HER2 protein expression (and the subsequent effects on tumor cells), and the survival outcomes of patients with gastric cancer. Archival primary tumor samples from 244 patients that underwent gastric resection for adenocarcinoma were retrieved for both HER2 protein expression analysis (using immunochemistry) and HER2 gene amplification (using FISH). The associations between HER2 status, CEP17 CNI and multiple clinicopathological parameters (including survival outcome), were assessed. The relationship between CEP17 CNI and HER2 protein upregulation was also investigated. CEP17 CNI was detected in 17.2% of cases, and a strong association between CEP17 CNI and HER2 upregulation was revealed. The impact of CEP17 CNI on survival did not reach statistical significance. Consequently, CEP17 CNI was discovered to be strongly associated with HER2 upregulation in tumor cells, which may characterize a critical issue in HER2 testing. Therefore, the eligibility for HER2-targeted agents in CEP17 CNI-positive patients warrants further recognition.

Extremely High Mortality Rate after a Successful Gastrectomy for Cancer in Older Adults.

PURPOSE: Poor physiological reserve for withstanding major cancer surgery in older adults is an important concern in the selection of patients for oncologic gastrectomy. The present study aimed to analyze mortality patterns among patients who underwent gastrectomy for cancer according to age groups. The primary outcomes of this study were early- and middle-term results: 30-day and 3-, 6-, 12-, and 36-month mortality rates. MATERIALS AND METHODS: A retrospective review of 288 patients who underwent surgical resection for gastric cancer in two centers was carried out. Patients were stratified into four groups according to age: 29-50 years (group I, n=27), 51-65 years (group II, n=117), 66-75 years (group III, n=81), and 76-92 years (group IV, n=58). Statistical calculations focused on the differences in the survival rates between groups I and II as well as between groups II and IV. RESULTS: The middle-aged patients (group II) had significantly better 3-year survival than either the youngest (group I) or the oldest patients (group IV). The 6-month mortality rates were 16.9% in group III and 29.3% in group IV. Two-thirds of the patients from groups III and IV who died between 2 and 6 months after surgery had an uneventful postoperative course. CONCLUSIONS: Age is an important prognostic factor of middle-term survival after gastrectomy for cancer. Geriatric assessment and better patient selection for major surgery for cancer are required to improve the outcome of gastrectomy for cancer in patients aged over 75 years.

Metabolic pathways of L-arginine and therapeutic consequences in tumors.

Difference in the metabolism of normal and cancer cells inspires to search for new, more specific and less toxic therapies than those currently used. The development of tumors is conditioned by genetic changes in cancer-transformed cells, immunological tolerance and immunosuppression. At the initial stages of carcinogenesis, the immune system shows anti-tumor activity, however later, cancer disrupts the function of Th1/Th17/Th2 lymphocytes by regulatory T (Treg) cells, tumor-associated macrophages (TAMs), and myeloid-derived suppressor cells (MDSCs) and finally causes immunosuppression. Recently, much attention has been devoted to the influence of l-arginine metabolism disorders on both carcinogenesis and the immune system. l-Arginine is essential for the maturation of the T cell receptor zeta (TCRζ), and its absence deprives T-cells of the ability to interact with tumor antigens. MDSCs deplete l-arginine due to a high expression of arginase 1 (ARG1) and their number increases 4-10 times depending on the type of the cancer. L-Arginine has been shown to be essential for the survival and progression of arginine auxotrophic tumors. However, the progression of arginine non-auxotrophic tumors is independent of exogenous l-arginine, because these tumors have arginine-succinate synthetase (ASS1) activity and are available to produce l-arginine from citrulline. Clinical studies have confirmed the high efficacy of arginine auxotrophic tumors therapy based on the elimination of l-arginine. However, l-arginine supplementation may improve the results of treatment of patients with arginine non-auxotrophic cancer. This review is an attempt to explain the seemingly contradictory results of oncological therapies based on the deprivation or supplementation of l-arginine.

The relationship between HER2 overexpression and angiogenesis in gastric cancer.

In gastric cancer, HER2 protein overexpression is considered to be conducive to the higher proliferation activity of the tumor cells. Tumor formation is associated with angiogenesis in order to secure an abundant supply of oxygen and glucose to cancer cells. The aim of the study was to assess if HER2 overexpression is related to higher microvessel density (MVD) in the tumor stroma.The archival samples of primary tumor from 144 consecutive patients that underwent gastric resection for cancer between August 1, 2006 and December 31, 2013 in the Department of Oncological Surgery of Medical University of Gdansk were analyzed. CD34 was used as a marker of MVD in the tumor stroma. Both CD34 and HER2 protein expressions were tested by immunohistochemistry.The assays were unsuccessful to estimate HER2 in 10 cases and CD34 in 14 cases due to technical reasons. The results were obtained for 128 patients. HER2 0 and HER2 1+ were considered negative, while HER2+ and HER2 3+ were recognized as positive. Mean MVD (mean number of vessels in the visual field) was 32.4 (median 29.5). Microvessel density was insignificantly higher in HER2 positive tumors. The slight difference was also seen between IHC 2+ and 3+ groups. The differences did not reach the level of statistical significance.Statistical analysis performed in our study did not reveal the significant relationship between HER2 overexpression on the tumor cells and MVD in the tumor stroma.

Determination of tocopherols and tocotrienols in human breast adipose tissue with the use of high performance liquid chromatography-fluorescence detection.

Tocopherols and tocotrienols have been extensively studied owing to their anticancer potential, especially against breast cancer. Therefore, the aim of this study was to quantitatively determine tocochromanols in human breast adipose tissue with the use of HPLC-FLD. The sample preparation procedure included homogenization and solvent extraction with isopropanol-ethanol-0.1% formic acid mixture prior to solid-phase extraction. After implementation of central composite design, satisfactory separation of all eight target compounds was achieved within 10.5 min. Chromatographic runs were carried out with the use of a naphthylethyl chromatographic column with methanol-water mixture (89:11, v/v) as the mobile phase. Fluorescence detection of tocochromanols was performed with excitation and emission wavelengths 298 and 330 nm, respectively. The method was validated in terms of linearity, carryover, recovery, precision, accuracy and stability. Extraction yield was also determined for accurate evaluation of vitamin E content in human breast adipose tissue samples. Finally, concentrations of particular tocochromanols compounds were assessed in human breast adipose tissue samples obtained from 99 patients, including women with breast cancer, healthy volunteers and deceased women who had died as a result of accidents. The raw data was transformed according to the newly developed equation for accurate estimation of the concentrations of tocochromanols in breast adipose tissue samples. Results obtained in the study indicated that the proposed analytical assay could be useful in breast cancer research.

HPLC-APCI-MS/MS method development and validation for determination of tocotrienols in human breast adipose tissue.

For the last decade, significant attention has been paid to the potential role of tocotrienols in prevention and therapy of breast cancer. Therefore, the aim of this study was to develop and validate analytical method for quantitative determination of tocotrienols (α-, ß-, γ- and δ-tocotrienol) in human breast adipose tissue with the use of high performance liquid chromatography coupled with APCI-MS/MS detection. Separation of target compounds was achieved within 10min with the use of naphthylethyl Cosmosil 2.5π-NAP column with methanol/water mixture (90:10, v/v) under isocratic elution. Adipose tissue samples were obtained from breast cancer patients and women deceased as a result of accidents. Sample preparation procedure was optimized with the application of the Plackett-Burman design and included tissue homogenization with the use of isopropanol/ethanol/aqueous 0.1% FA mixture (13:3:8, v/v), centrifugation and solid phase extraction (SPE). The method was validated in terms of linearity, precision, accuracy, stability (bench top, autosampler, postpreparative, freeze and thaw stability), matrix effect (ME), recovery (RE) and process efficiency (PE). As for all four tocotrienols ME was negligible (< 15%), precision and accuracy tests were performed with the use of tocotrienols' standard solutions within the ranges of 10.0-400.0ng/g for all four tocotrienols. As the validation requirements were met, the validated method was applied for quantitative analysis of tocotrienols in breast cancer patients.

Analysis of postoperative morbidity and mortality following surgery for gastric cancer. Surgeon volume as the most significant prognostic factor.

INTRODUCTION: Surgical resection is the only potentially curative modality for gastric cancer and it is associated with substantial morbidity and mortality. AIM: To determine risk factors for postoperative morbidity and mortality following major surgery for gastric cancer. MATERIAL AND METHODS: Between 1.08.2006 and 30.11.2014 in the Department of Oncological Surgery of Gdynia Oncology Centre 162 patients underwent gastric resection for adenocarcinoma. All procedures were performed by 13 surgeons. Five of them performed at least two gastrectomies per year (n = 106). The remaining 56 resections were done by eight surgeons with annual volume lower than two. Perioperative mortality was defined as every in-hospital death and death within 30 days after surgery. Causes of perioperative deaths were the matter of in-depth analysis. RESULTS: Overall morbidity was 23.5%, including 4.3% rate of proximal anastomosis leak. Mortality rate was 4.3%. Morbidity and mortality were not dependent on: age, gender, body mass index, tumour location, extent of surgery, splenectomy performance, or pTNM stage. The rates of morbidity (50% vs. 21.3%) and mortality (16.7% vs. 3.3%) were significantly higher in cases of tumour infiltration to adjacent organs (pT4b). Perioperative morbidity and mortality were 37.5% and 8.9% for surgeons performing less than two gastrectomies per year and 16% and 0.9% for surgeons performing more than two resections annually. The differences were statistically significant (p = 0.002, p = 0.003). CONCLUSIONS: Annual surgeon case load and adjacent organ infiltration (pT4b) were significant risk factors for morbidity and mortality following major surgery for gastric cancer. The most common complications leading to perioperative death were cardiac failure and proximal anastomosis leak.

VEGF, Flt-1, and microvessel density in primary tumors as predictive factors of colorectal cancer prognosis.

Angiogenesis in the primary tumor is known to be necessary for tumor progression in adenocarcinomas of the colon. However, whether angiogenesis in the primary tumors of patients with colorectal cancer affects their prognosis has yet to be fully elucidated. The aim of the present study was to assess the association between selected pathoclinical parameters and overall survival of resectable colorectal cancer patients with the expression of angiogenesis-promoting factors, including vascular endothelial growth factor (VEGF) and Fms-like tyrosine kinase receptor (Flt-1), and microvessel density (MVD) in the primary tumor. VEGF and Flt-1 expression were assessed, as well as MVD (with anti-CD34) by immunohistochemistry in 139 archived primary colorectal cancer tissue samples. These results were compared with the overall survival of the patients and potential prognostic pathoclinical parameters. A higher MVD in the tumors expressing Flt-1 (P=0.04) was identified. However, there was no correlation between the pathoclinical parameters of colon cancer and Flt-1 expression, VEGF expression, or MVD in the tumor. Furthermore, the intensity of VEGF expression, Flt-1 expression and tumor MVD did not correlate with the overall survival of the patients. Therefore, although increased expression of VEGF and Flt-1 was correlated with an increased expression of MVD in the primary tumors of resectable colorectal cancer patients, these factors were not correlated with prognostic pathoclinical factors and overall survival.

Same Quality of Life for Polish Breast Cancer Patients Treated with Mastectomy and Breast Reconstruction or Breast-Conserving Therapy.

Breast cancer often requires combined oncologic treatments, the base of which is surgery. Quality of life (QoL) after each surgical procedure may influence the process of decision making among women, who qualify for multiple oncological strategies. Our knowledge about QoL in breast cancer patients is derived from comparative studies. Results may differ, depending on country, culture, and societal relations. The aim of the study was to investigate the quality of life of Polish patients treated with breast-conserving therapy (BCT) or mastectomy with breast reconstruction. MATERIAL AND METHODS: The study involved women who underwent surgery for breast cancer in the Department of Surgical Oncology of the Gdynia Oncology Center from September 2010 to November 2013. Eighty-two breast reconstructions (in 79 patients) and 226 BCT procedures were performed. QoL was measured with the use of EORTC QLQ-C30 and QLQ-BR23 questionnaires. RESULTS: Global QoL was high in both groups and did not differ significantly. Body image was slightly better after BCT than after mastectomy with breast reconstruction, but sexual QoL was lower. Future perspective was quite low in both groups. Disease symptoms were not bothering. CONCLUSIONS: The global QoL among Polish breast cancer patients treated with BCT or mastectomy with breast reconstruction is high and does not differ between groups. There is a need for anxiety and disease-related fear prophylaxis and for the improvement of sex life of breast cancer survivors.

Medium-chain triglycerides/long-chain triglycerides versus long-chain triglycerides in treatment of cancer patients with major body mass loss. Survival in patients with refractory cachexia.

INTRODUCTION: Currently there are no established guidelines regarding the use of long-chain triglycerides (LCT) vs. medium-chain triglycerides medium-chain triglycerides (MCT)/long-chain triglycerides (LCT) in total parenteral nutrition (TPN). Severe malnutrition of patients with refractory cachexia (RC) often causes their disqualification from invasive methods of treatment thus decreasing their quality of life and survival time. AIM: To compare the changes in nutritional state of patients with RC receiving PN with LCT and LCT/MCT lipid emulsions and to assess the influence of enteral nutrition on their survival time. MATERIAL AND METHODS: The study group comprised of 50 patients (23 female, 27 male) with a median age of 66 years. Refractory cachexia was diagnosed in them due to dysphagia secondary to solid tumours causing obstruction of the gastrointestinal tract (GT). All patients were qualified for surgical gastrostomy due to contraindications to percutaneous endoscopic gastrostomy. The patients were randomly assigned into one of two groups and perioperatively received either LCT or LCT/MCT. Blood samples were collected four times and tested for: total protein, albumin, prealbumin, and C-reactive protein concentration. Patients received Home Enteral Nutrition after discharge from hospital. RESULTS: Changes in nutritional status parameters were similar among patients receiving lipid emulsions LCT vs. MCT/LCT in TPN for 11 days. The mean survival time of all patients operated to gain enteral access to nutrition was 192 ±268 days, and the median survival was 98 days. CONCLUSIONS: Regarding the short-term TPN, the results of the study do not demonstrate any superiority of MCT/LCT lipid emulsions over LCT, or vice versa. The inability to eat significantly accelerates unintended body mass loss among patients with RC. Disqualification from invasive treatment options deprives some patients of the benefits they might have obtained from the surgical access to GT and enteral nutrition.

Enteral feeding and its impact on the gut immune system and intestinal mucosal barrier.

Enteral feeding is the preferred method of nutritional therapy. Mucosal lack of contact with nutrients leads do lymphoid tissue atrophy, immune system functional decline, and intensification in bacterial translocation. Currently, it is assumed that microbiome is one of the body organs that has a significant impact on health. The composition of microbiome is not affected by age, sex, or place of residence, although it changes rapidly after diet modification. The composition of the microbiome is determined by enterotype, which is specific for each organism. It has a significant impact on the risk of diabetes, cancer, atherosclerosis, and other diseases. This review gathers data on interaction between gut-associated lymphoid tissue, mucosa-associated lymphoid tissue, microbiome, and the intestinal mucosal barrier. Usually, the information on the aforementioned is scattered in specialist-subject magazines such as gastroenterology, microbiology, genetics, biochemistry, and others.

Factors influencing the eicosanoids synthesis in vivo.

External factors activate a sequence of reactions involving the reception, transduction, and transmission of signals to effector cells. There are two main phases of the body's reaction to harmful factors: the first aims to neutralize the harmful factor, while in the second the inflammatory process is reduced in size and resolved. Secondary messengers such as eicosanoids are active in both phases. The discovery of lipoxins and epi-lipoxins demonstrated that not all arachidonic acid (AA) derivatives have proinflammatory activity. It was also revealed that metabolites of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) such as resolvins, protectins, and maresins also take part in the resolution of inflammation. Knowledge of the above properties has stimulated several clinical trials on the influence of EPA and DHA supplementation on various diseases. However, the equivocal results of those trials prevent the formulation of guidelines on EPA and DHA supplementation. Prescription drugs are among the substances with the strongest influence on the profile and quantity of the synthesized eicosanoids. The lack of knowledge about their influence on the conversion of EPA and DHA into eicosanoids may lead to erroneous conclusions from clinical trials.

The HER2 gene and HER2 protein status and chromosome 17 polysomy in gastric cancer cells in own material.

BACKGROUND: The aims of the study were to assess the expression of HER2 protein, the amplification of the HER2 gene, and the occurrence of chromosome 17 polysomy in gastric cancer cells and to analyze the relation between the results of such a determination and the selected clinicopathologic parameters in patients treated for gastric cancer. METHODS: Tissue samples of primary tumor from 83 consecutive patients who underwent gastric cancer resection were analyzed by immunohistochemical (IHC) analysis and fluorescence in situ hybridization (FISH). RESULTS: A positive result of the IHC test, with a minimum score +, was obtained among 22.8% patients. The FISH test was carried out successfully among 58 patients, including 10.3% cases with a positive result, whereas the presence of chromosome 17 polysomy was confirmed among 13.8% patients. A statistically significant dependence was found between the presence of HER2 overexpression and: the lower stage of tumor infiltration, the higher grade of cancer differentiation, no mucinous component, and the intestinal type according to the Lauren classification. Statistically significant relation was found between chromosome 17 polysomy and the tumor location in the proximal part of the stomach, the performance of the palliative procedure, the presence of distant metastases, and a higher frequency of postoperative complications. CONCLUSIONS: There is no complete coincidence in gastric cancer between the occurrence of the HER2 gene amplification and the HER2 receptor expression. The impact of the HER2 gene status and HER2 protein on prognosis in gastric cancer remains unclear. Chromosome 17 polysomy may be an important negative prognostic factor in gastric cancer.

VEGF-C expression is not a prognostic factor in locally advanced colon adenocarcinoma.

AIM OF THE STUDY: Evaluation of the relationships between increased expression of VEGF-C (vascular endothelial growth factor-C) and vessel density in the tumour-surrounding stroma, patient survival, and other conventional prognostic factors in patients with pT3-4 colon cancer. MATERIAL AND METHODS: Expression of VEGF-C and vessel density were immunohistochemically assessed in 104 specimens of primary, locally advanced (pT3-4) colon adenocarcinoma after surgical resection. RESULTS: A significant relationship was found between the expression of VEGF-C and increased vessel density in the tumour-surrounding stroma (p = 0.03). A relationship between VEGF-C expression and location of the tumour in the left side of the colon was also found (p = 0.003). Expression of VEGF-C was likely to occur in well-differentiated tumours. No relationship between patient overall survival and the expression level of VEGF-C in locally advanced colon cancer was observed. CONCLUSIONS: The study results indicate that expression of VEGF-C in cells of locally advanced pT3-4 adenocarcinoma of the colon does not affect the survival time of the patients. Increased expression of VEGF-C is accompanied by a significant increase in vessel density in the pT3-4 tumour stroma. Increased expression of VEGF-C in cancer cells is related to the tumour location in the left side of the colon and better tumour differentiation.

Endoscopic methods in the treatment of early-stage esophageal cancer.

Most patients with early esophageal cancer restricted to the mucosa may be offered endoscopic therapy, which is similarly effective, less invasive and less expensive than esophagectomy. Selection of appropriate relevant treatment and therapy methods should be performed at a specialized center with adequate facilities. The selection of an endoscopic treatment method for high-grade dysplasia and early-stage esophageal adenocarcinoma requires that tumor infiltration is restricted to the mucosa and that there is no neighboring lymph node metastasis. In squamous cell carcinoma, this treatment method is accepted in cases of tumors invading only up to the lamina propria of mucosa (m2). Tumors treated with the endoscopic method should be well or moderately differentiated and should not invade lymphatic or blood vessels. When selecting endoscopic treatments for these lesions, a combination of endoscopic resection and endoscopic ablation methods should be considered.

Primary osteosarcoma of the breast: A case report.

Osteosarcoma (OS) located in the breast is an extremely rare, malignant neoplasm. The current study presents the diagnostic process, treatment and follow-up of a 67-year-old female with OS of the breast. The diagnosis was made according to diagnostic imaging methods and microscopic examination with additional immunohistochemical staining. As a surgical treatment, tumourectomy with intraoperative histological examination and simple breast amputation was performed. No adjuvant chemotherapy was administered following surgery. Lung and bone metastases occurred without local recurrence 14 months following the surgery. In the present study, the details of the diagnostic examinations performed are evaluated and the consecutive phases of diagnostic and therapeutic proceedings are examined in comparison with the knowledge in the literature.

Multiple colon perforation as a fatal complication during treatment of metastatic melanoma with ipilimumab - case report.

Ipilimumab, an anticancer drug, is an anti-CTLA4 monoclonal antibody. It is used in treatment of disseminated melanoma. Therapy is associated with high risk of complications. One of the most serious, although one of the rarest is perforation of gastrointestinal tract. In this case report we describe a 52-year old male, with disseminated melanoma with unknown starting point, treated with anti- CTLA4 monoclonal antibody. After 3rd dose of drug administration, bloody diarrhea and acute abdominal pain occurred as a symptom of gastrointestinal perforation. A single perforation was sutured during laparotomy. Symptoms of acute abdomen returned after 10 days. Pus-faecalperitonitis, symptoms of necro-hemorrhagic colitis and multilocal perforation of the colon were found during relaparotomy. Pancolectomy with end ileostomy was performed. Few hours since relaparotomy pacient died due to multiple organ failure. The purpose of this case report is to draw attention to a risk of multilocal colon perforation in patient treated with ipilumumab.