Current therapy of advanced colorectal cancer according to RAS/RAF mutational status.

Colorectal cancer is a clinically and molecularly heterogeneous disease. Currently, extended RAS and BRAF mutation testing is obligatory in routine clinical practice before starting any treatment in the metastatic setting. Treatment decision making also includes assessment of the clinical condition of the patient, definition of the treatment goal, and consideration of the primary tumor site. Biological treatment is part of the first-line drug combination unless contraindicated. Mutational status is significantly associated with the outcome of patients and is strongly predictive for anti-EGFR-targeted therapy. The prognosis of RAS mutant CRC is clearly inferior to wild-type cases. RAS remains an elusive target, and specific treatment options are not yet available. Recently, promising results of a direct KRAS G12C inhibitor have been reported; however, further confirmation is needed. The biomarker landscape in mCRC is evolving; new promising markers are awaited with the chance of more precise targeted treatment.

Resection of pancreatic cancer in Europe and USA: an international large-scale study highlighting large variations.

OBJECTIVE: Resection can potentially cure resectable pancreatic cancer (PaC) and significantly prolong survival in some patients. This large-scale international study aimed to investigate variations in resection for PaC in Europe and USA and determinants for its utilisation. DESIGN: Data from six European population-based cancer registries and the US Surveillance, Epidemiology, and End Results Program database during 2003-2016 were analysed. Age-standardised resection rates for overall and stage I-II PaCs were computed. Associations between resection and demographic and clinical parameters were assessed using multivariable logistic regression models. RESULTS: A total of 153 698 records were analysed. In population-based registries in 2012-2014, resection rates ranged from 13.2% (Estonia) to 21.2% (Slovenia) overall and from 34.8% (Norway) to 68.7% (Denmark) for stage I-II tumours, with great international variations. During 2003-2014, resection rates only increased in USA, the Netherlands and Denmark. Resection was significantly less frequently performed with more advanced tumour stage (ORs for stage III and IV versus stage I-II tumours: 0.05-0.18 and 0.01-0.06 across countries) and increasing age (ORs for patients 70-79 and ≥80 versus those <60 years: 0.37-0.63 and 0.03-0.16 across countries). Patients with advanced-stage tumours (stage III-IV: 63.8%-81.2%) and at older ages (≥70 years: 52.6%-59.5%) receiving less frequently resection comprised the majority of diagnosed cases. Patient performance status, tumour location and size were also associated with resection application. CONCLUSION: Rates of PaC resection remain low in Europe and USA with great international variations. Further studies are warranted to explore reasons for these variations.

The role of inflammation and proteinases in tumor progression.

Chronic inflammation is an important risk factor for the development of cancers. The link between chronic inflammation and the risk of developing cancer is now well established. At least 20% of all cancers arise in association with infection and chronic inflammation. Inflammation and cancer are linked both along intrinsic (driven by genetic events causing malignancy) and extrinsic (driven by inflammatory conditions predisposing to tumor) pathways. Proteinases are key contributors to the breakdown and reconstitution of extracellular matrix components in physiological processes and pathological conditions, including destructive diseases and tumor progression. Matrix metalloproteinases are especially essential in the complex process of coregulation between cellular components of the tumor environment, and they are considered as potential diagnostic and prognostic biomarkers in many types and stages of cancer. Although the link between chronic inflammation, proteinases and risk of developing cancer is now well established, several open questions remain. The most exciting challenge is to find the best approach to target cancer-associated inflammation in patients with cancer. With respect to matrix metalloproteinases, the development of a new generation of selective inhibitors is a promising area of research.

The impact of matrix metalloproteinases and their tissue inhibitors in inflammatory bowel diseases.

BACKGROUND: It has been suggested that matrix metalloproteinases (MMPs) may play a role in the pathogenesis of inflammatory bowel diseases (IBD). However, the impact of serum MMPs and their inhibitors [tissue inhibitors of metalloproteinases (TIMPs)] have scarcely been investigated in the same experimental setting in ulcerative colitis (UC) and Crohn's disease (CD) as well as their correlation with IBD activity. METHODS: MMP-2, MMP-7, MMP-9, TIMP-1 and TIMP-2 serum antigen levels were determined in 23 patients with UC, 25 patients with CD and 10 healthy control patients by enzyme-linked immunoassay technique. Statistical analysis with one-way ANOVA and Student's t tests was performed. A linear regression analysis or a Spearman's r test was used to assess correlation. Differences were considered significant with p < 0.05. RESULTS: Serum antigen concentrations of MMP-9, TIMP-1 and TIMP-2 were significantly higher in UC and CD patients compared to controls. MMP-7 was also significantly higher in CD compared with controls. Elevated MMP-9 and TIMP-1 antigen levels showed significant positive correlation with disease activity of IBD. MMP-2 and TIMP-2 levels inversely correlated with CD activity. Significant correlations were found between MMP-9/TIMP-1 and MMP-2/TIMP-2 antigen levels in both UC and CD. CONCLUSIONS: We demonstrated that serum antigen concentrations of MMP-9, TIMP-1 and TIMP-2 were significantly increased in patients with UC and CD compared to controls. Our results suggest that MMPs and TIMPs may contribute to the inflammatory and remodeling processes in IBD. Serum MMP-9 and TIMP-1 might be useful as additional biomarkers in the assessment of IBD activity.

The behavior of matrix metalloproteinases and their inhibitors in colorectal cancer.

Matrix metalloproteinases (MMPs) play an important role in the degradation of extracellular matrix components crucial for tumor growth, invasion and metastasis. MMPs are controlled by natural inhibitors called tissue inhibitors of metalloproteinases (TIMPs). We and others have demonstrated that MMPs and TIMPs are especially important in the process of tumor invasion, progression and the metastasis of colorectal cancer (CRC). It has been proposed that MMPs and TIMPs might play a part not only in tumor invasion and initiation of metastasis but also in carcinogenesis from colorectal adenomas. Several recent studies demonstrated that high preoperative serum or plasma MMP-2, MMP-9 and TIMP-1 antigen levels are strong predictive factors for poor prognosis in patients with CRC and their determination might be useful for identification of patients with higher risk for cancer recurrence. MMP-9 and TIMP-1 have significant potential tumor marker impact in CRC. Their diagnostic sensitivity is consistently higher than those of conventional biomarkers. The pharmacological targeting of CRC by the development of a new generation of selective inhibitors of MMPs, that is highly specific for certain MMPs, is a promising and challenging area for the future.

Low bone mass in microscopic colitis.

BACKGROUND: Microscopic colitis presents with similar symptoms to classic inflammatory bowel diseases. Osteoporosis is a common complication of Crohn's disease but there are no data concerning bone metabolism in microscopic colitis. AIMS: The aim of the present study was to evaluate bone density and metabolism in patients with microscopic colitis. METHODS: Fourteen patients microscopic colitis were included in the study, and 28 healthy persons and 28 age and gender matched Crohn's disease patients were enrolled as controls. Bone mineral density was measured using dual x-ray absorptiometry at the lumbar spine, femoral neck and the radius. Serum bone formation and bone resorption markers (osteocalcin and beta-crosslaps, respectively) were measured using immunoassays. RESULTS: Low bone mass was measured in 57.14% patients with microscopic colitis. Bone mineral density at the femoral neck in patients suffering from microscopic colitis and Crohn's disease was lower than in healthy controls (0.852 ± 0.165 and 0.807 ± 0.136 vs. 1.056 ± 0.126 g/cm²; p < 0.01). Bone mineral density at the non-dominant radius was decreased in microscopic colitis patients (0.565 ± 0.093 vs. 0.667 ± 0.072 g/cm²; p < 0.05) but unaffected in Crohn's disease patients (0.672 ± 0.056 g/cm²). Mean beta-crosslaps concentration was higher in microscopic colitis and Crohn's disease patients than controls (417.714 ± 250.37 and 466.071 ± 249.96 vs. 264.75 ± 138.65 pg/ml; p < 0.05). A negative correlation between beta-crosslaps concentration and the femoral and radius t-scores was evident in microscopic colitis patients. CONCLUSIONS: Low bone mass is frequent in microscopic colitis, and alterations to bone metabolism are similar to those present in Crohn's disease. Therefore, microscopic colitis-associated osteopenia could be a significant problem in such patients.

[Systemic treatment of pancreatic cancer]. / A pankreászrák szisztémás kezelése.

Pancreatic cancer is a devastating disease, survival rates did not improve during the last decades. At the same time new drugs and chemotherapy regimens have been approved for systemic use lately, the results of targeted therapy and the precision medicine approach are also encouraging. Further progress is needed covering all treatment modalities (surgery, radiotherapy, systemic treatment) in order to improve outcome of patients suffering from pancreatic cancer.

[The epidemiology of pancreatic cancer]. / A hasnyálmirigyrák epidemiológiája.

Pancreatic cancer is a relatively uncommon tumor, but even with early diagnosis, mortality rates are high, explaining why this form of cancer has now become a common cause of cancer mortality. There are no screening tests for early detection of pancreatic cancer. It is more common in men than women and is predominantly a disease of elderly people. There is wide variation in the incidence of pancreatic cancer around the world, suggesting that environmental factors are important in the pathogenesis. Smoking is the major known risk factor for pancreatic cancer, while dietary factors seem to be less important. Other possible risk factors include chronic pancreatitis, obesity and type 2 diabetes. Numerous inherited germ line mutations are associated with pancreatic cancer. Of these, hereditary pancreatitis confers the greatest risk, while BRCA2 mutations are the commonest inherited disorder. Polymorphisms in genes that control detoxification of environmental carcinogens and metabolic pathways may alter the risk of pancreatic cancer.

[Quality colonoscopy: assumptions and expectations]. / Minoségi kolonoszkópia: feltételek és elvárások.

Colonoscopy has become accepted as the most effective method of screening of the colon for neoplasia. Evidences prove that utilization of colonoscopy has increased dramatically in the past few years, largely because of increased rates of CRC screening. Effectiveness and safety of colonoscopy depend on the quality of examination, and growing body of evidence suggests that the quality of colonoscopy varies in clinical practice. Quality assurance of colonoscopy could be expected to contribute significantly to improved patient care. There is a clear need for evidence-based quality measures to ensure the quality of colonoscopy. In this review we present an overview of literature concerning criteria for best practice and important quality indicators for colonoscopy.

The surgical removal of orbital foreign bodies: double case report / A szemgödörbe került idegen testek mutéti eltávolítása két eset kapcsán

The surgical procedure of orbital foreign bodies with its complications is not yet solved in Hungary. Despite the fact that many specialities are involved, until the present day, an orbital surgical centre was not developed. The main goal of this case report is to highlight the importance of these events, to develop a surgical approach, to recognize and solve the complications if they are present even in the cases of organic foreign bodies affecting more head and neck anatomical regions and structures. Orv Hetil. 2020; 161(21): 889-894.