Novel Diagnostic Biomarkers in Colorectal Cancer.

Colorectal cancer (CRC) is still a leading cause of cancer death worldwide. Less than half of cases are diagnosed when the cancer is locally advanced. CRC is a heterogenous disease associated with a number of genetic or somatic mutations. Diagnostic markers are used for risk stratification and early detection, which might prolong overall survival. Nowadays, the widespread use of semi-invasive endoscopic methods and feacal blood tests characterised by suboptimal accuracy of diagnostic results has led to the detection of cases at later stages. New molecular noninvasive tests based on the detection of CRC alterations seem to be more sensitive and specific then the current methods. Therefore, research aiming at identifying molecular markers, such as DNA, RNA and proteins, would improve survival rates and contribute to the development of personalized medicine. The identification of "ideal" diagnostic biomarkers, having high sensitivity and specificity, being safe, cheap and easy to measure, remains a challenge. The purpose of this review is to discuss recent advances in novel diagnostic biomarkers for tumor tissue, blood and stool samples in CRC patients.

Changes in plasma levels of cholecystokinin, neurotensin, VIP and PYY in gastric and colorectal cancer - Preliminary results.

Physiological roles of enterohormones such as secretion, absorption and digestion were supported by clinical data. Overexpression of cholecystokinin (CCK), neurotensin (NT) and vasoactive intestinal peptide (VIP) receptors occur in gastrointestinal (GI) malignancies. The aim of the paper was to compare plasma levels of CCK, peptide YY (PYY), VIP and NT in patients with gastrointestinal malignancies and healthy controls. The study included 80 patients (37 men and 43 women) with GI malignancies (20 with gastric and 60 with colorectal cancers). Median age of the patients was 62.9 years (range: 40-85 years). Control group was comprised of 30 healthy persons with median age 59.8 years (range: 40-82 years). Fasting plasma concentrations of CKK, PYY, NT, and VIP were determined at rest, using ELISA kits for automated systems. Comparative analysis of enterohormone levels in patients with various types of gastrointestinal malignancies demonstrated presence of some cancer-specific alterations. Patients with gastric cancers presented with lower plasma concentrations of CCK than healthy controls and individuals from colorectal cancers (p = 0.02). The highest plasma concentrations of neurotensin was found in colorectal cancer patients in comparison to gastric (p = 0.02). The plasma levels of VIP observed in gastric cancer group were lower than in colorectal cancer patients (p = 0.01). Patients with GI malignancies may present with tumor-specific alterations in plasma enterohormone levels.

Association between gastric myoelectric activity disturbances and dyspeptic symptoms in gastrointestinal cancer patients.

PURPOSE: Dyspeptic symptoms present a severe problem in gastrointestinal (GI) cancer patients. The aim of the study was to analyze an association between gastric myoelectric activity changes and dyspeptic symptoms in gastrointestinal cancer patients. MATERIAL AND METHODS: The study included 80 patients (37 men and 43 women, mean age 61.2 ± 7.8 years) diagnosed with GI tract malignancies: colon (group A), rectal (group B) and gastric cancers (group C). Gastric myoelectric activity in a preprandial and postprandial state was determined by means of a 4-channel electrogastrography. Autonomic nervous system was studied based on heart rate variability analysis. The results were compared with the data from healthy asymptomatic controls. RESULTS: In a fasted state, GI cancer patients presented with lesser percentages of normogastria time (A:44.23 vs. B:46.5 vs. C:47.10 vs. Control:78.2%) and average percentage slow wave coupling (ACSWC) (A:47.1 vs. B:50.8 vs. C:47.2 vs. Control:74.9%), and with higher values of dominant power (A:12.8 vs. B:11.7 vs. C:12.3 vs. Control:10.9) than the controls. Patients did not show an improvement in the percentage of normogastria time, dominant power, dominant frequency and ACSWC in response to food. The severity of dyspeptic symptoms correlated with the values of electrogastrography parameters. Patients showed lower values of heart rate variability parameters than the healthy controls, that indicate abnormal autonomic nervous system activity. CONCLUSION: GI cancers affect the gastric myoelectric activity, decreasing normogastria and slow wave coupling. These patients do not show adequate gastric motility response to food. Impaired gastric electric motility may result from cancer-induced autonomic disturbances.

Oxaliplatin treatment and peripheral nerve damage in cancer patients: A Polish cohort study.

INTRODUCTION: Oxaliplatin-induced neurotoxicity is the single main dose-limiting factor in the treatment of colorectal cancer. The degree of neurotoxicity may be either acute and reversible or observed as cumulative and chronic peripheral nerve damage leading to peripheral neuropathy (PNP), walking difficulties, extremity hypersensitivity, tingling and numbness, and increased pain sensation. AIM: The aim of this paper is to determine and compare the ratio of clinical versus subclinical PNP cases in colorectal patients who underwent oxaliplatin treatment. MATERIALS AND METHODS: Thirty-two colorectal cancer patients were enrolled in the study. Patients received chemotherapy either as folinic acid and 5-fluorouracil and oxaliplatin or capecitabine and oxaliplatin regimen. Electroneurophysiological tests were performed before the treatment and after the 4th cycle when the risk of peripheral nerve damage increases. All patients were subject to a standard neurological examination and a semi-structured questionnaire interview. RESULTS AND DISCUSSION: Following oxaliplatin treatment, 21 (66.6%) of all patients presented neurological symptoms and/or electrophysiologically measured signs of PNP; of those, 7 patients (33.4%) displayed only electrophysiological changes and the remaining 14 patients (66.6%) presented fully symptomatic PNP - 4 patients were new neuropathy cases while the other 10 patients were previously diagnosed with PNP and showed signs of further neuronal deterioration and progressing sensory and motor dysfunction. CONCLUSION: Our study lays ground for further larger scale longitudinal studies on oxaliplatin neurotoxicity and its prevention. We believe that early diagnosis of oxaliplatin-induced neurotoxicity is essential in the prevention of irreversible nerve damage and should be prioritized when assessing and evaluating treatment so that adequate adjustment may be made.

Autonomic dysregulation in colon cancer patients.

To the best of our knowledge, only two studies analyzed the relationship between HRV and carcinoembryonic antigen (CEA) in colon cancer patients. The aim of this study was to analyze changes in the autonomic activity of colon cancer patients using heart rate variability (HRV) and blood pressure variability (BPV) measures, and to verify if HRV and BPV parameters correlate with hemodynamic indices in this group and the plasma levels of CEA. Presence of colon cancer is associated with changes in autonomic activity, namely parasympathetic-sympathetic imbalance in form of sympathetic overdrive. Cancer-related autonomic dysfunction may contribute to impairment of gastrointestinal motility.

Sunitinib-induced hypothyroidism predicts progression-free survival in metastatic renal cell carcinoma patients.

Sunitinib is a tyrosine kinase inhibitor (TKI) used in treatment of metastatic renal cell carcinoma (mRCC), gastrointestinal stromal tumors and pancreatic neuroendocrine tumors. One of the most common side effects related to sunitinib is hypothyroidism. Recent trials suggest correlation between the incidence of hypothyroidism and treatment outcome in patients treated with TKI. This study evaluates whether development of hypothyroidism is a predictive marker of progression-free survival (PFS) in patients with mRCC treated with sunitinib. Twenty-seven patients diagnosed with clear cell mRCC, after nephrectomy and in 'good' or 'intermediate' MSKCC risk prognostic group, were included in the study. All patients received sunitinib as a first-line treatment on a standard schedule (initial dose 50 mg/day, 4 weeks on, 2 weeks off). The thyroid-stimulating hormone serum levels were obtained at the baseline and every 12 weeks of treatment. In statistic analyses, we used Kaplan-Meier method for assessment of progression-free survival; for comparison of survival, we used log-rank test. In our study, the incidence of hypothyroidism was 44%. The patients who had developed hypothyroidism had better median PFS to patients with normal thyroid function 28,3 months [95% (CI) 20.4-36.2 months] versus 9.8 months (6.4-13.1 months). In survival analysis, we perceive that thyroid dysfunction is a predictive factor of a progression-free survival (PFS). In the unified group of patients, the development of hypothyroidism during treatment with sunitinib is a positive marker for PFS. During that treatment, thyroid function should be evaluated regularly.

Chemotherapy-induced neuropathies-a growing problem for patients and health care providers.

INTRODUCTION: Chemotherapy-induced neuropathies are one of the most common side effects of cancer treatment, surpassing bone marrow suppression and kidney dysfunction. Chemotherapy effects on the nervous system vary between different classes of drugs and depend on specific chemical and physical properties of the drug used. The three most neurotoxic classes of anti-cancer drugs are: platinum-based drugs, taxanes, and thalidomide and its analogs; other, less neurotoxic but also commonly used drugs are: bortezomib, ixabepilone, and vinca alkaloids. METHODS: Here, in this paper, based on our experience and current knowledge, we provide a short review of the most common, neuropathy-inducing anti-cancer drugs, describe the most prevalent neuropathy symptoms produced by each of them, and outline preventive measures and treatment guidelines for cancer patients suffering from neuropathy and for their health care providers. RESULTS: Patients should be encouraged to report any signs of neuropathic pain, alteration in sensory perception, tingling, numbness, burning, increased hot/cold sensitivity and motor dysfunctions as early as possible. If known neurotoxic chemotherapeutics are used, a neurological examination with electrophysiological evaluation should be implemented early in the course of treatment so, both patients and physicians would be better prepared to cope with possible neurotoxic effects. CONCLUSIONS: The use of neurotoxic chemotherapeutics should be closely monitored and if clinically permitted, that is, if a patient shows signs of cancer regression, drug doses should be reduced or combined with other less neurotoxic anti-cancer medication. If not counteractive, the use of over the counter antineuropathic supplements such as calcium or magnesium might be encouraged. If physically possible, patients should also be encouraged to exercise regularly and avoid factors that might increase nerve damage such as excessive drinking, smoking, or sitting in a cramped position.

Evaluation of health-related quality of life and its main influencing factors in a Polish population of patients with bone metastases.

PURPOSE: Regardless of cancer type, the skeleton is one of the most common sites for cancer spread. Health-related Quality of Life (HRQoL) can be considered a primary endpoint in clinical trials concerning cancer patients with palliative disease. The proper measurement of this endpoint requires valid and reliable instruments. The aim of this study was to evaluate HRQoL and its main influencing factors using validated EORTC tools - the QLQ-C30 and the QLQ-BM22 in Polish population of patients with skeletal metastases. METHODS: Patients with bone metastases and histologically confirmed malignancy were qualified for the study. They filled out a personal questionnaire, the Polish version of the EORTC QLQ-C30 and its supplementary module QLQ-BM22. The influence of numerous socio-clinical factors such as age, gender, working status, level of education, performance status, primary location, and previous treatment received was assessed. RESULTS: One hundred and ten patients (65 women) were enrolled into this study (mean age ±SD; 57.8±13.8). The most significant HRQoL issues were fatigue (59.29/100); pain (56.97/100) and insomnia (56.36/100). Men coped worse with pain (p=0.013), fatigue (p=0.050), nausea and vomiting (p=0.024) and financial difficulties (p=0.016) than women. CONCLUSIONS: The main factors influencing HRQoL in Polish patients with bone metastases are fatigue, pain and insomnia, and as such should be a primary focus of patient-centered care in this group.

Macrocytosis during sunitinib treatment predicts progression-free survival in patients with metastatic renal cell carcinoma.

Sunitinib, a multi-targeted receptor tyrosine kinase inhibitor, is a first-line treatment for metastatic renal cell carcinoma (mRCC) in patients in 'low' and 'intermediate' Memorial Sloan Kettering Cancer Center and Heng risk groups. Disruptions of hematopoiesis, such as anemia, neutropenia, and thrombocytopenia, are typically observed during sunitinib treatment. When it comes to RBC parameters, an increase in mean cell volume (MCV) tends to occur, meeting the criteria for macrocytosis in some patients (MCV > 100 fL). We examined changes in RBC parameters of 27 mRCC patients treated with sunitinib (initial dose of 50 mg/day, 6-week treatment: 4 weeks on, 2 weeks off) and correlated them with progression-free survival time (PFS). Patients who had macrocytosis after 3 treatment cycles had significantly longer PFS than those whose MCV stayed less than 100 fL (not reached vs. 11.2 months, p < 0.001). We also found a correlation between MCV values after the first and third treatment cycles and the risk of progression: HR of 0.9 (0.81-0.99) and 0.76 (0.65-0.90) per 1 fL increase in MCV, respectively. The mechanism of MCV elevation during sunitinib treatment has not yet been fully explained. One of the probable causes is sunitinib's inhibitory influence on c-Kit kinase, as is the case with imatinib. For mRCC patients, this phenomenon could help predict PFS, but since our sample was small, further studies are essential.

Bradycardia as a rare symptom of cisplatin cardiotoxicity: A case report.

Cisplatin (DDP) is one of the most frequently used chemotherapeutic agents, and has a characteristic toxicity profile. For DDP, complications affecting the cardiovascular system, which are typical for certain other agents, are rare; however, their occurrence may lead to life-threatening conditions. To the best of our knowledge, there are few reported cases of DDP-induced bradycardia in the relevant medical literature. The current report presents the case of a 58-year-old patient diagnosed with metastatic neuroendocrine carcinoma with a primary lesion in the posterior mediastinum, who was treated with DDP and etoposide chemotherapy. Following the initial chemotherapy cycle, the patient experienced severe symptomatic bradycardia (a drop in heart rate to 40 bpm), with the corrected QT interval prolonged to 424 msec. The patient's condition required close monitoring and treatment. Similar symptoms occurred following each of the three cycles of chemotherapy. Imaging studies performed following the third treatment cycle revealed disease progression, and the patient was referred for palliative care. Reports have indicated that damage to the cardiovascular system, including cardiac ischemia, diastolic disturbances, hypertension and microalbuminuria, may be associated with DDP-based therapy. However, the mechanism of DDP-associated cardiac toxicity remains to be elucidated. It may be induced by factors including direct toxicity, ion imbalance, heart infiltration and, in the case of neuroendocrine tumors, the influence of tumor excretions.

Synchronous extraskeletal Ewing's sarcoma/PNET and gallbladder carcinoma: a case report and literature review.

Ewing's sarcoma (ES) and primitive neuroectodermal tumour (PNET) are now considered to be the same tumour and usually occur in long bones. Extraskeletal Ewing's sarcoma is an extremely rare neoplasm, accounting for 1% of soft tissue sarcomas, with most common location in the thorax. Gallbladder cancer (GBC) represents the most common type among the biliary tract cancers with a poor prognosis even among patients undergoing aggressive therapy. We present study of extraskeletal ES/PNET found in the hilus of the liver of an elderly, diagnosed one month prior with GBC woman. The patient underwent two cycles of chemotherapy SAIME/SAVAC for ES and thereafter was operated. During three-year follow-up no recurrence of ES/PNET has been reported. However, two years after chemotherapy the patient suffered a relapse of adenocarcinoma of the gallbladder and thus received palliative chemotherapy of gemcitabine and cisplatin. After 16 months of recurrence she died. To the best of our knowledge, this is the first case of ES/PNET located in the hilus of the liver and as a synchronous neoplasm.

Better compliance with the guidelines on hand-foot syndrome in patients treated with capecitabine in colorectal and breast cancer as a result of nursing education.

Aim: The aim of this paper is to test nursing educational intervention as a method of managing with handfoot syndrome in patients treated with capecitabine in an Eastern European setting. Design and Methods: 43 females and 49 males with colorectal and breast cancer and were treated with capecitabine monotherapy or polychemotherapy with completion of at least one cycle were enrolled for this trial in the Department of Oncology University Hospital in Krakow, between January 2011 and December 2014. Results: Patients who were in contact with their oncology nurses and followed the recommendations had a fiftyfold lower risk of developing hand-foot syndrome G2 or G3. Conclusion: Our data confirmed the role of oncology nurses in patient education process during the home-based therapies in Poland.

Pilot Testing and Preliminary Psychometric Validation of the Polish Translation of the EORTC INFO25 Questionnaire: Validation of the Polish version of INFO25-pilot study.

The quality of information that oncological patients receive from health care professionals is an underestimated issue in Poland and Eastern European countries. There is lack of sufficient data on this subject. The European Organization for Research and Treatment of Cancer (EORTC) supplies a new tool for measuring the quality of information provided to cancer patients. The purpose of the study is the translation into Polish, pilot testing and preliminary validation of the EORTC information module (INFO25). Following the EORTC translation procedures, forward and back translations of the questionnaire were performed (English → Polish, Polish → English). The intermediate version of the INFO25 was pilot-tested together with the general questionnaire of quality of life (EORTC QLQ-C30). Reliability, validity and known-group comparison tests were performed. A total of 21 patients with different cancer diagnoses were recruited into the study (7 women and 14 men; mean age of 60,2 years, age range 25-73 years). Apart from filling out the INFO25, patients were interviewed about the difficulties with answering every questionnaire item. Patients' comments were analyzed and minor language changes were made to the initial translation. The internal consistency of the INFO25 showed a reliability of 0,78. The final version of the Polish translation of the INFO25 module was obtained and approved by the EORTC Quality of Life Department. It can now be used in clinical setting and for scientific purposes.

Assessment of skin-related toxicity in patients with metastatic colorectal cancer treated with cetuximab.

Monoclonal antibodies (mAbs) blocking the epidermal growth factor receptor (EGFR) pathway, such as cetuximab, have been widely used in recent years for the treatment of metastatic colorectal cancer (mCRC). The purpose of this study was to evaluate the profile of the side effects of cetuximab affecting the skin and its appendages. We gathered the medical records on skin-related toxicity in 46 patients treated with cetuximab for mCRC in the Department of Clinical Oncology, University Hospital in Krakow in 2009-2013. Skin toxicity was classified according to the National Cancer Institute Common Toxicity Criteria for Adverse Events version 4.0. The typical side effects of cetuximab were observed. The most common skin toxicity was an acne-like skin rash (80% of patients) and paronychia (20%). Other side effects were trichomegaly, hypertrichosis, and allergic reactions. In view of high incidence of skin lesions during treatment with cetuximab, it is essential to observe patients carefully and to control the side effects during therapy. Previous experience from clinical trials shows that in some cases proper care and prevention can improve the quality of the patients' lives.

Oncological emergencies: tumor lysis syndrome.

Tumor lysis syndrome (TLS) occurs as a result of massive lysis of malignant cells and release of intracellular contents into the systemic circulation. It can lead to hyperuricaemia, hyperkalaemia, hyperphosphataemia and hypocalcaemia. TLS is most commonly present after initiation of anticancer therapy but it can also develop spontaneously (STLS--spontaneous tumor lysis syndrome). In the article, pathophysiology, classification, risk factors and recommendations of management in TLS, with a special focus on solid tumors, are discussed. The keys to the identification of high-risk patients, prevention and management of TLS are included in presented guidelines.

Oncological emergencies: increased intracranial pressure in solid tumours' metastatic brain disease.

Increased intracranial pressure due to metastatic brain disease is one of the oncological emergencies. It may cause herniation or insufficient brain blood flow, thus it is a life-threatening condition. This article focuses on diagnostic and treatment options, which should be introduced immediately. The prognosis remains poor.

Oncological emergencies: superior vena cava syndrome.

Superior vena cava obstruction leads to the venous hypertension of the head, neck, upper extremities and upper part of the truncus. Its clinical manifestation, known as the superior vena cava syndrome, is a complication of malignancy, mainly of lung cancer and lymphoma. As it usually affects patients with advanced disease, the prognosis is poor. This article stresses the importance of early detection and adequate management of this onco- logical emergency. The diagnostic tools as well as treatment possibilities are discussed.

Oncological emergencies: syndrome of inappropriate antidiuretic hormone secretion (SIADH).

Excessive secretion of vasopressin in the course of Syndrome of Inappropriate Antidiuretic Hormone Secretion is a common cause of hyponatremia in cancer patients. Clinical symptoms depend on the cause, rate of change of sodium level and their absolute values. Treatment options include fluid restrictions, intravenous administration of hypertonic sodium chloride solutions, loop diuretics and vaptans. The sodium level should not be adjusted too fast, because it may lead to irreversible brain damage. The article presents pathophysiology, diagnostics and recommendations of management of this oncological emergency.

The Use of Sorafenib in the Thyroid Cancer.

There are not effective therapies for metastatic unresectable, non-RAI-avid thyroid carcinomas. Fortunately, thyroid carcinomas represent a promising paradigm for targeted therapy due to the presence of activing mutations of genes coding the kinase tyrosines which are involved in all functions of cancer cells (such as: growth or invasion). In this paper an efficacy and toxicity of sorafenib, one of the multi-kinase inhibitors in thyroid carcinomas treatment is presented.