The effect of visceral reception activation (water load test) on autonomic activity and gastric myoelectric activity in gastrointestinal malignancies.

OBJECTIVES: The aim of this study was to analyze the effect of water load test (WLT) on heart rate variability (HRV), blood pressure variability (BPV), hemodynamic parameters and gastric myoelectric activity in gastrointestinal (GI) cancer patients. BACKGROUND: WLT activates gastrointestinal mechanoreception and osmoreception, and hence, can indirectly modulate autonomic activity. METHODS: Eighty patients (mean age 61.2 years) were enrolled, along with the group of healthy controls. HRV, BPV and electrogastrography (EGG) were recorded at rest (in a fasted state) and after water uptake at 100 ml/min. RESULTS: WLT contributed to an increase in the percentages of normogastria time, from 37.3 % to 50.0 % (p=0.02) and from 42.3 % to 47.7 % (p=0.01), respectively in colon and rectal cancer. Cancer patients presented lower values of HRV indices determined on linear analysis at rest and after WLT. CONCLUSIONS: A slight predominance of the sympathetic component was observed in response to WLT, which was reflected by changes in hemodynamic parameters. The response to WLT is a consequence of GI mechanoreception and osmoreception activation and resultant pressure reaction. This effect was disrupted by the neoplastic process within the GI tract, especially in gastric and colon malignancies, but not in rectal cancer (Tab. 2, Fig. 12, Ref. 40). Text in PDF www.elis.sk Keywords: autonomic nervous system, gastric myoelectric activity, water uptake, heart rate variability, blood pressure variability, gastrointestinal cancer.

Hippo pathway - brief overview of its relevance in cancer.

The Hippo pathway is the major regulator of organ growth and proliferation. Described initially in Drosophila, it is now recognized as one of the most conserved molecular pathways in all metazoan. Recent studies have revealed the Hippo signalling pathway might contribute to tumorigenesis and cancer development. The core components of the Hippo pathway include the mammalian sterile 20-like kinases (MSTs), large tumour suppressor kinases (LATSs), the adaptor proteins Salvador homologue 1 (SAV1, also called WW45) and Mps One Binder kinase activator proteins. The major target of the Hippo core kinases is the mammalian transcriptional activator Yes-associated protein (YAP) and transcriptional co-activator with PDZ-binding motif (TAZ). In cancer, the Hippo signalling is inactivated and YAP and TAZ are activated and free to translocate into the nucleus to promote cell proliferation. Nuclear YAP/TAZ activate or suppress transcription factors that regulate target genes involved in cell proliferation, tissue growth, control of organ size and shape or metastasis. The Hippo signalling pathway that controls the most important cellular processes like growth and division appears to be a very promising research subject in the field of cell biology and tissue engineering. It consists of elements that in the cell play the roles of tumour suppressors as well as oncogenes. This 'Janus like' - an opposite activity hidden within one and the same signalling pathway represents a significant obstacle for studying it. This property of the Hippo pathway is worth remembering, as it will appear several times during the discussion of its properties. Here, we will review certain data regarding biology of the Hippo signalling and its interplay with other prominent signalling pathways in the cell, its relevance in cancer development and therapies that might target elements of the Hippo pathway in most human cancers.

Enterohormonal disturbances in colorectal cancer patients.

Gastrointestinal (GI) hormonal peptides play a role in the development of gastrointestinal malignancies, and their abnormal levels may contribute to dysmotility. The aim of this study was to analyze plasma concentrations of enterohormones (motilin, ghrelin, gastrin and pancreatic polypeptide) and to verify if their abnormal levels may contribute to the severity of dyspeptic symptoms in colorectal cancer patients. The study included 60 patients with colorectal malignancies (22 men and 38 women), among them 30 individuals with colon cancers (group A) and 30 subjects with rectal tumors (group B). Fasting plasma levels of pancreatic polypeptide (PP), motilin, gastrin and ghrelin were determined by means of ELISA. The results were compared with the respective parameters of healthy volunteers. Colon cancer patients presented with significantly lower concentrations of ghrelin than the subjects with rectal tumors and healthy controls (156.8±86.7 vs. 260.2±87.6 vs. 258.4±94.2 pg/ml, p=0.02), as well as with significantly higher levels of PP (265.5±66.3 vs. 154.1±54.6 vs. 148.3±64.3 pg/ml, p=0.005). Also the levels of motilin turned out to be lower in colon cancer patients than in the subjects with rectal malignancies and healthy controls. No statistically significant intergroups differences were found in plasma levels of gastrin (388.2±98.6 vs. 475.6±88.7 vs. 428.2±91.2 pg/ml, p>0.05). Epigastric bloating was the most frequent dyspeptic symptom, reported by 63.3% and 40% of patients with colon and rectal tumors, respectively. Our findings imply that colon cancer patients may present with abnormal plasma levels of enterohormones significantly more often than individuals with rectal malignancies. Dysmotility observed in colon cancer patients may result not only from anticancer surgery, but also from abnormal release of enterohormones, induced either by neoplastic process or by changes within the autonomic nervous system.

Electroneurography in the evaluation of oxaliplatin-induced neuropathy in colorectal cancer patients.

Cold-induced neuropathy is the most observed side effect of oxaliplatin. Presence of neuropathy is routinely assessed by electroneurographical examination. The use of electroneurography has not been a part of typical oncological monitoring and treatment protocols, leading to untreated, irreversible damage to patients' peripheral nerves, undiagnosed for long periods of time. 36 colorectal cancer patients followed FOLFOX4 with/without bevacizumab or XELOX were enrolled between February 2013 and January 2015 in the study at the University Hospital Oncological Department, Krakow, Poland. Electroneurography was performed prior to the first cycle of chemotherapy and after the 4th cycle. 32 out of 36 enrolled patients completed neurological evaluation. Pre-treatment neurographic examination revealed presence of peripheral neuropathy in 10 (31.25%) patients; 6 (18.75%) had sensory neuropathy and 4 (12.5%) had mixed, sensorimotor neuropathy. After treatment examination revealed significant increase in the number of neuropathic patients; presence of peripheral neuropathy was observed in 19 patients (59%), sensory polyneuropathy was diagnosed in10 patients (31.25%) and mixed neuropathy was diagnosed in 9 patients (28.13%). Early electrophysiological monitoring followed by a symptom dependent oxaliplatin regimen would be highly beneficial for patients undergoing oxaliplatin treatment, improving their well-being and positively affecting their life quality.

Salvage chemotherapy in metastatic colorectal cancer with the combination of capecitabine and mitomycin C.

A significant proportion of heavily pretreated patients with metastatic colorectal cancer maintain good performance status (PS) and are eligible for further systemic treatment. Mitomycin C (MMC) combined with capecitabine can be considered as salvage treatment in this group of patients. To evaluate the efficacy and toxicity of mitomycin C and capecitabine as at least third-line systemic therapy (after failure of 5Fu, irinotecan, oxaliplatin-based chemotherapy regimens and targeted therapies) in patients with metastatic colorectal cancer. A total of 31 patients with a median age of 55.2 years with metastatic colorectal cancer received salvage chemotherapy at the Oncological Department of University Hospital in Krakow, Poland, between July 2011 and July 2014. Chemotherapy consisted of intravenous MMC 6 mg/m2 on day 1 and oral capecitabine 1000 mg/m2 twice daily on days 1-14 followed by a 7-day treatment-free interval. Each cycle was repeated every 3 weeks unless there was evidence of disease progression or unacceptable toxicity. All the31 patients were evaluable for response and toxicity. A total of 113 cycles were administered. Five of the 31 (16.1%) patients had stable disease after three cycles of chemotherapy, 24 (77.4%) patients progressed and 1 (3.2%) patient is still undergoing treatment. One patient (3.2%) died due to cardiac infarct 5 days after starting treatment. Median progression free survival (PFS) was 2.5 months. Median overall survival (OS) was 4.9 months. Toxicity was mild and easily manageable. Mitomycin C and capecitabine can be considered as salvage therapy in heavily pretreated patients with metastatic colorectal cancer and with good performance status. Toxicity of these drugs combination is moderate and easily manageable.