We examine in our study, whether the administration of Nutridrink compact rises the level of albumin and lowers the level of C-reactive protein in patients with colon cancer before the planned surgery.

The study was a retrospective one focused on individual cases that used the database of the surgical department of the Topoľčany city hospital in Slovakia. Data were collected from medical documentation of surgical department patients, including basic characteristics, laboratory, and perioperative data. This study was approved by the Ethics Commission of the Institute – World of Health, hospital Topoľčany. In Topoľčany hospital, it is recommended that patients with colorectal cancer should take enteric nutrition as part of preoperative optimisation of the nutritional condition before the planned colon resection.

The study ran from September 2015 to September 2019 and the criteria for patient spooling were as follows: age between 18 – 90 years, the diagnosis of colorectal cancer, the patient was subjected to a colorectal surgical procedure. All patients signed informed consent. The exclusive criteria were as follows: inadequate data on the patient for analysis, disapproval of the patient, non-compliance with the treatment regimen, patients who have undergone much greater surgical performance than originally planned, and patients who had already had a stoma and have previously undergone surgery for colorectal cancer, patients who have had a renal and hepatic failure, inability to consume food orally, psychiatric disorders, pregnancy, uncontrolled infection, and all patients who did not have the criteria for inclusion.

In our database, 142 patients were identified, of which 38 patients were excluded because they did not meet the criteria for inclusion and had incomplete medical documentation and the remaining patients were divided into two groups. The treatment group was formed by 52 probants who accepted the proposal of the treating surgeon and received commercially available nutrition (Nutridrink Compact) at least 21 days before the planned surgical procedure as an addition to a normal rational diet. The patient's cooperation is an important factor in the treatment of enteral nutrition. Many patients poorly tolerate enteral nutrition and refuse to leave their normal diet. This resulted in a control group of patients who formed 52 probants who had rational nourishment as usual, and were verbally guided for nutrition.

Patients received Nutridrink Compact (Nutricia) as an addition to a normal rational diet, it is a high-energy nutritionally complete liquid designed for a dietetic procedure for malnutrition that is related to the disease. The content of Nutridrink is mentioned in Table 1.

The following data were collected: body weight, height, a general state of health, age, gender, family status, degree of education, the onset of disease, number of symptoms, metastasis, co-morbidity.

The course of sampling is an important prerequisite for an objective assessment of the patient´s health. The sampling from the patient was realized once by a qualified nurse. Venous sampling was done in the morning after 8 – 12 hours long fasting. The patient was allowed to drink only a small amount of clear water. The blood sample was taken from the peripheral vein of the upper limb. The skin was disinfected with eighty percent ethanol. The blood was taken into the vacuum test tube, the test tube was filled to the mark and subsequently, the sample was mixed and labeled with the personal data of the patient. The material was transported into the laboratory of the company Medirex. The company Medirex is a holder of a certificate of conducting STN EN ISO 9001:2009 and simultaneously of the needed sampling certifications for individual examinations, namely hematological and biochemical. Subsequently, the result of the examination of the patient was recorded into the patient´s medical record.

Blood count, C-reactive protein, albumin, total proteins, and glycemia were recorded.

Blood was collected minimally one month before the planned operation in both groups. In the treatment group, a high-energy nutritional supplement was added to the patient's rational diet for at least 21 days. Subsequently, blood was collected again just before surgery. The patient's weight was determined at least one month before surgery and the second time just before surgery in both patient groups.

The surgery was performed by one surgeon who specializes in the given disease of the colon by laparotomic and laparoscopic surgical techniques. The anastomosis was end-to-end or side-to-side depending on the location and the decision of the surgeon.

Statistical analysis was performed using Microsoft Excel 2010. Quantitative data are expressed as mean ± standard deviation and compared with the t-test. p-value p <0.05 was considered statistically significant.

Laboratory variables are shown in Table 4. Changes in variables were reported, that means laboratory parameters of haemoglobin, leukocytes, albumin, total proteins, CRP, glycaemia in patients in initial state with enteral nutrition and just prior to surgical procedures, and then compared with the control group.

In patients receiving enteral nutrition, the albumin and total proteins increased, which was statistically significant and there was a decrease in the number of leukocytes and CRP, statistically significant, and also glycemia was adjusted. In the treatment group, the haemoglobin changed from 114.2 to 116.90, p = 0.0168, leukocytes WBC from 8.72 to 7.74, p = 0.0025, albumin S-ALB from 35.42 to 37.48, p = 0.0008, total proteins S-CB from 56.02 to 61.1, p = 0.0002, CRP-C reactive protein from 26.5 to 14.092, p = 0.0007, glycemia S-Glu from 7.3 to 6.87, p = 0.0153. In the control group, the haemoglobin changed from 113.0 to 115.61, p = 0.0097, leukocytes WBC from 8.25 to 7.98, p = 0.0973, albumin S-ALB from 33.15 to 33.57, p = 0.1073, total proteins S-CB from 57.1 to 58.94, p = 0.00108, CRP-C reactive protein from 10.6 to 10.45, p = 0.247, glycaemia S-Glu from 6.31 to 5.85, p = 0.027. In the control group, there was a change in total protein, which was statistically significant.

Postoperative complications within 30 days are listed in Table 5. The number of septic complications was significantly lower in patients in the treatment group with enteral nutrition than in patients in the control group (4% compared to 25%, p = 0.04). There wasn´t a significant difference in the number of total complications between the two groups (21% compared to 29%, p = 0.51).

This study retrospectively examined the association of laboratory parameters, namely albumin, total proteins, leukocytes, CRP, glycemia, and preoperative enteral nutrition in patients who underwent a resection of the colon for malignancies. In our study, we reported adding Nutridrink to patients with the oncological disease for at least 21 days, which increased serum albumin, total proteins, and reduced CRP levels in patients undergoing planned colon resection. This preoperative preparation can be a useful strategy as a preoperative method to improve postoperative forecasts in patients. The systemic score of inflammation and nutrition plays an important role in various cancers in certain situations. The reports have shown that inflammation promotes the invasion of tumors and metastases through the activation of IL-6 and T-lymfocytes (Tokunaga et al., 2017). Our study showed that the addition of Nutridrink to treatment before surgery reduced CRP levels and increased serum albumin of total proteins in patients with colorectal cancer who had undergone a therapeutic resection of the colon. We believe that our result is remarkable because our two groups have been well aligned with respect to the basic demographic parameters, thus reducing confusing variables. The surgical variability was reduced because the surgical procedure was performed by one surgeon in both groups.

There are some limitations to this study. Firstly, our set of patients was small, second, nutrition disorders in cancer patients occur not only by cancer pathologies but also by preoperative chemotherapy or radiotherapy, thirdly, our study was retrospective and was performed on one institution. Nevertheless, it is a study, which in Slovakia is one of few comparing the effect of enteral preoperative nutrition in a patient with colorectal cancer undergoing surgical resection. Serum albumin levels are traditionally used as a biochemical indicator of individual nutritional status before surgery. It is considered to be the exact preoperative prognostic indicator for various surgical performances including cardiac, trauma, and general surgery (Truong et al., 2016). While some believe that low albumin levels indicate malnutrition, others assume that hypoalbuminemia stems from a state of chronic disease, and this a resulting inflammation and is not caused by malnutrition, thereby preventing any beneficial effects of nutritional therapy (Truong et al., 2016). With respect to serum albumin levels, this value gradually decreases between 0.08 and 0.17 g.l^-1 per year with age. In addition, elderly patients are usually complicated by comorbidities that increase inflammatory cytokines, and both loss of appetite and loss of muscle mass directly cause hypoalbuminemia (Tominaga et al. 2019).

However, enteral and parenteral nutrition have been shown to improve the results in undernourished patients undergoing large elective surgical intervention (Braga et al., 2002). The agreement is to stabilize the baseline nutritional status and administer the enteral or parenteral nutrition to the severely hypoalbuminate patients before surgery, even if it requires the delay of surgery. In 2012, Oberhofer et al. (2012) showed an increase in CRP in the early postoperative period after colorectal tract surgery correlated with a significant increase in complication rates (p <0.001), which was consistent with Welsch (Welsch et al., 2007), who showed that CRP values greater than 140 mg.l^-1 on a postoperative day 3 or 4 predicted infectious complications and anastomotic leaks after colorectal surgery. In contrast, preoperative CRP levels did not correlate with the incidence of postoperative complications (Truong et al., 2016). CRP is an acute-phase protein that is synthesized in the liver in response to proinflammatory cytokine signaling, primarily through interleukin-6 and alpha tumor necrosis factor. An important role of CRP is to bind phosphocholine to pathogens as well as to apoptotic or necrotic host cells, which in turn activate the complement system and obtain phagocytes.

Serum CRP increases rapidly in response to tissue damage or infection, but an increase in CRP (generally at low levels) is also seen in chronic inflammatory or neoplastic conditions, a process likely to be mediated by various signaling mechanisms (Crockett et al., 2014). Platt et al. (2012) reported data on WBC, CRP, and albumin concentrations in 454 patients undergoing colorectal cancer surgery, of which 104 developed infectious complications. The results showed that CRP measurements after resection for colorectal carcinoma accurately predict infectious complications including anastomotic leakage.

The average time to onset of infectious complications, including anastomotic leakage, was 6 – 8 days after surgery. Colorectal surgery has traditionally been associated with significant morbidity and prolonged hospital stay. The overall complication rate was reported to be 26 – 35%. In particular, infectious complications are a major cause of morbidity and mortality after colorectal surgery (Sonoda et al., 2015). Albumin is considered a negative protein in the acute phase because its concentration decreases during injury and sepsis. In patients with septic shock, the rate of albumin loss in tissue spaces increases by more than 300%. Hypoalbuminaemia is a risk factor for mortality and postoperative complications. Therefore, nutrition control is an important focus of perioperative management. The magnitude of the systemic inflammatory response during the perioperative period, as indicated by acute-phase proteins – in particular C-reactive protein (CRP) – can help identify the risk of postoperative infectious complications.

A correlation was reported between serum albumin and CRP with gastrointestinal cancer (Feng, Zhao and Chen, 2014).

Anastomosis leakage after rectal surgery is one of the most serious and life-threatening complications and still poses a main clinical problem (Welsch et al., 2007). Up to 50% of patients with anastomotic leakage are asymptomatic, which can be explained by extraperitoneal localization of leakage. Postoperative mortality on anastomotic complications is up to 22% and it is estimated, that it constitutes one-third of all deaths after colorectal surgery (Nesbakken et al., 2005). New recommendations for operations and oncology were published in 2016 and 2017. Nutritional intervention before major surgery in patients with malnutrition should be made for at least 10 – 14 days, even at the cost of defering the operation (at least 7 – 14 days) and this is a strong recommendation. Enteral nutrition is the preferred way of feeding. Parenteral nutrition is recommended only if the patient cannot be fed through the digestive tract (Weimann et al., 2017; Arends et al., 2017). However, enteral and parenteral nutrition has been shown to improve the results in undernourished patients undergoing large elective surgical intervention (Braga et al., 2002). Undoubtedly the use of enteral nutrition reduces the number of perioperative complications and decreases the time spent in the hospital (Heyland et al., 2001). It should be remembered that it is very important to continue the nutritional intervention even after the operation (Klek et al., 2011). For example, Giger-Pabst (Giger-Pabst et al., 2013), found that preoperative peroral supplementation with an immune-enriched diet for 3 days did not improve postoperative outcome in patients with gastrointestinal cancer and meanwhile, no positive effects of immunonutritional support were found in patients on ICU. (Atkinson, Sieffert and Bihari, 1998; Bower et al., 1995). The study, which included 1223 critically ill adults, also showed the deleterious effect of early immunonutritional administration (Heyland et al., 2013). In the past, the originally popular parenteral nutrition was replaced by enteral feeding in the early 1990s. Many experts have supported changes in the nutritional approach, especially because there is a lack of evidence-based data. Few authors dared to express their doubts about the enteral technique, including difficulties in administering the required dose or the occurrence of complications (Braga et al., 1999; Gianotti et al., 2000; Gianotti et al., 2002; Gianotti et al., 1997; Heslin et al., 1997; Klek et al., 2008). The management of malnutrition in patients with metastatic carcinoma belongs to the complex management of illness, so the tolerance and effectiveness of ever more aggressive treatment increases and the life quality of patients improve as well (Gallois et al., 2019).