Prognostic Impact and Functional Annotations of KIF11 and KIF14 Expression in Patients with Colorectal Cancer.

Genomic instability (GIN) has an important contribution to the pathology of colorectal cancer (CRC). Therefore, we selected mitosis and cytokinesis kinesins, KIF11 and KIF14, as factors of potential clinical and functional value in CRC, as their aberrant expression has been suspected to underlie GIN. We examined the expression and the prognostic and biological significance of KIF11 and KIF14 in CRC via in-house immunohistochemistry on tissue microarrays, public mRNA expression datasets, as well as bioinformatics tools. We found that KIF11 and KIF14 expression, at both the protein and mRNA level, was markedly altered in cancer tissues compared to respective controls, which was reflected in the clinical outcome of CRC patients. Specifically, we provide the first evidence that KIF11 protein and mRNA, KIF14 mRNA, as well as both proteins together, can significantly discriminate between CRC patients with better and worse overall survival independently of other relevant clinical risk factors. The negative prognostic factors for OS were high KIF11 protein, high KIF11 protein + low KIF14 protein, low KIF11 mRNA and low KIF14 mRNA. Functional enrichment analysis revealed that the gene sets related to the cell cycle, DNA replication, DNA repair and recombination, among others, were positively associated with KIF11 or KIF14 expression in CRC tissues. In TCGA cohort, the positive correlations between several measures related to GIN and the expression of KIFs were also demonstrated. In conclusion, our results suggest that CRC patients can be stratified into distinct risk categories by biological and molecular determinants, such as KIF11 and KIF14 expression and, mechanistically, this is likely attributable to their role in maintaining genome integrity.

Body composition among patients undergoing surgery for colorectal cancer.

INTRODUCTION: Nutritional status assessment is an important part of preoperative patient evaluation, but the standard anthropometric parameters do not appear to be adequate. AIM: To determine the changes in the values of bioelectrical impedance analysis (BIA) parameters in patients 3 months after undergoing surgery for colorectal cancer (CRC). MATERIAL AND METHODS: BIA and nutritional status assessment parameters were determined in 80 patients prior to undergoing surgery for CRC. The results 3 months after surgery for 64 of those patients were then compared with their initial assessments. RESULTS: According to standard WHO ranges, 54% of the patients were diagnosed as being overweight and 29% as obese. The percentage of patients categorized as obese amounted to 56% when this was defined as high fat mass. Moderate sarcopaenia, defined as a low skeletal muscle index (SMI) or low percentage of skeletal muscle mass, was diagnosed in 21% and 29% of patients, respectively. Patients with postoperative weakness that made it impossible for them to attend the control visit had a lower preoperative skeletal muscle mass (p = 0.01) and SMI value (p = 0.001). Parameters of BIA did not discriminate patients with postoperative complications, which occurred in 23% of individuals enrolled. CONCLUSIONS: A significant proportion of the patients undergoing surgery for CRC were overweight or obese, which could mask the sarcopaenia that presented in 21-29% of them. Sarcopaenia was the only parameter predictive of a postoperative decrease in performance status.

Circulating Leptin, Adiponectin, and Tumor Necrosis Factor-Alpha in Patients Undergoing Surgery Due to Colorectal Cancer.

BACKGROUND: Adipocytokines have been proposed as factors mediating associations between obesity and inflammation in patients with colorectal cancer (CRC). Thus, the aim of this study was to determine the clinical relationships between blood concentrations of leptin (LEP), adiponectin (ADP), and tumor necrosis factor alpha (TNF-alpha) and the outcomes measured in patients with CRC undergoing surgery. PATIENTS AND METHODS: History, body composition, and blood concentrations of LEP, ADP, and TNF-alpha were determined in 107 patients undergoing surgery due to CRC. The patients were followed up for 619.72 ± 371.65 days. RESULTS: Compared to patients with stage II CRC, individuals with clinical stage I CRC had significantly lower ADP and higher TNF-alpha blood concentrations. We found significant correlations between the clinical stage of CRC (early vs. localized vs. metastatic) and the following: crude blood ADP concentration (R = 0.25; p = 0.015), ADP-to-TNF-alpha ratio (R = 0.31; p = 0.002), and ADP when indexed to body surface area (R = 0.25; p = 0.008) and to fat mass (R = 0.25; p = 0.016). The risk of death during the long-term follow-up period was independently related to the clinical stage of CRC, impairment of the patient's functional status, and higher blood carcinoembryonic antigen concentration. In Kaplan-Meier survival analysis, patients with blood LEP concentrations adjusted to a visceral adipose tissue score of ≥0.47 had a significantly better likelihood of surviving than their counterparts. CONCLUSIONS: In patients with CRC undergoing surgery, blood ADP and TNF-alpha concentrations were associated with the clinical stage of the cancer, likelihood of radical tumor excision, occurrence of nonsurgical postoperative complications, and long-term survival, which suggests the role of dysregulation in the endocrine function of adipose tissue in response to the neoplasmatic process.

Total blood lymphocyte count as a prognostic factor among unselected inpatients.

PURPOSE: The aim of this study was to determine the relationships between total lymphocyte count (TLC) and prognosis among inpatients. PATIENTS AND METHODS: We retrospectively analyzed data from electronic medical documentation of 54 976 inpatients hospitalized in an urban university hospital during 3 consecutive years (2014-2017). RESULTS: TLC was available for 12 651 (23.01%) of the inpatients. Patients with TLC <0.8 G/L constituted about 15% of the inpatients studied and had the highest risk of death, hospital readmission within 14 days, hospital readmission within 30 days and hospital readmission within 1 year, the lowest values for biochemical parameters of nutritional status assessment, and the highest C-reactive protein levels. An increase in TLC was associated with reduced risk of in-hospital death (odds ratio [OR]; 95% confidence interval [CI]): 0.31; 0.27-0.36 and 14-day readmission: 0.78; 0.72-0.86. The risk of in-hospital death associated with the Nutritional Risk Screening 2002 (NRS-2002) score, blood albumin concentration, and the score for the combined values of hemoglobin, TLC, albumin and neutrophils (HLAN) was (OR; 95% CI): 2.44; 2.35-2.53; 0.32; 0.28-0.36; and 0.96; 0.94-0.97; respectively. CONCLUSIONS: TLC < 0.8 G/L is associated with the highest risk of in-hospital death, 14-day and 30-day readmission, and longer in-hospital stay. An increase in TLC predicted in-hospital survival and freedom from early readmission with a power similar to or greater than a number of prognostic formulas based on questionnaires (e.g. NRS-2002), biochemical parameters (e.g. albumin) and formulas composed of multiple parameters (e.g. HLAN).

Blood albumin as a prognostic factor among unselected medically treated inpatients.

Aim: The aim of this study is to determine the prognostic value of blood albumin (BA) in an unselected population of inpatients. Materials & methods: We performed prospective analysis of the medical documentation of 7279 patients hospitalized between July 2014 and September 2017. Results: Individuals with BA ≥3.35 mg/dl had significantly lower risk of in-hospital death (odds ratio [OR]: 0.22; 95% CI: 0.19-0.27; p < 0.001) and 14-day readmission (OR: 0.64; 95% CI: 0.55-0.77; p < 0.0001). BA concentration was the strongest favorable factor predicting inpatient survival in a Cox hazard regression model (OR: 0.43; 95% CI: 0.36-0.50; p < 0.001), did not correlate with body mass index and actual-to-ideal bodyweight ratio and was strongly affected by numerous non-nutrient factors. Conclusion: BA concentration showed similar or better predictive and diagnostic power in relation to all-cause in-hospital mortality and 14-day readmission among inpatients than selected multifactorial scores.

Body mass index as a biomarker for the evaluation of the "Obesity Paradox" among inpatients.

BACKGROUND: Overweight and obesity are, on the one hand, recognized as risk factors for many health-related disorders, and, on the other, as favorable prognostic factors in various patients treated for several different conditions; what is called the "obesity paradox". Until now, the existence of this phenomenon among a general population of consecutive inpatients has not been evaluated. We decided, therefore, to perform an evaluation. PATIENTS AND METHODS: Historical prospective analysis of the medical documentation of 23 603 hospitalizations during two consecutive years in one center was performed. The outcomes measured were as follows: length of stay, in-hospital all-cause mortality, and non-scheduled readmission in the 14-day, 30-day and one-year periods following discharge. RESULTS: Overweight and obese patients had a lower or similar prevalence of the measured outcomes than malnourished patients and those of normal weight. Adjustment of the standard WHO BMI ranges for patients aged ≥65 y (normal weight BMI range 23-33 kg/m2) made these differences more apparent. In logistic regression, the ratio of fat to fat-free body mass was a stronger and unfavorable risk factor compared with BMI for the measured outcomes. CONCLUSIONS: The greatest risk of all-cause in-hospital death and readmission concerned malnourished inpatients. Compared to patients with a normal BMI range, overweight and obesity had a lower or similar (but not greater) risk of the outcomes measured. However, due to several BMI limitations, our observations should be interpreted as suggesting a "BMI paradox", rather than an "obesity paradox".

Characteristics and results of treatment of patients treated surgically with colorectal cancer in old and senile age.

Colorectal cancer (CC) in Poland is the type of cancer with the highest dynamics of disease growth and is epidemiologically related to age. The analysis involved 353 patients operated on due to CC in senile and old age and compared with younger patients. It was found that people at this age are more often diagnosed with CC They were more often women, the patients did not differ in the stage of cancer, while they were significantly more often qualified for surgery due to urgent indications. In patients with colonic cancer, the resectability and radicality of the procedures in comparison with patients with rectal cancer was significantly higher, while there were more complications and deaths in the 30-day follow-up in this group. The overall survival in senile and old age was significantly worse. In the first year of follow-up after surgical treatment of patients in this group, complications and deaths were more frequently observed. However, in patients who survived 12 months after the operation, the overall survival rate did not significantly differ.

The "cholesterol paradox" among inpatients - retrospective analysis of medical documentation.

INTRODUCTION: There is evidence of positive relationships between cholesterol concentration and risk of cardiovascular diseases. However, higher mortality in patients with a low cholesterol level has been reported (the "cholesterol paradox"). MATERIAL AND METHODS: Medical records of 34 191 inpatients between 2014 and 2016 were reviewed and the relationships between total (TC), low-density lipoprotein (LDL-C) and high-density lipoprotein (HDL-C) cholesterol and triglyceride blood concentrations and all-cause in-hospital death and readmission within 14 and 30 days and 1 year were determined in univariate and multivariate analyses. RESULTS: Patients with TC in the lower quartile and LDL-C < 70 mg/dl had greater risk of the outcomes measured than individuals with a TC level in the remaining quartiles and LDL-C ≥ 70 mg/dl. Moreover, patients with TC in the highest quartile, OR (95% CI): 0.36 (0.13-0.99), p < 0.05, and LDL-C ≥ 115 mg/dl, OR (95% CI): 0.53 (0.37-0.77), p < 0.05, had the lowest all-cause in-hospital mortality. However, multivariate analysis using logistic regression and a Cox proportional hazard model showed no significant influence of blood lipid levels on the occurrence of the outcomes measured. CONCLUSIONS: A significant effect of a "cholesterol paradox" linking better prognosis with higher blood lipid concentration was found only in univariate analysis but, after adjustment for clinical characteristics in multivariate analysis, the plasma lipid level had a neutral influence on the occurrence of the measured outcomes. This suggests that a low cholesterol level should be interpreted as a biomarker of illness severity.

Surgical site infection among patients after colorectal cancer surgery.

Wstep: Zakazenie miejsca operowanego wystepuje u 2,5-22,3% operowanych chorych. Jest ono wykladnikiem jakosci leczenia na oddzialach zabiegowych i ma duzy wplyw na jego koszt. Material i metodyka: Analizie poddano chorych, u których w obserwacji 30-dniowej wystapilo zakazenie miejsca operowanego. Grupe wyjsciowa stanowilo 1581 chorych z rozpoznaniem raka jelita grubego poddanych zabiegowi operacyjnemu w jednym osrodku. Kryteriami wylaczajacymi z badania byly: brak wiarygodnej dokumentacji leczenia (szpitalnego lub ambulatoryjnego) i zgon chorego przed 30. dniem po operacji bez rozpoznanego zakazenia miejsca operowanego. Analize statystyczna wykonano przy uzyciu programu Statistica 10. Wyniki: Powiklania pooperacyjne wystapily u 262 chorych (16,6%). Najczesciej wystepujacym bylo zakazenie miejsca operowanego (198 pacjentów; 12,52%). Stwierdzono, ze wystapienie tego powiklania zalezne bylo od zaawansowania klinicznego raka, wieku chorych, chorób wspóltowarzyszacych (cukrzyca i choroby kardiologiczne). Ponadto zauwazono, ze powiklanie to wystepowalo znamiennie czesciej u chorych operowanych w trybie pilnym z powodu powiklan oraz u tych, u których wyloniono stomie jelitowa. Nie stwierdzono natomiast zaleznosci wystapienia tego powiklania od plci chorych i lokalizacji guza nowotworowego. Wniosek: U chorych po operacji raka jelita grubego najwieksze zagrozenie wystapienia zakazenia miejsca operowanego wystapilo u chorych po 75. roku zycia, obciazonych cukrzyca i chorobami kardiologicznymi, z duzym zaawansowaniem klinicznym raka, operowanych w trybie ostrego dyzuru, u których konieczne bylo wylonienie stomii jelitowej (a szczególnie kolostomii).

The fecal occult blood test as a tool for improved outpatient qualification for colonoscopy. A single-center experience and 10-year follow-up survey.

PURPOSE: Colonoscopy is not widely and easily available in all countries, even for symptomatic patients. This is one of the causes of tumors not being diagnosed until an advanced stage. The aim of this study was to estimate the efficacy of the fecal occult blood test (FOBT) in the diagnostic work-up of outpatients referred to a colorectal unit due to indistinct abdominal symptoms. PATIENTS/METHODS: Among 10418 consecutive symptomatic individuals referred to the outpatient clinic, an immunochemical FOBT (Hem-Check 1®) was recommended for 9432 patients with indistinct symptoms as a tool for qualifying them for colonoscopy. All the subjects were treated according to their diagnosis and followed-up for the next 10 years. RESULTS: Colorectal cancer (CRC) was diagnosed in 535 individuals: 393/986 (39.9%) among patients with red-flag symptoms, and 142/951 (14.9%) of individuals with indistinct symptoms and a positive FOBT. In the latter group, less-advanced tumors, classed as such using Dukes' classification, were twice as common and more advanced CRC occurred twice as seldom than in the former. Cancer recurrence-free and overall survival periods after surgical treatment for CRC were significantly longer in patients with indistinct symptoms who qualified for diagnostic procedures on the basis of a positive FOBT. CONCLUSIONS: Patients with symptoms suggesting organic colon disease had a worse prognosis compared to individuals with non-specific symptoms. If bowel endoscopy is not widely and easily available, qualification for colonoscopy on the basis of alarm symptoms and a positive FOBT seems to be an effective strategy in early CRC diagnosis.

Scores of nutritional risk and parameters of nutritional status assessment as predictors of in-hospital mortality and readmissions in the general hospital population.

BACKGROUND & AIMS: We have no "gold standard" for the diagnosis of malnutrition. The aim of this study was to determine the importance of many of the parameters used in nutritional status screening and assessment among inpatients for the prediction of in-hospital mortality, readmission and length of hospitalization. METHODS: On the base of the medical documentation a retrospective analysis was performed of nutritional status screening and assessment parameters for all 20,237 non-selected, consecutive hospitalizations in 15,013 patients over 18 years of age treated in one hospital during the course of one year. RESULTS: The risk of malnutrition expressed as a Nutritional Risk Screening (NRS)-2002 score ≥ 3 concerned 6.4% hospitalizations. The greater risk of in-hospital death, as well as readmission within 14 days and 30 days, was related to an NRS-2002 score ≥3, age >65 years, male gender, urgent admission, body mass deficit calculated as the difference between actual body mass and ideal weight determined according to the Lorentz formula, higher degree of Instant Nutritional Assessment (INA), greater value of a C-reactive protein (CRP)/albumin ratio, and plasma glucose concentration. Whereas, greater blood concentration of albumin, hemoglobin, cholesterol and triglycerides, as well as a greater blood lymphocyte count, were associated with reduced risk of the measured outcomes. CONCLUSIONS: NRS-2002 score, blood albumin, CRP/albumin ratio, and INA seem to be good predictors of in-hospital mortality, readmission rate and length of hospital stay.

Intestinal stoma in patients with colorectal cancer from the perspective of 20-year period of clinical observation.

INTRODUCTION: Intestinal stoma is a procedure most often performed in patients with colorectal cancer. AIM: To identify the percentage of patients with colorectal cancer in which the intestinal stoma was performed. MATERIAL AND METHODS: We retrospectively analysed 443 patients treated during a 20-year period (1994-2013) due to colorectal cancer, in which the intestinal stoma was made during the first surgical intervention. RESULTS: In the second analysed decade, a significant decrease in the percentage of created stomas, definitive stomas in particular, was observed. Stomas were made significantly more often in patients with a tumour located in the rectum, the left half of the colon, and in patients undergoing urgent surgeries. An increased incidence of intestinal stomas was associated with a higher severity of illness and higher proportion of unresectable and non-radical procedures. The definitive stomas were significantly more often made in men and in patients with tumours located in the rectum, whereas temporary stomas were created significantly more often in patients undergoing urgent operations. CONCLUSIONS: In the last decade (2004-2013) the number of intestinal stomas in patients operated due to colorectal cancer was significantly reduced.

Colorectal cancer with intestinal perforation - a retrospective analysis of treatment outcomes.

AIM OF THE STUDY: Colorectal cancer (CRC) is one of the leading cause of death in European population. It progresses without any symptoms in the early stages or those clinical symptoms are very discrete. The aim of this study was a retrospective analysis of treatment outcomes in patients with colorectal cancer complicated with intestinal perforation. MATERIAL AND METHODS: A retrospective analysis of patients urgently operated upon in our Division of General Surgery, because of large intestine perforation, from February 1993 to February 2013 has been made. Results were compared with a group of patients undergoing the elective surgery for colorectal cancer in the same time and Division. RESULTS: Intestinal perforation occurred more often in males (6.52% vs. 6.03%), patients with mucous component in histopathological examination (9.09% vs. 6.01%) and with clinicaly advanced CRC. Patients treated because of perforation had a five-fold higher 30 day mortality rate (9.09% vs. 1.83%), however long-term survival did not differ significantly in both groups. After resectional surgery in 874 patients an intestinal anastomosis was made. Anastomotic leakage was present in 23 (2.6%) patients. This complication occurred six-fold more frequently in a group of patients operated upon because of intestinal perforation (12.20% vs. 2.16%). CONCLUSIONS: In patients with CRC complicated with perforation of the colon in a 30-day observation significantly higher rate of complications and mortality was shown, whereas there was no difference in distant survival rates.

Usefulness of CEA concentration measurement and classic colonoscopy in follow-up after radical treatment of colorectal cancer.

UNLABELLED: There is always a certain rate of recurrence after radical treatment for cancer and to get on it an early detection of disease set back is crucial. MATERIAL AND METHODS: Medical data of patients operated on for primarily detected colorectal cancer in years 1993-2002 was retrospectively reviewed. Usefulness of follow-up means such as physical examination, or CEA and endoscopic surveillance was analyzed. All mentioned above were applied to scheduled follow-up (in 3, 6 and 12 month intervals following an operation and annually after that by the year 5). RESULTS: Complete and reliable data was obtained from 340 out of 502 follow-up intended subjects (67.7%). Elevated CEA was the most frequent predictor of recurrence within non-symptomatic subjects meeting follow-up appointments (60%). The cancer set back diagnosed by means of either physical or endoscopic examinations was the case only in one out of five patients (20.75% and 18.87% respectively). Clinical onset of recurrence making patients meet an unscheduled appointment was found increasing relative risk of nothing-but-palliative option either for them with local set back, or meta-static spread. Relative risk of onset of meta-chronous colonic cancer was significantly higher in patients being affected by synchronous advanced adenoma at time of surgery compared to those with one-fold changes. CONCLUSIONS: CEA scheduled follow-up after treatment for colorectal cancer CRC seems adequate to provide a good outcome of treatment for recurrent tumors. CRC patients presenting with synchronous advanced adenomas at time of surgery are probably to be under more intensive endoscopic surveillance.

[Evaluation of usefulness of faecal occult blood test. Prospective screening study in patients with colorectal neoplasia]. / Ocena przydatnosci pomiaru testu na krew utajona w kale. Prospektywne badanie przesiewowe u chorych na nowotwory jelita grubego.

UNLABELLED: High incidence of colorectal cancer (CRC), good treatment outcome in case of surgery performed at an early stage of the disease, and a simple, low cost and quick diagnostic test, encourage the common use of screening for CRC. The aim of the study was to examine the efficacy of immunochromatographic faecal occult blood (FOB) testing in screening for early colorectal cancer. MATERIAL AND METHODS: A total of 346 subjects with abdominal symptoms of unclear etiology were included to the study. Patients with diagnosed CRC, clinical symptoms suggesting CRC or those with family history of CRC were excluded from the study. All subjects had FOB testing done. All were subjected to sigmoidoscopy, no matter what the result of the screening test was. The sensitivity and specificity of the screening test for CRC was evaluated. RESULTS: The total of 342 subjects aged 29-68 years (median 59 yrs), including 189 (58%) females and 153 (42%) males, were eventually qualified for the study. Colorectal pathology was found in 117 subjects (34.6%). Out of 62 patients with positive tests, 55 (89%) had a colorectal disorder diagnosed during sigmoidoscopy. The results were false positive in 7 cases. Colorectal neoplasia was recognized in 33 cases. These were neoplastic polyps (23) and adenocarcinoma (10). The great majority of neoplastic conditions were found in FOB positive subjects. The sensitivity of the test was 90%, while its specificity reached 84%. Diagnostic accuracy was 84%. Positive and negative predictive values were 15% and 99% respectively. CONCLUSIONS: FOB testing appears highly sensitive and specific for colorectal cancer in patients with unclear abdominal symptoms.