A previous study has shown that malnourished, clinically stable patients with liver cirrhosis are in protein and energy balance at their spontaneous dietary intake and that an improvement in nutritional status cannot be anticipated at this intake (Nielsen et al. 1993). In the present study we examined to what extent oral intake could be increased by nutritional support, and to what extent dietary protein would be retained with increased intake. The techniques used for balance studies were also validated since this information is not available for patients with liver cirrhosis. Fifteen malnourished patients with alcoholic liver cirrhosis were given increasing amounts of a balanced ordinary diet for 38 (SE 3) d. Intakes of protein and energy were recorded by weighing servings and leftovers on food trays. Protein intake was calculated from food tables. Total N disposal was calculated after measurement of urinary N excretion, and protein balance was calculated from the N balance. A validation study of protein balance in a subgroup of patients (analysis of N in food by the duplicate portion technique, correction for incomplete recovery of urine by measurement of urinary para-aminobenzoic acid (PABA) after administration of PABA tablets, and measurement of faecal N) did not change protein balance values. Protein intake increased from 1.0 (SE 01) g/kg per d to 1.8 (SE 0.1) g/kg per d. With increasing protein intake, 84 (SE 8) % of the increase in intake was retained. The rate of protein retention was not saturated at the intakes obtained in this study. Protein intolerance was only encountered in one patient. Available evidence indicates that the requirement for achieving N balance is increased in these patients but protein retention is highly efficient with increased intake. Protein retention is dependent on energy balance. Energy intake was calculated from food tables and total energy expenditure was calculated by the factorial method. A validation study was performed in a subgroup of patients. The energy contents of food sampled by the duplicate portion technique, and of urine and faeces were measured by bomb calorimetry. Resting energy expenditure (REE) was measured by indirect calorimetry before and at the end of the study, and 0, uptake during bicycle exercise was measured before and at the end of the study. The measured intake of metabolizable energy was on average 13% lower than the value given in food tables. Calculated energy expenditure was not changed by the validation study. Mean energy intake was 163 (SE 10) kJ/kg per d and mean energy expenditure was 134 (SE 5 ) kJ/kg per d (P = 0-007), indicating that the protein retention described occurred at a positive energy balance. It is concluded that a substantial retention of dietary protein can be obtained by oral nutrition support over a prolonged period of time in patients with liver cirrhosis. Requirements of protein for maintenance and repletion in these patients are discussed.

Colorectal metastases in the liver grow according to three histological patterns: a pushing pattern, a replacement pattern, and a desmoplastic pattern. The objective of the current study was to explore the prognostic significance of these three growth patterns for survival. The study included 217 consecutive patients, liver resected between 2007 and 2011 due to hepatic metastases from colorectal adenocarcinoma. The growth patterns were assessed on archival hematoxylin and eosin-stained tissue sections. In 150 metastases, the density of the immune cell infiltrate at the tumor periphery was judged by a semi-quantitative method. The prevalence of the pushing-type, the desmoplastic-type, and the replacement-type was 33%, 32%, and 11%, respectively; 24% of the metastases displayed a mixed pattern. Kaplan-Meier analysis and Cox regression demonstrated a prognostic significance of the growth patterns (P ¼ 0.0006, log-rank test), as the replacement pattern appeared as an independent predictor of poor overall survival. For patients with replacement growth, the hazard of death was 2-2.5 times higher than for patients with pushing growth (P ¼ 0.004, cox regression) or mixed growth (P ¼ 0.01), and nearly four times higher than for patients with desmoplastic growth (Po0.0001). The negative prognostic effect of the replacement growth pattern was even more pronounced after adjusting for tumor size. Desmoplastic growth corresponded with small tumor size, dense lymphocytic infiltration and a more favorable prognosis. Eventually, the growth patterns may contribute to a histology-based prognostic biomarker for patients with colorectal liver metastases. Modern Pathology (2014) 27, 1641-1648; doi:10.1038/modpathol.2014.4; published online 23 May 2014Keywords: colorectal cancer; growth pattern; histopathology; liver; metastasis; prognosis; survival During the last 5-10 years, major advances have been made in both the medical and surgical treatment of liver metastases from colorectal carcinoma. The number of patients who undergo liver resection with curative intent has therefore increased significantly. However, so far, little is known on the biological, clinical, and histopathological features that determine prognosis after hepatic resection. The revised and more active treatment strategy has thus fostered a demand for new and better prognostic and predictive markers that can be used for selecting the right treatment regimen for each patient. For primary colorectal cancer, the malignant transformation from adenoma to carcinoma is by now very well described; far less described are the events that govern the progression of metastases in the liver. A greater understanding of the diverse infiltration mechanisms of the metastases, including the intricate interaction with the hepatic microenvironment, might lead to new prognostic and therapeutic prospects.Vermeulen et al 1 identified three histological growth patterns for colorectal liver metastases, suggesting biological differences: (i) a pushing growth pattern, in which the metastasis e...

Nutritional assessment and adequacy of spontaneous dietary intake was evaluated in thirty-seven clinically stable hospitalized patients with alcoholic liver cirrhosis. About two-thirds of the patients had ascites or oedema, or both, and, therefore, body weight could not be used for assessment of nutritional status. Lean body mass (LBM; measured by three consecutive 24 h creatinine excretions) was 62 (range 40-95) % of reference values, mid-arm-muscle area (MAMA) was 70 (range 43-115) % and triceps skinfold (TSF) was 45 (range 20-113)% of reference values (all median values). In patients without ascites or oedema, or both, there was a rectilinear correlation between body weight and LBM and between body weight and MAMA (u 0.93 and 0.85 respectively). In patients with ascites or oedema, or both, the correlation between body weight and LBM was poor as could be expected. We suggest that LBM is a useful measure of nutritional status when body weight is unreliable because of ascites or oedema, or both. Energy balance for the group was calculated from energy intake recorded by a 24 h dietary recall and energy expenditure calculated by the factorial method. Median intake was 102 (range 34-176) % of expenditure. N loss was calculated from the average of three 24 h urea excretions. Protein intake was calculated from the 24 h dietary recall. The N balance was positive in the patients as a group (median intake was 120 (range 26-183) % of output). The most malnourished patients tended to have the most positive N balance which was due to a significantly lower N excretion. The protein requirement for N balance was 0.83 (SE 0.05) g/kg per d and only at an intake above 1.20 g/kg per d were all patients in positive N balance. The median intakes of thiamin, folacin, vitamin D, vitamin E, Mg, and Zn were judged to be insufficient. It is concluded that impaired nutritional status is common among patients with liver cirrhosis, even in a stable clinical condition. It is suggested that nutritional status in these patients is evaluated by dietary recalls, in combination with measurement of body weight in patients without ascites or oedema, or both, or in combination with determination of LBM by three 24 h creatinine excretions in patients with ascites or oedema, or both. Criteria for selection of patients that might benefit from nutritional therapy are discussed.

The aim of the present study was to test the hypothesis that high serum YKL-40 associates with colorectal cancer in subjects at risk of colorectal cancer. We measured serum YKL-40 in a prospective study of 4,496 Danish subjects [2,064 men, 2,432 women, median age 61 years (range, 18-97)] referred to endoscopy due to symptoms or other risk factors for colorectal cancer. Blood samples were collected just before large bowel endoscopy. Serum YKL-40 was determined by ELISA. Serum YKL-40 was higher (P < 0.0001, unadjusted for confounding covariates) in subjects . Multivariable analysis (YKL-40, CEA, age, gender, body mass index, and center) showed that serum YKL-40 was a predictor for colorectal cancer in individuals without comorbidity (OR, 1.25; 95% CI, 1.05-1.40; P ¼ 0.012), whereas this was not the case for those with comorbidity (OR, 0.98; 95% CI, 0.84-1.14; P ¼ 0.80). In conclusion, high serum YKL-40 in subjects suspected of colorectal cancer and without comorbidity associates with colorectal cancer. Determination of serum YKL-40 may be useful in combination with other biomarkers in risk assessment for colorectal cancer. Cancer Epidemiol Biomarkers Prev; 24(3); 621-6. Ó2015 AACR.

Serological biomarkers may be an option for early detection of colorectal cancer (CRC). The present study assessed eight cancer-associated protein biomarkers in plasma from subjects undergoing first time ever colonoscopy due to symptoms attributable to colorectal neoplasia. Plasma AFP, CA19-9, CEA, hs-CRP, CyFra21-1, Ferritin, Galectin-3 and TIMP-1 were determined in EDTA-plasma using the Abbott ARCHITECT® automated immunoassay platform. Primary endpoints were detection of (i) CRC and high-risk adenoma and (ii) CRC. Logistic regression was performed. Final reduced models were constructed selecting the four biomarkers with the highest likelihood scores. Subjects (N = 4,698) were consecutively included during 2010-2012. Colonoscopy detected 512 CRC patients, 319 colonic cancer and 193 rectal cancer. Extra colonic malignancies were detected in 177 patients, 689 had adenomas of which 399 were high-risk, 1,342 had nonneoplastic bowell disease and 1,978 subjects had 'clean' colorectum. Univariable analysis demonstrated that all biomarkers were statistically significant. Multivariate logistic regression demonstrated that the blood-based biomarkers in combination significantly predicted the endpoints. The reduced model resulted in the selection of CEA, hs-CRP, CyFra21-1 and Ferritin for the two endpoints; AUCs were 0.76 and 0.84, respectively. The postive predictive value at 90% sensitivity was 25% for endpoint 1 and the negative predictive value was 93%. For endpoint 2, the postive predictive value was 18% and the negative predictive value was 97%. Combinations of serological protein biomarkers provided a significant identification of subjects with high risk of the presence of colorectal neoplasia. The present set of biomarkers could become important adjunct in early detection of CRC.

Using specific ELISAs, antibody levels of four different isotypes to bovine respiratory syncytial virus (BRSV) were determined in calves, following experimental BRSV infection. Most calves experienced an increase in the specific IgM and IgG1 titres about 6-10 days after infection with BRSV. The IgM titre was transient showing positive titres for only 5-10 days, while specific IgG1 was present for a longer time. IgA was detected concomitantly with IgM but at a lower level. Production of IgG2 anti-BRSV antibodies was detected from 3 weeks after infection. In two closed herds, repeated blood samplings were performed on young stock to analyse maternal immunity. The passively transferred antibodies were mainly of the IgG1 isotype and the half-life of IgG1 to BRSV was estimated to be 26.6 days. One of the herds had an outbreak of enzootic pneumonia, diagnosed to be caused by BRSV. Furthermore, another herd with acute BRSV was followed by weekly blood samples in six calves; in both herds IgM and IgG1 was detected shortly after the appearance of clinical signs. Serum samples from 50 Danish dairy herds (453 samples) were tested for immunoglobulins of the isotypes IgG1, IgG2 and IgM. The presence of antibodies to BRSV was widespread and more than 54% of the samples had BRSV antibodies of both the IgG1 and IgG2 isotypes indicating a high herd prevalence to BRSV. Test samples from two herds out of 50 were free from all isotypes to BRSV.

Patients with cirrhosis of the liver require an increased amount of protein to achieve N balance.However, the utilization of protein with increased protein intake, i.e. the slope from regression analysis of N balance v. intake, is highly efficient (Nielsen ef ul. 1995). In the present study, protein requirement and protein utilization were investigated further by measuring protein synthesis and degradation. In two separate studies, five or six patients with cirrhosis of the liver were refed on a balanced diet for an average of 2 or 4 weeks. Protein and energy intakes were doubled in both studies. Initial and final whole-body protein metabolism was measured in the fed state by primed continous [''Nlglycine infusion. Refeeding caused a statistically significant increase of about 30 % in protein synthesis in both studies while protein degradation was only slightly affected. The increase in protein synthesis was associated with significant increases in plasma concentrations of total amino acids (25 YO), leucine (58 YO), isoleucine (82 YO), valine (72 YO), proline (48 YO) and triiodothyronine (27 YO) while insulin, growth hormone, insulin-like growth factor (1GF)-I and IGF-binding protein-3were not changed significantly. The results indicate that the efficient protein utilization is due to increased protein synthesis, rather than decreased protein degradation, and suggest that increases in plasma amino acids may be responsible for the increased protein synthesis. A comparison of the patients who had a normal protein requirement with the patients who had an increased protein requirement suggests that the increased protein requirement is due to a primary increase in protein degradation. It is speculated that this is due to low levels of IGF-I secondary to impaired liver function, since initial plasma concentration of IGF-I was about 25 YO of control values and remained low during refeeding.Nitrogen retention: Protein metabolism: Alcoholic cirrhosis A large number of patients with liver cirrhosis are malnourished (Lautz et al. 1992) and a review of controlled studies suggested that nutritional therapy improves liver function and may improve the clinical course including mortality (Kondrup et al. 1992). However, the use of artificial nutrition was necessary in all these studies since it is often difficult to increase oral intake sufficiently in patients with cirrhosis. Even in a clinically-stable situation, protein intake is often inadequate among patients with liver cirrhosis, especially since the requirement for protein to achieve N balance is increased (Swart et al. 1989;Nielsen et al. 1993Nielsen et al. , 1995. In contrast, the utilization of protein with increased protein intake (i.e. the slope of balance v. intake) is highly efficient and considered to be similar to that of underweight individuals without organ disease (Nielsen et al. 1995).In order to investigate regulation of protein metabolism during repletion, we performed this study in the fed state before and after refeeding. This was considered necessary bec...

Recently we found one case of endometriosis in the extraperitoneal part of the round ligament (EERL). We found 30 cases previously described in the literature. A comparison showed that 90% were right-sided and often associated with an inguinal hernia. Fertility seemed to be below normal. In four of the cases a laporotomy was done. All had intraperitoneal endometriosis. In cases of EERL and claimed sterility therefore, the presence of intraperitoneal endometriosis should also be considered.