Effects of acute treatment with a tryptophan-rich protein hydrolysate on plasma amino acids, mood and emotional functioning in older women.

RATIONALE: Effective functioning of the neurotransmitter serotonin is important for optimal cognitive and emotional function. Dietary supplements able to increase availability to the brain of the precursor amino acid, tryptophan (TRP), and thereby enhance serotonin synthesis, can have measurable impact on these psychological processes. OBJECTIVES: This study involves a randomised controlled trial of a TRP-rich egg-white protein hydrolysate (DSM Nutritional Products Ltd., Switzerland) on plasma amino acids, cognition, mood and emotional processing in older women. METHODS: Following a baseline test day without treatment, 60 healthy women aged 45-65 years received drinks containing either 2 or 4 g of TRP-rich protein hydrolysate product or 3.11 g casein hydrolysate as a control. One hour later, they undertook a 2-h battery of cognitive and emotional tests. RESULTS: The TRP-rich protein hydrolysate produced the expected dose-dependent increase in the ratio of plasma TRP to competing large neutral amino acids. TRP-rich protein hydrolysate (2 g only) prevented both the decline in wellbeing and increase in fatigue seen over the test session in the control group. This treatment dose resulted in a significant shift in emotional processing towards positive words and reduced negative bias in assessing negative facial expressions. Effects on cognition were small and not statistically reliable and are not reported here. However, there was no evidence for any adverse effects. CONCLUSIONS: Consumption of a low dose of TRP-rich protein hydrolysate may have beneficial effects on emotional function that could promote feelings of wellbeing, possibly conferring resistance to deterioration in mood in healthy subjects or depressive episodes.

Survival analysis and prognostic nomogram for patients undergoing resection of extrahepatic cholangiocarcinoma.

BACKGROUND: Tumor location of extrahepatic cholangiocarcinoma (CCA) might influence survival after resection. METHODS: A consecutive series of 175 patients who had undergone a potentially curative resection of extrahepatic CCA was analyzed. We calculated concordance indices of different constructed prognostic models for survival including TNM (tumour-node-metastasis) staging and developed a nomogram of the most sensitive model. RESULTS: Overall cancer-specific survival rates were 83%, 58%, and 26% at 1, 2, and 5 years, respectively. Cancer-specific survival according to location was 42% for proximal, 23% for mid, and 19% for distal CCA after 5 years. Tumor location was not an independent significant predictor (P = 0.06). A prognostic model using all potential prognostic variables predicted survival better compared with TNM staging (concordance index 0.65 versus 0.63). A reduced model containing only lymph node status, microscopically residual tumor status, and tumor differentiation grade, also outperformed TNM staging (concordance index 0.66). CONCLUSIONS: Tumor location of extrahepatic CCA does not independently predict cancer-specific survival after resection. We developed a nomogram, based on a prognostic model with lymph node status, microscopically residual tumor status of resection margins, and tumor differentiation grade, that predicted survival better than TNM staging.

Successful pulmonary endarterectomy in a patient with klinefelter syndrome.

Klinefelter syndrome (KS) is a frequent genetic disorder due to one or more supernumerary X chromosomes. KS is associated with an increased risk for venous thromboembolic events like deep venous thrombosis and pulmonary embolism. This paper describes a 37-year-old male patient with KS referred to our tertiary center with chronic thromboembolic pulmonary hypertension, and who was successfully treated by pulmonary endarterectomy.

Effects of low doses of casein hydrolysate on post-challenge glucose and insulin levels.

BACKGROUND: Ingestion of high doses of casein hydrolysate stimulates insulin secretion in healthy subjects and patients with type 2 diabetes. The effects of low doses have not been studied. The aim of this study was to assess the effect of lower doses of a casein hydrolysate on the glucose and insulin responses to an oral glucose tolerance test in patients with type 2 diabetes. METHODS: In this randomized, placebo-controlled, double-blind study, thirteen patients with type 2 diabetes (age: 58±1 years) were studied. Glucose, insulin and C-peptide responses were determined after the oral administration of 0 (control), 6 or 12 g protein hydrolysate in combination with 50 g carbohydrate. RESULTS: Twelve grams of casein hydrolysate, but not 6g, elevated insulin levels and decreased glucose levels post-challenge. These changes over time were not large enough to also affect the total area under the curve of glucose and insulin. C-peptide levels did not change after both treatments. CONCLUSION: Ingestion of six grams of casein hydrolysate did not affect glucose or insulin responses. Intake of 12 g of casein hydrolysate has a small positive effect on post-challenge insulin and glucose levels in patients with type 2 diabetes.

A whey-based glutathione-enhancing diet decreases allergen-induced airway contraction in a guinea-pig model of asthma.

Since an allergen-induced early asthmatic reaction is likely to be accompanied by oxidative stress and since levels of the endogenous antioxidant glutathione can be enhanced by a whey-based diet (undenatured whey protein concentrate, UWPC), it was investigated whether UWPC could alleviate allergen-induced lung contractions. Guinea pigs were fed water or UWPC twice a day starting at day - 3 up to day 20. The animals were sensitised to ovalbumin or received saline on day 0. Serum samples were taken at several days after sensitisation to measure allergen-specific IgG. On day 20, lungs were isolated and perfused with buffer containing the allergen ovalbumin. Airway contractions were assessed, and mediators and indicators for oxidative stress were measured in the lung effluent. Moreover, glutathione levels were determined in the liver. The indicator of oxidative stress and airway contractile mediator, 8-iso-PGF(2α), was increased upon ovalbumin challenge in ovalbumin-sensitised groups. Furthermore, thiobarbituric acid-reactive substances (TBARS) were increased as well. Sensitisation with ovalbumin increased IgG levels from day 12 up to day 20, which were not influenced by the UWPC diet. In contrast, the UWPC diet significantly enhanced glutathione levels in the liver. Moreover, the UWPC diet significantly reduced the ovalbumin-induced anaphylactic response by 45 % and decreased PGE2 levels by 55 % in the effluent fluid. We show for the first time that during anaphylaxis, there is acute oxidative stress in the respiratory tract. The UWPC diet did not influence the sensitisation response to the allergen but did increase endogenous glutathione levels. The UWPC diet profoundly reduces allergen-induced airway constrictions, which opens new avenues for dietary management of allergic diseases.

Multidisciplinary management of hilar cholangiocarcinoma (Klatskin tumor): extended resection is associated with improved survival.

BACKGROUND: Effective diagnosis and treatment of patients with hilar cholangiocarcinoma (HCCA) is based on the synergy of endoscopists, interventional radiologists, radiotherapists and surgeons. This report summarizes the multidisciplinary experience in management of HCCA over a period of two decades at the Academic Medical Center in Amsterdam, with emphasis on surgical outcome. METHODS: From 1988 until 2003, 117 consecutive patients underwent resection on the suspicion of HCCA. Preoperative work-up included staging laparoscopy, preoperative biliary drainage, assessment of volume/function of future remnant liver and radiation therapy to prevent seeding metastases. More aggressive surgical approach combining hilar resection with extended liver resection was applied as of 1998. Outcomes of resection including actuarial 5-year survival were assessed. RESULTS: Eighteen patients (15.3%) appeared to have a benign lesion on microscopical examination of the specimen, leaving 99 patients with histologically proven HCCA. These 99 patients were analysed according to three 5-year time periods of resection, i.e. period 1 (1988-1993, n=45), 2 (1993-1998, n=25) and 3 (1998-2003, n=29). The rate of R0 resections increased and actuarial five-year survival significantly improved from 20±5% for the periods 1 and 2, to 33±9% in period 3 (p<0.05). Postoperative morbidity and mortality in the last period were 68% and 10%, respectively. CONCLUSION: Extended surgical resection resulted in increased rate of R0 resections and significantly improved survival. Candidates for resection should be considered by a specialized, multidisciplinary team.

Mucinous cystadenomas in liver: management and origin.

BACKGROUND: Mucinous cystadenomas of the liver are rare cystic neoplasms. The aim of this study was to assess management of a consecutive series of patients who underwent laparotomy for a suspected cystadenoma or cystadenocarcinoma. Secondly, the origin of ovarian stroma (OS) in mucinous liver cystadenomas was examined during early embryonic development. PATIENTS AND METHODS: Patients diagnosed with mucinous liver cystadenomas or cystadenocarcinoma between 1994 and 2009 were included. Pathology specimens of patients who had undergone resection were reviewed for OS. Furthermore, in human embryos, morphology of the peritoneal epithelium and the position of the gonads in relation to the embryonic liver, pancreas and spleen were examined. RESULTS: 15 surgically treated patients (13 female, 2 male) with hepatic tumors were eventually diagnosed with mucinous liver cystadenomas (12) or cystadenocarcinomas (3). OS was present in all female patients with mucinous cystadenoma or cystadenocarcinoma. The 2 male patients were rediagnosed as intraductal papillary mucinous neoplasm (IPMN) or cystadenocarcinoma with features of IPMN. In human embryos, preceding their 'descent', the gonads are situated directly under the diaphragm, dorsal to the liver, the tail of the pancreas and the spleen, but separated from these organs by the peritoneal cavity. In contrast to the peritoneal epithelium elsewhere, the cells covering the gonads show an activated morphology. CONCLUSION: For the diagnosis of mucinous liver cystadenoma, the presence of OS is prerequisite. This may be explained by the common origin of cystadenoma and OS in epithelial cells that cover the embryonic gonads in early fetal life.

Glutathione prevents the early asthmatic reaction and airway hyperresponsiveness in guinea pigs.

The prevalence of asthma has increased worldwide. The reasons for this rise remain unclear. Oxidative stress plays an important role in the pathogenesis of asthma. Glutathione (GSH) is the major representative of the class of nonprotein thiols and plays a pivotal role in a variety of enzymatic and nonenzymatic reactions that protect tissues against oxidative stress. In antioxidative reactions, GSH is converted into its oxidized form, glutathione disulfide (GSSG) that in its turn is enzymatically reduced into GSH to maintain a physiological redox balance. We used a guinea pig model of asthma to assess whether the early asthmatic reaction is associated with decreased lung levels of glutathione, and whether decreased glutathione is implicated in the increased airway smooth muscle reactivity that is associated with exposure of the lungs to allergen. Lung glutathione levels were decreased immediately after the onset of the early asthmatic reaction in vivo and associated with the release of 8-iso-PGF(2alpha), an indicator for oxidative stress. Glutathione ethylester, a glutathione precursor, blunted the airway obstruction during an early asthmatic reaction in a perfusion model and glutathione depletion rendered the airways hyperreactive. Glutathione ethyl ester in the buffer prevented this hyperreactivity. These results indicate that glutathione can modulate the early asthmatic reaction as well as the airway hyperresponsiveness.

Effect of tryptophan-rich egg protein hydrolysate on brain tryptophan availability, stress and performance.

BACKGROUND & AIMS: Reduced brain serotonin function is involved in stress-related disturbances and may particularly occur under chronic stress. Although serotonin production directly depends on the availability of its plasma dietary amino acid precursor tryptophan (TRP), previously described effects of tryptophan-rich food sources on stress-related behavior are rather modest. Recently, an egg protein hydrolysate (EPH) was developed that showed a much greater effect on brain TRP availability than pure TRP and other TRP-food sources and therefore may be more effective for performance under stress. The aim of the present study was to investigate the effects of EPH compared to placebo protein on plasma amino acids, stress coping and performance in subjects with high and low chronic stress vulnerabilities. METHODS: In a placebo-controlled, double-blind, crossover study, 17 participants with high and 18 participants with low chronic stress vulnerabilities were monitored for mood and performance under acute stress exposure either following intake of EPH or placebo. RESULTS: EPH significantly increased plasma TRP availability for uptake into the brain, decreased depressive mood in all subjects and improved perceptual-motor and vigilance performance only in low chronic stress-vulnerable subjects. CONCLUSIONS: The acute use of a TRP-rich egg protein hydrolysate (EPH) is an adequate method to increase plasma TRP for uptake into the brain and may be beneficial for perceptual-motor and vigilance performance in healthy volunteers.

Preoperative biliary drainage in patients with obstructive jaundice: history and current status.

RATIONALE: Preoperative biliary drainage (PBD) has been introduced to improve outcome after surgery in patients suffering from obstructive jaundice due to a potentially resectable proximal or distal bile duct/pancreatic head lesion. In experimental models, PBD is almost exclusively associated with beneficial results: improved liver function and nutritional status; reduction of systemic endotoxemia; cytokine release; and, as a result, an improved immune response. Mortality was significantly reduced in these animal models. Human studies show conflicting results. FINDINGS: For distal obstruction, currently the "best-evidence" available clearly shows that routine PBD does not yield the appreciated improvement in postoperative morbidity and mortality in patients undergoing resection. Moreover, PBD harbors its own complications. However, most of the available data are outdated or suffer from methodological deficits. CONCLUSION: The highest level of evidence for PBD to be performed in proximal obstruction, as well as over the preferred mode, is lacking but, nevertheless, assimilated in the treatment algorithm for many centers. Logistics and waiting lists, although sometimes inevitable, could be factors that might influence the decision to opt for PBD, as well as an extended diagnostic workup with laparoscopy (on indication) or scheduled preoperative chemotherapy.

Surgery for extrahepatic cholangiocarcinoma: predictors of survival.

The incidence of extrahepatic cholangiocarcinoma is increasing worldwide and is often in an advanced stage at diagnosis and difficult to treat. The TNM (tumor node metastasis) cancer staging system predicts survival on the basis of tumor histopathology and the presence of distant metastases. However, numerous prognostic factors have been described that are not included in the TNM system. This review focuses on the prognostic significance of clinical, surgical, and histopathological factors as reported in the literature. Overall, the most important independent prognostic factors for long-term survival are negative surgical margins, lymph node status, and differentiation grade of the tumor. Further improvement of staging systems and identification of prognostic factors are crucial if we are to better select patients for surgical and adjuvant therapy and, hence, increase the rate of curative resections.

Staging of cholangiocarcinoma: the role of endoscopy.

The main question for staging is resectability, which is reliant on vascular, longitudinal, and metastatic spread. Today, accurate staging of perihilar tumors is achieved by non-invasive diagnostic investigations. Direct cholangiography has been the gold standard as a diagnostic procedure in recent decades. Endoscopic retrograde cholangiopancreaticography (ERCP) often only shows the ducts below the obstruction, and visualization of an obstructed part of the biliary tree is often not possible. Direct cholangiography reveals no information about local tumor extension, lymph nodes, or vascular involvement. Because of the given limitations, potential complications (cholangitis, sepsis) associated with direct cholangiography and reduction of the accuracy of subsequent cross-sectional imaging studies, these invasive techniques should only be used in the case of palliative interventions. Endoscopic ultrasonography-guided fine-needle aspiration (EUS-FNA) can be used to assess the nature of biliary strictures and to derive information about the extent of periductal disease and the presence of lymph node metastases. In a study by Fritscher-Ravens, 44 patients with hilar strictures underwent EUS-FNA. The overall diagnostic accuracy, sensitivity, specificity, positive and negative predictive values were 91% (95% CI, 78.4-96.3%), 89% (95% CI, 73.3-96.8%), 100% (95% CI, 63.1-100%), 100% (95% CI, 88.8-100%), and 67% (95% CI, 34.9-90%), respectively. The planned surgical approach was changed in 27 of 44 patients. In 15-20% of cholangiocarcinoma, patients with unremarkable abdominal imaging studies have metastatic lymph node involvement according to EUS evaluation. Due to the risk of peritoneal seeding, however, EUS with FNA is not recommended in patients still with a potential curative tumor.

Biliary drainage attenuates postischemic reperfusion injury in the cholestatic rat liver.

BACKGROUND: The combination of hepatic ischemia and cholestasis, both identified as risk factors for oxidative stress, potentially enhances postischemic reperfusion (I/R) injury. Preoperative biliary drainage relieves oxidative stress and therefore seems a worthwhile intervention in cholestatic patients undergoing major liver resection. AIM: To assess the effect of biliary decompression on I/R injury in a reversible bile duct ligation (BDL) model in the rat. METHODS: Male Wistar rats were randomized into 3 groups. The first group underwent 30 minutes of partial liver ischemia after 7 days BDL; the second group underwent internal drainage (ID) after 7 days BDL and after 5 days, were subjected to partial liver ischemia. The last group (control animals) underwent 2 sham laparotomies and subsequent ischemia. Inflammatory response (interleukin [IL]-6, IL-10, GRO/KC, and interferon-gamma), hepatic damage and oxidative stress were assessed during 24 hours of reperfusion. RESULTS: Cholestatic rats, as compared with the ID and control groups, showed significantly increased I/R injury as determined by transaminase release, histologic injury score and neutrophil infiltration. Plasma IL-6, IL-10, and GRO/KC (a CXC chemokine) were significantly increased in the BDL group (P < .05 vs control and ID). Moreover, the hepatic antioxidant capacity was strongly decreased in the BDL group (P < .01 vs control and ID). No significant differences for most parameters were seen in the ID group as compared to the control group. CONCLUSION: The cholestatic rat is more susceptible to postischemic liver injury and these injurious effects were significantly attenuated by biliary decompression.

Immunoglobulin G4-related sclerosing cholangitis in patients resected for presumed malignant bile duct strictures.

BACKGROUND: Immunoglobulin (Ig) G(4)-related lymphoplasmacytic sclerosing pancreatitis has been described in the context of autoimmune pancreatitis mimicking distal cholangiocarcinoma. The aim of this study was to assess the occurrence of this entity in benign bile duct strictures in patients resected for presumed hilar cholangiocarcinoma. METHODS: Of 185 patients who had undergone resection of proximal bile ducts on suspicion of hilar cholangiocarcinoma between January 1984 and June 2005, 32 (17.3 per cent) had a benign bile duct stricture on histopathological examination. After re-evaluation, further immunohistochemical analysis was performed on specimens from patients with features of autoimmune-like disease. RESULTS: The periductal stroma in 15 patients showed features of autoimmune-like disease (diffuse, moderate to severe lymphoplasmacytic infiltration with marked fibrosis). Abundant IgG(4)-positive plasma cell infiltration around the bile duct lesions was seen in two of these. Although not significant, patients with features of autoimmune-like disease on histological changes showed a higher incidence of recurrent biliary complications than those without (P = 0.250). CONCLUSION: Features of autoimmune-like bile duct disease were seen in almost half (15 of 32) of patients with benign hilar strictures resected for presumed hilar cholangiocarcinoma. Frank IgG(4)-related sclerosing disease was found in only two of the 15 patients with autoimmune-like bile duct disease.

Topical negative pressure therapy in wounds after cardiothoracic surgery: successful experience supported by literature.

BACKGROUND: Patients undergoing cardiothoracic surgery are at substantial risk of developing surgical site infections (SSI). SSI is not only associated with an increased morbidity but also with high mortality. Topical negative pressure therapy (TNP) is a promising method for treating surgical site defects (SSD). In recent years, we have gained a wide experience with TNP in a great variety of SSD. METHODS: We completed a prospective follow-up report of all patients treated with TNP after cardiothoracic surgery at the Academic Medical Centre Amsterdam, a university hospital. A review of the current evidence for TNP in cardiothoracic surgery is presented. RESULTS: Between August 2000 and March 2005, TNP was used in 105 patients in 113 SSD. As we gained more experience, we saw a decline in hospital stay ( P < 0.0001) and duration of TNP therapy. Surgical closure was performed in 62 % of patients using simple surgical (reconstructive) techniques. Therapy-related complications were rare (n = 1). CONCLUSION: Based on clinical findings and supported by the research presented, the treatment modality of choice for SSD after cardiothoracic surgery is TNP.

Long-term results of boerema anterior gastropexy in children.

OBJECTIVES: To analyze the long-term results of Boerema anterior gastropexy using the Visick grading system in a university teaching hospital. METHODS: Retrospective review of 247 children with severe or complicated gastroesophageal reflux disease (GERD). Patients who underwent primary gastropexy between 1990 and 2001 were divided in 3 groups: (A) neurologic impaired patients (n = 83); (B) esophageal atresia patients (n = 36); and (C) patients without underlying disease (n = 128). The median length of follow-up after gastropexy was 7 years and 8 months (range, 1.5-13 years). Follow-up was carried out using a standardized questionnaire and was obtained by telephone. Postoperative recurrence of symptoms during follow-up was considered as failure of the operation. RESULTS: Postoperative complications occurred in 20 patients (24%) in group A, in 13 patients (36%) in group B and in 23 patients (18%) in group C. Thirty-three patients died during the follow-up period, 5 of whom during the postoperative period. Six children could not be traced; thus, 208 were available for long-term follow-up. Postoperative failures occurred in 12 patients (23%) in group A, in 11 patients (31%) in group B and in 17 patients in group C (14%). Reoperation for recurrence of symptoms due to GERD was performed in 6 patients in group A, in 7 patients in group B and in 2 patients in group C. The final outcome at the time of interview was successful in 81% of group A, in 88% of group B and in 91% of group C. CONCLUSIONS: In the long term, Boerema anterior gastropexy is an effective operation for complicated GERD in children without underlying disease as well as in neurologically impaired children and patients with esophageal atresia.

Risk control of surgical site infection after cardiothoracic surgery.

The purpose of this prospective study was to investigate whether a risk control programme based on risk assessment, new treatment modalities and the presence of a surveillance programme reduces the incidence of surgical site infections (SSI). Between January 2001 and December 2003, 167 patients were treated for a total of 183 SSIs. Data were collected on pre-operative risk factors, intra-operative data and postoperative recovery, including complications, infecting organisms, SSI treatment techniques and length of hospital stay. In this series, the total incidence of SSI was 5.6%. The mean age of affected patients was 65.1 years with a range of 20-87 years. Mean intensive care and hospital stay for SSI was 3.6 days and 18.8 days, respectively. Total mortality was 4.8%. Many risk factors were encountered, some of which were associated with a high morbidity. The majority of SSIs were treated by topical negative pressure therapy (N=81), which gave few side-effects and good clinical results. After starting the surveillance programme, a steady decline in prevalence was observed from 8.9% to 3.9%. This series adds to the evidence that SSI after cardiothoracic surgery is a major but mainly preventable cause of morbidity and mortality. Risk factor assessment, application of novel treatment modalities and an adequate surveillance system all increased patient safety.