Preoperative oral supplementation with carbohydrate and branched-chain amino acid-enriched nutrient improves insulin resistance in patients undergoing a hepatectomy: a randomized clinical trial using an artificial pancreas

Glucose metabolism is adversely affected in patients following major surgery. Patients may develop hyperglycemia due to a combination of surgical stress and postoperative insulin resistance. A randomized trial was conducted to elucidate the effect of preoperative supplementation with carbohydrates and branched-chain amino acids on postoperative insulin resistance in patients undergoing hepatic resection. A total of 26 patients undergoing a hepatectomy for the treatment of a hepatic neoplasm were randomly assigned to receive a preoperative supplement of carbohydrate and branched-chain amino acid-enriched nutrient mixture or not. The postoperative blood glucose level and the total insulin requirement for normoglycemic control during the 16 h following hepatic resection were determined using the artificial pancreas STG-22. Postoperative insulin requirements for normoglycemic control in the group with preoperative nutritional support was significantly lower than that in the control group (P = 0.039). There was no incidence of hypoglycemia (<40 mg/dL) observed in patients, including those with diabetes mellitus, when the STG-22 was used to control blood glucose levels. STG-22 is a safe and reliable tool to control postoperative glucose metabolism and evaluate insulin resistance. The preoperative oral administration of carbohydrate and branched-chain amino acid-enriched nutrient is of clinical benefit and reduces postoperative insulin resistance in patients undergoing hepatic resection.     

Implementation of a fast-track clinical pathway decreases postoperative length of stay and hospital charges for liver resection

A fast-track clinical pathway is designed to streamline patient care delivery and maximize cost effectiveness. It has decreased postoperative length of stay (LOS) and hospital charges for many surgical procedures. However, data on clinical pathways after liver surgery are sparse. This study examined whether use of a fast-track clinical pathway for patients undergoing elective liver resection affected postoperative LOS and hospital charges. A fast-track clinical pathway was developed and implemented by a multidisciplinary team for patients undergoing liver resection. Between July, 2007 and May, 2008, a total of 117 patients underwent elective liver resection: the fast-track clinical pathway (education of patients and families, earlier oral feeding, earlier discontinuation of intravenous fluid, no drains or nasogastric tubes, early ambulation, use of a urinary catheter for less than 24 h and planned discharge 6 days after surgery) was studied prospectively in 56 patients (postpathway group). These patients were compared with the remainder who had usual care (prepathway group). Outcome measures were postoperative LOS, perioperative hospital charges, intraoperative and postoperative complications, mortality, and readmission rate. Among all patients, 69 (59%) had complicating diseases and/or a history of surgery and 24 patients belonged to American Society of Anesthesiologists grade III–IV. Compared with the prepathway group, the postpathway group had a significantly shorter postoperative LOS (7 vs. 11 days, P < 0.01). The average perioperative hospital charges were RMB 26,626 for patients in the prepathway group and only RMB 21,004 for those in the postpathway group (P < 0.05), with no differences in intraoperative and postoperative complications (P = 0.814), mortality (P = 0.606), and readmission rate (P = 0.424). Implementation of the fast-track clinical pathway is an effective and safe method for reducing postoperative LOS and hospital charges for high-risk patients undergoing elective liver resection. The result supports the further development of fast-track clinical pathways for liver surgical procedures.     

Comparison of escitalopram alone and combined with zolpidem in treating major depression and related sleep impairments

Escitalopram has been shown to be effective for treating major depression (MDD); however, research is lacking regarding its effect on treating MDD-related sleep impairments. The purpose of this study was to assess the efficacy of escitalopram monotherapy and investigate changes in insomnia, depressive symptoms, and quality of life (QOL). Participants were 14 patients with MDD who enrolled in a clinical trial at Jikei University Katsushika Medical Center. Escitalopram monotherapy was used, and hypnotics were administered three times per week for individuals suffering from sleep impairments. The following variables were assessed: (1) sleep quality [Pittsburgh sleep quality index (PSQI)], (2) depression [Zung self-rating depression scale (ZSRDS)], and (3) quality of life (QOL) as determined by the Sheehan disability scale (SDISS) and short form (36) health survey (SF-36). These assessments were conducted prior to any treatment (pre-test) and again 8–12 weeks after treatment (post-test). Monotherapy (E = escitalopram alone; n = 6) and combination therapy (E+ = escitalopram + zolpidem; n = 8) groups were compared. All participants completed the full protocol (average 9.4 ± 1.8 weeks). Regardless of treatment group, participants improved on all assessments (including sleep impairment). However, groups did not differ in their level of improvement. A two-factor ANOVA revealed that the E+ group showed particular improvements in QOL. In treating MDD and associated sleep impairments, zolpidem did not confer additional benefits. Thus, clinicians should consider E monotherapy for patients with MDD-related sleep impairments before prescribing combination therapies.

     

Effects of Multivitamin/Mineral Supplementation on Trace Element Levels in Serum and Follicular Fluid of Women Undergoing in Vitro Fertilization (IVF)

We investigated effects of multivitamin/mineral supplementation on element levels in serum and follicular fluid of women undergoing IVF. We used three groups in this study. The first group was used as an age-matched and nonpregnant control (n = 13). Group 2 (n = 30) constituted the IVF group and women in the third group who were undergoing IVF also received a multivitamin/mineral tablet daily for 45 days. Follicular fluid and serum selenium and zinc levels and follicular fluid copper levels were lower in IVF patients than in controls although follicular fluid aluminum and iron levels were higher in IVF patients than in controls. However, follicular fluid and serum aluminum, copper, zinc and selenium levels, and serum magnesium levels were higher in the multivitamin/mineral group than in the IVF group although follicular fluid iron levels were lower in the multivitamin/mineral group than in the IVF group. In conclusion, we observed that copper, zinc, and selenium in serum and follicular fluid decreased in women undergoing IVF. Multivitamin/mineral supplementation in serum and follicular fluid of women undergoing IVF normalized the trace element levels.     

Effects of different branched-chain amino acids supplementation protocols on the inflammatory response of LPS-stimulated RAW 264.7 macrophages

Although branched-chain amino acids (BCAA) are commonly used as a strategy to recover nutritional status of critically ill patients, recent findings on their role as immunonutrients have been associated with unfavorable outcomes, especially in obese patients. The present study aimed to explore the effects of different BCAA supplementation protocols in the inflammatory response of LPS-stimulated RAW 264.7 macrophages. Cell cultures were divided into five groups, with and without BCAA supplementation, (2 mmol/L of each amino acid). Then, cell cultures followed three different treatment protocols, consisting of a pretreatment (PT), an acute treatment (AT), and a chronic treatment (CT) with BCAA and LPS stimulation (1 µg/mL). Cell viability was analyzed by MTT assay, NO production was assessed by the Griess reaction and IL-6, IL-10, TNF-α and PGE2 synthesis, was evaluated by ELISA. BCAA significantly increased cell viability in AT and CT protocols, and NO and IL-10 synthesis in all treatment protocols. IL-6 synthesis was only increased in PT and CT protocols. TNF-α and PGE2 synthesis were not altered in any of the protocols and groups. BCAA supplementation was able to increase both pro and anti-inflammatory mediators synthesis by RAW 264.7 macrophages, which was influenced by the protocol applied. Moreover, these parameters were significantly increased by isoleucine supplementation, highlighting a potential research field for future studies.

     

Effect of Autogenic Training on General Improvement in Patients with Irritable Bowel Syndrome: A Randomized Controlled Trial

Autogenic training (AT) is a useful and comprehensive relaxation technique. However, no studies have investigated the effects of AT on irritable bowel syndrome (IBS). In this study we tested the hypothesis that AT improves symptoms of IBS. Twenty-one patients with IBS were randomly assigned to AT (n = 11, 5 male, 6 female) or control therapy (n = 10, 5 male, 5 female). AT patients were trained intensively, while the control therapy consisted of discussions about patients’ meal habits and life styles. All patients answered a question related to adequate relief (AR) of IBS symptoms and four questionnaires: Self-induced IBS Questionnaire (SIBSQ), Self-reported Depression Scale (SDS), State-Trait Anxiety Inventory (STAI), and Medical Outcome Short Form 36 Health Survey (SF-36). The proportion of AR in the last AT session in the AT group (9/11, 81.8%) was significantly higher than that in the controls (3/10, 30.0%, Chi-square test, p = 0.048). Two subscales of the SF-36, i.e., social functioning and bodily pain, were significantly improved in the AT group (p < 0.05) as compared to the control group. Role emotional (p = 0.051) and general health (p = 0.068) showed a tendency for improvement in the AT group. AT may be useful in the treatment of IBS by enhancing self-control.     

Surgeons and Patients Disagree on the Potential Consequences of Hypoparathyroidism

ObjectiveTo test the hypothesis that surgeons and their patients underestimate the potential negative impact that permanent hypoparathyroidism has on quality of life (QOL).MethodsWe used a modified SF-36 assessment tool to compare the perceptions of patients with permanent hypoparathyroidism to the perceptions of control subjects who were given a standardized preoperative statement about the complications of hypoparathyroidism. We also elicited the perceptions of endocrine surgeons regarding the QOL impacts of hypoparathyroidism using a subset of questions from the modified SF-36.ResultsA total of 340 postsurgical patients with permanent hypoparathyroidism, 200 controls, and 102 surgeons participated in the study. Both surgeons and controls underestimated the negative impact of hypoparathyroidism on QOL when compared to patients living with permanent hypoparathyroidism. Forty-seven percent of hypoparathyroid patients believed that their health was “much worse” than before surgery, compared with 16% of surgeons (P < .001) and 7% of controls (P < .001). Postoperative hypoparathyroid patients also reported far more negative effects on QOL, from interference with social activities, paresthesias, muscle cramping, and medications than were anticipated by surgeons or controls (P < .05 for all comparisons). In each of the 8 dimensions of QOL, including physical functioning, role limitations due to physical health, role limitations due to emotional problems, energy/fatigue, emotional well-being, social functioning, pain, and general health, hypoparathyroid patients reported a significantly lower mean score compared to the control group (P < .001 for all comparisons).ConclusionThe impact of postoperative hypoparathyroidism on patient QOL is consistently and significantly underestimated by surgeons and subjects receiving surgical consultation. (Endocr Pract. 2014;20:427-446)     

Is the hepatic metabolism of glucose and linoleic acid influenced by species in overfed ducks?

There are genetic differences in the hepatic glucose and linoleic acid metabolisms between Muscovy and Pekin ducks ad libitum-fed. To understand the effect of overfeeding on the hepatic metabolisms in these two species of ducks, we compared the different pathways of glucose and linoleic acid reaching the liver of Muscovy (Cairina moschata) (n = 6) and Pekin (Anas platyrhynchos) (n = 6) ducks overfed for 1 week and sacrificed 2–4 h after their last meal by using the ex vivo method of liver slices incubated for 16 h with [U-¹⁴C]-glucose, [1-¹⁴C]-linoleic acid and [³⁵S]-methionine added to the survival medium. The glucose was the main precursor of triacylglycerol synthesis in the liver of these two species and its hepatic metabolism was similar between species. The hepatic uptake of linoleic acid was 1.7-fold higher (P = 0.020) in the Muscovy duck than in the Pekin duck leading to a 1.9-fold higher (P = 0.017) esterification of this fatty acid in the liver of the Muscovy duck than in that of the Pekin duck. Finally, both species after 1 week of overfeeding exhibited the same capacity to secrete VLDL remaining insufficient to avoid hepatic steatosis.     

Branched‐chain amino acids prevent insulin‐induced hepatic tumor cell proliferation by inducing apoptosis through mTORC1 and mTORC2‐dependent mechanisms

Branched‐chain amino acids (BCAA) supplementation has been reported to suppress the incidence of liver cancer in obese patients with liver cirrhosis or in obese and diabetic model animals of carcinogenesis. Whether BCAA directly suppresses cell proliferation of hepatic tumor cells under hyperinsulinemic condition remain to be defined. The aim of this study was to investigate the effects of BCAA on insulin‐induced proliferation of hepatic tumor cells and determine the underlying mechanisms. BCAA suppressed insulin‐induced cell proliferation of H4IIE, HepG2 cells. In H4IIE cells, BCAA did not affect cell cycle progression but increased apoptosis by suppressing expressions of anti‐apoptotic genes and inducing pro‐apoptotic gene via inactivation of PI3K/Akt and NF‐κB signaling pathways. Further studies demonstrated that BCAA inhibited PI3K/Akt pathway not only by promoting negative feedback loop from mammalian target of rapamycin complex 1 (mTORC1)/S6K1 to PI3K/Akt pathway, but also by suppressing mTORC2 kinase activity toward Akt. Our findings suggest that BCAA supplementation may be useful to suppress liver cancer progression by inhibiting insulin‐induced PI3K/Akt and subsequent anti‐apoptotic pathway, indicating the importance of BCAA supplementation to the obese patients with advanced liver disease. J. Cell. Physiol. 227: 2097–2105, 2012. © 2011 Wiley Periodicals, Inc.     

Intraoperative Hyperglycemia during Liver Resection: Predictors and Association with the Extent of Hepatocytes Injury

Background

Patients undergoing liver resection are at risk for intraoperative hyperglycemia and acute hyperglycemia is known to induce hepatocytes injury. Thus, we aimed to evaluate whether intraoperative hyperglycemia during liver resection is associated with the extent of hepatic injury.

Methods

This 1 year retrospective observation consecutively enrolled 85 patients undergoing liver resection for hepatocellular carcinoma. Blood glucose concentrations were measured at predetermined time points including every start/end of intermittent hepatic inflow occlusion (IHIO) via arterial blood analysis. Postoperative transaminase concentrations were used as surrogate parameters indicating the extent of surgery-related acute hepatocytes injury.

Results

Thirty (35.5%) patients developed hyperglycemia (blood glucose > 180 mg/dl) during surgery. Prolonged (≥ 3 rounds) IHIO (odds ratio [OR] 7.34, P = 0.004) was determined as a risk factors for hyperglycemia as well as cirrhosis (OR 4.07, P = 0.022), lower prothrombin time (OR 0.01, P = 0.025), and greater total cholesterol level (OR 1.04, P = 0.003). Hyperglycemia was independently associated with perioperative increase in transaminase concentrations (aspartate transaminase, β 105.1, standard error 41.7, P = 0.014; alanine transaminase, β 81.6, standard error 38.1, P = 0.035). Of note, blood glucose > 160 or 140 mg/dl was not associated with postoperative transaminase concentrations.

Conclusions

Hyperglycemia during liver resection might be associated with the extent of hepatocytes injury. It would be rational to maintain blood glucose concentration < 180 mg/dl throughout the surgery in consideration of parenchymal disease, coagulation status, lipid profile, and the cumulative hepatic ischemia in patients undergoing liver resection for hepatocellular carcinoma.     

Comparison of Preoperative Alpha-blockade for Resection of Paraganglioma and Pheochromocytoma

ObjectivePhenoxybenzamine (nonselective, noncompetitive alpha-blocker) is the preferred drug for preoperative treatment of pheochromocytoma, but doxazosin (selective, competitive alpha-blocker) may be equally effective. We compared the efficacy of doxazosin vs phenoxybenzamine.MethodsWe conducted a prospective study of patients undergoing pheochromocytoma or paraganglioma resection by randomizing pretreatment with phenoxybenzamine or doxazosin at a single tertiary referral center. The high cost of phenoxybenzamine led to high crossover to doxazosin. Randomization was halted, and a consecutive historical cohort of phenoxybenzamine patients was included for a case-control study design. The efficacy of alpha-blockade was assessed with preinduction infusion of incremental doses of phenylephrine. The primary outcomes were mortality, cardiovascular complications, and intensive care unit admission. The secondary outcomes were hemodynamic instability index (proportion of operation outside of hemodynamic goals), adequacy of blockade by the phenylephrine titration test, and drug costs.ResultsTwenty-four patients were prospectively enrolled (doxazosin, n = 20; phenoxybenzamine, n = 4), and 15 historical patients treated with phenoxybenzamine were added (total phenoxybenzamine, n = 19). No major cardiovascular complications occurred in either group. The phenylephrine dose-response curves showed less blood pressure rise in the phenoxybenzamine than in the doxazosin group (linear regression coefficient = 0.008 vs 0.018, P = .01), suggesting better alpha-blockade in the phenoxybenzamine group. The median hemodynamic instability index was 14% vs 13% in the phenoxybenzamine and doxazosin groups, respectively (P = .56). The median highest daily cost of phenoxybenzamine was $442.20 compared to $5.06 for doxazosin.ConclusionPhenoxybenzamine may blunt intraoperative hypertension better than doxazosin, but this difference did not translate to fewer cardiovascular complications and is offset by a considerably increased cost.     

Effect of leucine supplementation on indices of muscle damage following drop jumps and resistance exercise

The purpose of this study was to determine the effect of leucine supplementation on indices of muscle damage following eccentric-based resistance exercise. In vitro, the amino acid leucine has been shown to reduce proteolysis and stimulate protein synthesis. Twenty-seven untrained males (height 178.6 ± 5.5 cm; body mass 77.7 ± 13.5 kg; age 21.3 ± 1.6 years) were randomly divided into three groups; leucine (L) (n = 10), placebo (P) (n = 9) and control (C) (n = 8). The two experimental groups (L and P) performed 100 depth jumps from 60 cm and six sets of ten repetitions of eccentric-only leg presses. Either leucine (250 mg/kg bm) or placebo was ingested 30 min before, during and immediately post-exercise and the morning of each recovery day following exercise. Muscle function was determined by peak force during an isometric squat and by jump height during a static jump at pre-exercise (PRE) and 24, 48, 72, and 96 h post-exercise (24, 48, 72, 96 h). Additionally, at these time points each group’s serum levels of creatine kinase (CK) and myoglobin (Mb) along with perceived feelings of muscle soreness were determined. None of the C group dependent variables was altered by the recurring testing procedures. Peak force was significantly decreased across all time points for both experimental groups. The L group experienced an attenuated drop in mean peak force across all post-exercise time points compared to the P group. Jump height significantly decreased from PRE for both the L and P group at 24 h and 48 h. CK and Mb was significantly elevated from PRE for both experimental groups at 24 h. Muscle soreness increased across all time points for the both the L and P group, and the L group experienced a significantly higher increase in mean muscle soreness post-exercise. Following exercise-induced muscle damage, high-dose leucine supplementation may help maintain force output during isometric contractions, however, not force output required for complex physical tasks thereby possibly limiting its ergogenic effectiveness.     

Deficiency in Thrombopoietin Induction after Liver Surgery Is Associated with Postoperative Liver Dysfunction

Background and Aims

Thrombopoietin (TPO) has been implicated in the process of liver regeneration and was found to correlate with hepatic function in patients with liver disease. With this investigation we aimed to determine if perioperative TPO levels were associated with postoperative outcome in patients undergoing liver resection.

Methods

Perioperative TPO was analyzed prior to liver resection as well as on the first and fifth postoperative day in 46 colorectal cancer patients with liver metastasis (mCRC) as well as 23 hepatocellular carcinoma patients (HCC). Serum markers of liver function within the first postoperative week were used to define liver dysfunction.

Results

While circulating TPO levels significantly increased one day after liver resection in patients without liver cirrhosis (mCRC) (P < 0.001), patients with underlying liver disease (HCC) failed to significantly induce TPO postoperatively. Accordingly, HCC patients had significantly lower TPO levels on POD1 and 5. Similarly, patients with major resections failed to increase circulating TPO levels. Perioperative dynamics of TPO were found to specifically predict liver dysfunction (AUC: 0.893, P < 0.001) after hepatectomy and remained an independent predictor upon multivariate analysis.

Conclusions

We here demonstrate that perioperative TPO dynamics are associated with postoperative LD. Postoperative TPO levels were found to be lowest in high-risk patients (HCC patients undergoing major resection) but showed an independent predictive value. Thus, a dampened TPO increase after liver resection reflects a poor capacity for hepatic recovery and may help to identify patients who require close monitoring or intervention for potential complications.     

Metabolic trajectories based on <Superscript>1</Superscript>H NMR spectra of urines from sheep exposed to nutritional challenges during prenatal and early postnatal life

¹H NMR metabolic profiles of urine from sheep exposed to prenatal nutritional restriction (n = 19) and a control group with normal prenatal nutritional requirements (n = 19), followed by either conventional (n = 10 + 10) or high carbohydrate high fat postnatal diet (n = 9 + 9), were studied. Urine was sampled from 2, 6, 19 and 24-month-old animals receiving differential dietary treatments during the first 6 months and the same normal diet later. Principal component analysis of ¹H NMR spectra (n = 164) showed a V-shaped metabolic trajectory as a function of age and diet, starting with urines with a high amount of glucose, indicative of monogastric-like metabolism, and exhibiting concomitant increase of metabolites related to rumen microflora (mainly glycine conjugates of benzoic and phenylacetic acid) as the ruminal metabolism developed. Urines from young (2-month-old) animals exposed to prenatal undernutrition followed by normal postnatal diet showed metabolic patters that are ahead in time on the metabolic trajectory relative to the prenatal control group. No long-term effects of fetal undernutrition, alone or in combination with postnatal hypernutrition were observed.     

Plasma amino acid imbalance in alcoholic liver cirrhosis

Plasma amino acid concentrations and plasma glucagon and serum insulin levels were studied in male patients with compensated alcoholic and nonalcoholic liver cirrhosis. Age, nutritional status, and liver function tests were similar in both groups; none of the patients presented hepatic encephalopathy. Plasma valine and leucine concentrations were lower, and tyrosine, higher in alcoholic than nonalcoholic liver cirrhosis. As a result, the molar ratios of branched-chain amino acids (BCAA) to aromatic amino acids (AAA) were reduced markedly in this group. Although correlation coefficients comparing BCAA/AAA ratios and KICG in alcoholic and nonalcoholic liver cirrhosis were similar, a steeper regression line was observed in alcoholics. Plasma glucagon and proline levels were significantly higher in alcoholic than nonalcoholic liver cirrhosis, the former correlated with AAA concentrations only in alcoholic liver cirrhosis, but not with BCAA levels. These results indicated that alcoholic liver cirrhosis presented a more deranged plasma amino acid pattern than nonalcoholic, and the amino acid imbalances, except for depressed BCAA and elevated proline, were derived, in part, from the hyperglucagonemia.     

Immunocytochemical study of the hepatic innervation in the rat after partial hepatectomy

Summary The autonomic nervous system in rats has been assessed by means of indirect immunofluorescence using monospecific antibodies to neuron-specific enolase, neurofilaments, glial fibrillary acidic protein and S-100 protein (10 days after partial (70%) hepatectomy). Different groups of rats were studied:group A: 70% resection and normal dual blood supply (n=5);group B: 70% resection with only portal blood to the liver remnant (n=5);group C: 70% resection with only arterial blood to the liver remnant (n=5);group D: sham operated controls (n=5).All rats of groups A and D showed normal liver/body weight ratios after 10 days in contrast to groups B and C where liver weights were 50–60% of the preresection weight. In group A the regeneration process was histologically normal and associated with a remarkable increase of autonomic innervation patterns in the portal triad. In contrast, livers of animals in groups B and C showed under the light microscope features of hepatocyte degeneration associated with a decreased autonomic innervation compared to the controls. The changes are identical in groups B and C, and are therefore irrespective of the type of blood deprivation (arterial or portal).These results support the importance of dual blood supply for an optimal regenerative response in liver remnants after liver resection. We suggest that the autonomic nerve supply of the portal triad plays at least an important permissive role in liver regeneration.     

Effect of transverse thoracic muscle plane block on postoperative cognitive dysfunction after open cardiac surgery: A randomized clinical trial

The transversus thoracis muscle plane (TTMP) block provides effective analgesia in cardiac surgery patients. The aim of this study was to assess whether bilateral TTMP blocks can reduce the incidence of postoperative cognitive dysfunction (POCD) in patients undergoing cardiac valve replacement. A group of 103 patients were randomly divided into the TTM group (n = 52) and the PLA (placebo) group (n = 51). The primary endpoint was the incidence of POCD at 1 week after surgery. Secondary outcome measures included a reduction of intraoperative mean arterial pressure (MAP) >20% from baseline, intraoperative and postoperative sufentanil consumption, length of stay in the ICU, incidence of postoperative nausea and vomiting (PONV), time to first faeces, postoperative pain at 24 h after surgery, time to extubation and the length of hospital stay. Interleukin (IL)-6, TNF-α, S-100β, insulin, glucose and insulin resistance were measured at before induction of anaesthesia, 1, 3and 7 days after surgery. The MoCA scores were significantly lower and the incidence of POCD decreased significantly in TTM group compared with PLA group at 7 days after surgery. Perioperative sufentanil consumption, the incidence of PONV and intraoperative MAP reduction >20% from baseline, length of stay in the ICU, postoperative pain at 24 h after surgery, time to extubation and the length of hospital stay were significantly decreased in the TTM group. Postoperatively, IL-6, TNF-α, S-100β, HOMA-IR, insulin, glucose levels increased and the TTM group had a lower degree than the PLA group at 1, 3 and 7 days after surgery. In summary, bilateral TTMP blocks could improve postoperative cognitive function in patients undergoing cardiac valve replacement.     

Klatskin tumor--results of surgical therapy

Between January 1st 1990 and December 31st 1999, 24 patients affected by Klatskin tumor underwent operation in our department of surgery. According to Bismuth's classification, there were 0 (0%) type I, 5 (21%) type II, 6 (25%) type IIIa, 4 (17%) type IIIb and 9 (37%) type IV tumors. Five patients (21%) were treated by curative resection (group I) while in 14 patients (58%) palliative surgical procedure was performed (group II). In 5 cases (21%) the extension of malignancy did not allowed any procedure (group III). Curative resection for malignant tumors of the hepatic duct bifurcation included wide tumor excision and bile duct resection at the liver hilum (with wedge hepatic resection in one patient) and creation of biliary-enteric anastomosis. Palliative surgical procedure included stent insertion. Jaundice was completely relieved in all patients undergoing resection, since 3 patients (21%) after stenting hadn't satisfactory biliary drainage. There was 1 (20%) perioperative death in the group 1, while in group 2, 5 patients (36%) died postoperatively. In this series, the mean postoperative survival of all patients was 16 months. The mean postoperative survival of patients undergoing localized tumor resection with curative intent was 38 months, in contrast to 10 months for those undergoing operative stent insertion. in addition, only 1 patient from group III, in whom only exploratory surgery were performed survived 7 months, while other 4 patients died in the hospital. This retrospective review suggests that aggressive surgical treatment could improve survival and quality of life in patients suffering from Klatskin tumor.     

Efficiency of adjuvant active specific immunization with Newcastle disease virus modified tumor cells in colorectal cancer patients following resection of liver metastases: results of a prospective randomized trial

Purpose  Metastatic disease is a major cause of mortality in colorectal cancer patients. Even after complete resection of isolated liver metastases, recurrence develops in the majority of patients. Therefore, development of strategies to prevent recurrent liver metastases is of major clinical importance. The present prospectively randomised phase III trial investigates the efficiency of active specific immunotherapy (ASI) after liver resection for hepatic metastases of colorectal cancer. Methods  Patients with histologically confirmed liver metastases from colorectal cancer were randomised to the vaccination or control group. After complete resection of liver metastases, patients randomised to the vaccination group received six doses of Newcastle disease virus (NDV) infected autologous tumour cell vaccine (ATV-NDV). The primary end-point was overall survival, secondary end-points were disease-free survival and metastases-free survival. Results  Fifty-one patients were enrolled in the study with 50 patients available for analysis. The follow-up period was 116.1 ± 23.8 month in the vaccination arm and 112.4 ± 18.5 month in the control group. In the total patient group, no differences in the primary and secondary end-points were detected. Most interestingly, subgroup analysis revealed a significant advantage for vaccinated colon cancer patients with respect to overall survival [hazard ratio: 3.3; 95%, confidence interval (CI): 1.0–10.4; P = 0.042] and metastases-free survival (hazard ratio: 2.7; 95%, CI: 1.0–7.4; P = 0.047) in the intention-to-treat analysis. Conclusion  Active specific immunotherapy in unselected colorectal cancer patients was not effective for prevention of recurrent metastatic disease. However, in colon cancer patients, ASI with ATV-NDV appears to be beneficial prolonging overall and metastases-free survival.     

Classifying the Stage IV Colorectal Cancer: Prognostic Impact of Radical Resection for Colorectal liver Metastases and Proposal for a New Staging System

Currently, there is no universally accepted system to classify the stage IV colorectal cancer. Here, we analyze the prognostic impact of radical resection for colorectal liver metastases and propose a new staging system for stage IV colorectal cancer. A retrospective review was undertaken of 126 consecutive patients who underwent surgical treatment for colorectal liver metastases from January 1997 to January 2004. Based on the overall survival rates (Kaplan–Meier method) and surgical outcomes, we propose a new staging system for stage IV colorectal cancer. Patients were divided into two groups: patients who underwent initial hepatic resections (R0 resection) for liver metastases (group 1, n = 22), and patients who underwent palliative resection for unresectable liver metastases (group 2, n = 104). The overall survival rates in group 1 at 1, 3, and 5 years were 68.2 % (15/22), 40.9 % (9/22), and 18.2 % (4/22), respectively. The overall survival rates in group 2 at 1, 3, and 5 years were 54.8 % (57/104), 16.3 % (17/104), and 0 % (0/104), respectively. There was a significant difference in overall survival rates between both groups (p < 0.05). Based on the study results, we propose a new staging system where all distant metastases are grouped within stage IV and subclassified into resectable (R0 resection) and unresectable stages. Curative surgical treatment is a critical prognostic factor in colorectal liver metastases. The proposed new staging system for stage IV colorectal cancer is simple and is clinically useful to estimate the prognosis.