Cost-benefit analysis of an enhanced recovery protocol for pancreaticoduodenectomy.

BACKGROUND: Enhanced recovery after surgery (ERAS) programmes have been shown to decrease complications and hospital stay. The cost-effectiveness of such programmes has been demonstrated for colorectal surgery. This study aimed to assess the economic outcomes of a standard ERAS programme for pancreaticoduodenectomy. METHODS: ERAS for pancreaticoduodenectomy was implemented in October 2012. All consecutive patients who underwent pancreaticoduodenectomy until October 2014 were recorded. This group was compared in terms of costs with a cohort of consecutive patients who underwent pancreaticoduodenectomy between January 2010 and October 2012, before ERAS implementation. Preoperative, intraoperative and postoperative real costs were collected for each patient via the hospital administration. A bootstrap independent t test was used for comparison. ERAS-specific costs were integrated into the model. RESULTS: The groups were well matched in terms of demographic and surgical details. The overall complication rate was 68 per cent (50 of 74 patients) and 82 per cent (71 of 87 patients) in the ERAS and pre-ERAS groups respectively (P = 0·046). Median hospital stay was lower in the ERAS group (15 versus 19 days; P = 0·029). ERAS-specific costs were €922 per patient. Mean total costs were €56 083 per patient in the ERAS group and €63 821 per patient in the pre-ERAS group (P = 0·273). The mean intensive care unit (ICU) and intermediate care costs were €9139 and €13 793 per patient for the ERAS and pre-ERAS groups respectively (P = 0·151). CONCLUSION: ERAS implementation for pancreaticoduodenectomy did not increase the costs in this cohort. Savings were noted in anaesthesia/operating room, medication and laboratory costs. Fewer patients in the ERAS group required an ICU stay.

Rheological behaviour of polyoxometalate-doped lyotropic lamellar phases.

We study the influence of nanoparticle doping on the lyotropic liquid crystalline phase of the industrial surfactant Brij®30 (C12E4) and water, doped with spherical polyoxometalate nanoparticles smaller than the characteristic dimensions of the host lamellar phase. We present viscometry and in situ rheology coupled with small-angle X-ray scattering data that show that, with increasing doping concentration, the nanoparticles act to decrease the shear viscosity of the lamellar phase, and that a shear-induced transition to a multilamellar vesicle "onion" phase is pushed to higher shear rates, and in some cases completely suppressed. X-ray data reveal that the nanoparticles remain encapsulated within the membranes of the vesicles, thus indicating a viable method for the fabrication of nanoparticle incorporating organic vesicles.

[Pancreaticoduodenectomy: indications, results and management of complications]. / Duodénopancréatectomie céphalique: indications, résultats et prise en charge des complications.

Pancreaticoduodenectomy is a major procedure in visceral surgery. Post-operative mortality is around 5% in high-volume hospitals, thanks to improvement in global patients care. Morbidity remains high though. The treatment of complications most often require a multidisciplinary approach. Delayed gastric emptying, intraabdominal abscesses and pancreatic fistulas are the most frequent complications. Post-pancreatectomy hemorrhage, although more rare, is a severe and dreadful event. Despite its morbidity, duodenopancreatectomy significantly improves survival of patients with biliopancreatic cancer. Early recognition of these complications and a prompt treatment increase the safety of this procedure.

[New treatments in vascular diseases]. / Nouveautés en chirurgie vasculaire.

In superficial venous insufficiency, surgery remains the treatment of choice. Endovenous therapies are a minimal invasive alternative, whose long-term results are not demonstrated yet. In the treatment of abdominal aortic aneurysm, endovascular repair (EVAR) and laparoscopic approach are comparatively studied with open repair, to define their precise indications. In occlusive arterial disease, endovascular treatment offers inferior results in term of durability and patency, however with a decrease in morbidity and mortality.

Physical properties of aqueous suspensions of goethite (alpha-FeOOH) nanorods. Part I: In the isotropic phase.

Depending on volume fraction, aqueous suspensions of goethite (alpha-FeOOH) nanorods form a liquid-crystalline nematic phase (above 8.5%) or an isotropic liquid phase (below 5.5%). In this article, we investigate by small-angle X-ray scattering, magneto-optics, and magnetometry the influence of a magnetic field on the isotropic phase. After a brief description of the synthesis and characterisation of the goethite nanorod suspensions, we show that the disordered phase becomes very anisotropic under a magnetic field that aligns the particles. Moreover, we observe that the nanorods align parallel to a small field (< 350 mT), but realign perpendicular to a large enough field (> 350 mT). This phenomenon is interpreted as due to the competition between the influence of the nanorod permanent magnetic moment and a negative anisotropy of magnetic susceptibility. Our interpretation is supported by the behaviour of the suspensions in an alternating magnetic field. Finally, we propose a model that explains all experimental observations in a consistent way.

Physical properties of aqueous suspensions of goethite (alpha-FeOOH) nanorods. Part II: In the nematic phase.

At volume fractions larger than 8.5%, aqueous suspensions of lath-like goethite (alpha-FeOOH) nanorods form a lyotropic nematic phase. In this article, we first discuss the nematic ordering within statistical-physics models of the isotropic/nematic phase transition. We then describe the influence of a magnetic field on the nematic phase. Because the nanorods bear permanent magnetic moments, the nematic suspensions have dipolar order and very low Frederiks thresholds. Moreover, the nematic phase aligns parallel to a small magnetic field but realigns perpendicular to a high field because of a competition between the permanent moments of the nanorods and their negative anisotropy of magnetic susceptibility. This magneto-optical study of the nematic phase is completely consistent with that of the isotropic phase of the same suspensions published in Part I (this issue, p. 291). Besides, we demonstrate the field-induced biaxiality of a nematic single domain aligned perpendicular to the field. We also describe here preliminary experiments where an a.c. electric field is applied to the nematic phase. Both field amplitude and frequency were found to control the alignment direction and homeotropic-to-planar alignment transitions were observed. From this data, simple models were used to estimate some physical constants of the nematic phase.

Hepatitis B virus DNA in sera and liver tissue of HBsAg negative patients with chronic hepatitis C.

BACKGROUND/AIMS: Hepatitis B virus (HBV) DNA has been detected in HBsAg-negative patients with hepatitis C. We determined the rate and explored the clinical significance of HBsAg negative HBV coinfections in Austrian patients with chronic hepatitis C. METHODS: Sera (n=82, group I) or liver tissue (n=16, group II) from 98 HBsAg negative Austrian patients with chronic hepatitis C were examined for HBV DNA by nested polymerase chain reaction (PCR). For control purposes, sera from 15 patients with chronic HBV infection (8 HBsAg positive, 7 HBsAg negative, all HBV PCR positive) were examined. RESULTS: HBV DNA was detected in 22% of sera and 19% of liver tissue specimens of patients with chronic hepatitis C. No significant difference in mean aminotransferase values, markers of HBV infection, inflammatory disease activity, or degree of hepatic fibrosis was observed in patients with or without HBV DNA. Anti-HBc alone as a marker of past HBV infection was more frequent in chronic hepatitis C patients compared to control individuals. Negative HCV PCR was more common (p=0.009) among patients with positive HBV PCR in serum. When examining repeat sera for HBV DNA, positive results were obtained in previously negative, but also negative results in previously positive patients. CONCLUSIONS: Coinfection with HBV can be demonstrated by PCR in a considerable number of HBsAg negative Austrian patients with chronic hepatitis C. HBV infection seems to suppress HCV replication even in HBsAg negative patients with dual infection. HBV coinfection in HCV infected patients cannot be excluded by negative HBsAg status alone. Repeat PCR examinations are needed to exclude dual infections.

Prevalence of GBV-C/HGV-RNA, virus genotypes, and anti-E2 antibodies in autoimmune hepatitis.

OBJECTIVE: We investigated the prevalence of hepatitis G-RNA (GBV-C/HGV-RNA), a recently cloned new flavivirus, and of antibodies to the envelope 2 antigen (anti-E2), a marker of past infection, in patients with autoimmune hepatitis, and compared it with the prevalence in patients with chronic viral hepatitis and healthy control individuals. METHODS: Sera of 63 patients with autoimmune hepatitis were studied for the presence of GBV-C/HGV-RNA by reverse-transcription polymerase chain reaction and for anti-E2 by enzyme-linked immunosorbent assay. GBV-C/HGV genotypes were determined by genome sequencing. RESULTS: Patients with autoimmune hepatitis had a similar high prevalence of GBV-C/HGV-RNA and anti-E2 antibodies as patients with chronic viral hepatitis B or C. GBV-C/HGV-RNA was found significantly more often in patients with autoimmune hepatitis (11%, p = 0.045), hepatitis B (16%, p = 0.004), or hepatitis C (21%, p = 0.001) than in healthy controls (2%). The prevalence of anti-E2 antibodies in patients with autoimmune hepatitis was not different from healthy controls (17% vs 13%, NS). The various subtypes of autoimmune hepatitis had similar prevalence rates of GBV-C/HGV-RNA as patients with liver-kidney microsomal antibody-positive hepatitis C. All of our anti-E2+ (GBV-C/HGV-RNA-) patients were positive for anti-smooth-muscle antibody, whereas only 29% of GBV-C/HGV-RNA+ (anti-E2-) patients were positive (p = 0.025). All seven of the GBV-C/HGV-RNA+ patients with autoimmune hepatitis had genotype 2a, which is also the most prevalent genotype in our region. CONCLUSION: The prevalence of GBV-C/HGV-RNA is significantly increased in patients with autoimmune hepatitis, compared with healthy controls, and is similar to the increased prevalence seen in chronic hepatitis B or C patients. Anti-E2 positivity was associated with antibodies against smooth-muscle antigen in all cases. All GBV-C/HGV+ autoimmune hepatitis patients were infected with genotype 2a.

Prevalence of hepatitis G-virus infection in alcohol abusing patients with and without liver cirrhosis.

BACKGROUND: Hepatitis G (GBV-C/HGV) is an RNA-virus belonging to the flavivirus family and is capable of inducing hepatitis in rare cases. Its importance as a co-factor in the pathogenesis of liver disease needs to be clarified. AIMS: To determine the prevalence of HGV in chronic alcoholics with and without liver cirrhosis. PATIENTS: 86 alcoholics, 44 with liver cirrhosis and 42 without liver cirrhosis, were investigated; 93 healthy individuals served as controls. METHODS: Serum was tested for GBV-C/HGV-RNA by reverse-transcription polymerase chain reaction (RT-PCR) and for anti-E2, a marker of resolved GBV-C/HGV infection, by ELISA. GBV-C/HGV-RNA positive samples were sequenced and the GBV-C/HGV subtype determined. RESULTS: Eight out of 86 (9.3%) alcoholics were GBV-C/HGV-RNA positive, as compared to 2 out of 93 (2.2%) healthy controls (n. s.). Twenty-one (24.4%) alcoholics had anti-E2 in serum, whereas this antibody was found in 12 (12.9%) healthy persons only (n. s.). However, significantly more alcoholic patients (33.7%) than healthy controls (15.1%) had past or present contact with GBV-C/HGV (p = 0.006). 11.4% of alcoholic patients with liver cirrhosis and 7.1% of alcoholic patients without liver cirrhosis showed GBV-C/HGV-RNA. 34.1% of alcoholic patients with liver cirrhosis and 16.6% of alcoholic patients without liver cirrhosis had anti-E2. Among the 44 patients with liver cirrhosis, 8 out of 11 (72.7%) patients with variceal bleeding, but only 11 of 33 patients without bleeding had contact with GBV-C/HGV (p = 0.05). Seven out of 8 GBV-C/HGV-RNA positive alcoholics had genotype 2a, 1 had type 1a of GBV-C/HGV. CONCLUSION: Alcoholic patients have a significantly higher contact rate with GBV-C/HGV as compared to healthy controls. Alcoholics with liver cirrhosis tend to be more frequently infected than alcoholic patients without liver cirrhosis. A previous variceal bleeding episode is significantly associated with GBV-C/HGV infection.

GBV-C/HGV in hemodialysis patients: anti-E2 antibodies and GBV-C/HGV-RNA in serum and peripheral blood mononuclear cells.

Hepatitis G virus (GBV-C/HGV), a recently identified RNA virus adds to the risk of parenteral transmitted viral infections in hemodialysis patients. We studied the prevalence of GBV-C/HGV-RNA in serum and peripheral blood mononuclear cells (PMNC) by reverse transcription-polymerase chain reaction (RT-PCR) and determined antibodies against the envelope protein E2 of GBV-C/HGV by ELISA. A total of 119 dialysis patients were studied. GBV-C/HGV-RNA was found in 16 of 119 patients (13%) as compared with 2% of healthy controls (P = 0.014). Two of the 16 GBV-C/HGV-RNA+ patients were co-infected with HCV, and none was positive for HBV-DNA. In 38% of serum GBV-C/HGV-RNA+ patients GBV-C/HGV-RNA was also detected in PMNC. In addition, GBV-C/ HGV-RNA was identified in PMNC of 2 patients negative for GBV-C/ HGV-RNA in serum. Twenty-four patients had anti-E2 antibodies in serum (20%), but were GBV-C/HGV-RNA-. In addition, two of the 16 GBV-C/HGV-RNA+ patients were concomitantly positive for anti-E2 antibodies. Only one of the 16 GBV-C/HGV infected patients had elevated aminotransferases; this patient was co-infected with hepatitis C virus. GBV-C/HGV-RNA positivity was independent on duration of hemodialysis, but GBV-C/HGV-RNA+ patients had received more units of blood in the past. Combined data of past contact, as assessed by anti-E2 antibodies, and present infection, documented by GBV-C/HGV-RNA, indicate a high overall exposure to GBV-C/HGV in dialysis patients.

Lack of specificity of albumin-mRNA-positive cells as a marker of circulating hepatoma cells.

The aim of the study was to assess the specificity of albumin-messenger RNA (mRNA)-positive cells in peripheral blood as an indicator for circulating malignant hepatocytes. Albumin-mRNA-positive cells in the peripheral blood mononuclear cell (PMNC) fraction were detected by reverse-transcription polymerase chain reaction (RT-PCR). Albumin-mRNA-positive cells in PMNC were found in 12 of 19 (63%) patients with hepatocellular carcinoma, but also in 22 of 25 (88%) patients with chronic hepatitis without evidence for hepatoma, and in 18 of 19 (94%) of patients with acute viral hepatitis. In addition, 8 of 28 (28%) of healthy control individuals had also albumin-mRNA-positive cells in peripheral blood. PMNC known to be spontaneously negative for albumin-mRNA could be induced in vitro to transcribe albumin-mRNA after activation with a variety of substances such as interleukin-1 (IL-1) plus concanavalin A (Con A), IL-2, bacterial lipopolysaccharide, platelet derived growth factor, alpha-fibroblast growth factor, or hepatocyte growth factor. These results show that the majority of patients with acute and chronic liver disease without evidence for hepatocellular carcinoma has albumin-mRNA-positive cells in their PMNC fraction indicating the nonspecificity of that parameter for the presence of circulating malignant hepatocytes. In addition, in vitro experiments suggest that PMNC are capable of transcribing mRNA for albumin at a low level after activation. In vivo-activated PMNC are likely to be the source of positivity in healthy controls, patients with nonmalignant acute and chronic liver disease, and patients with hepatocellular carcinoma.

Whipple's disease: comparison of histology with diagnosis based on polymerase chain reaction in four consecutive cases.

BACKGROUND: Polymerase chain reaction (PCR) based detection of species specific sequences of the 16S rRNA gene of Tropheryma whippelii is a recently described method for diagnosis of Whipple's disease. AIMS: Comparison of histology with PCR in mucosal samples of patients with Whipple's disease before, during, and after treatment. Detection of T whippelii in peripheral blood mononuclear cells as a non-invasive test for infection. METHODS: Four consecutive patients with histologically proven Whipple's disease were studied prospectively. RESULTS: In untreated patients biopsy specimens taken from regions with PAS positive macrophages gave a positive result with PCR for T whippelii; however, a PCR signal was also found in tissue biopsy specimens from mucosal regions with negative histology. In two of the patients the PCR performed with nucleic acids extracted from peripheral blood mononuclear cells was positive. After treatment with sulfamethoxazole/trimethoprim the PCR became negative after one month in two patients and after two months in the third patient treated, whereas PAS positive macrophages were found throughout the treatment period in two patients and disappeared in only one of them thereafter. CONCLUSIONS: Detection of T whippelii specific sequences based on the PCR is useful to confirm the diagnosis, is able to detect a positive signal in samples taken from histologically negative mucosal areas, and can be used to monitor treatment. The PCR can sometimes be positive in peripheral blood mononuclear cells, but this cellular compartment cannot be taken as a substitute for duodenal biopsy specimens in the diagnosis of Whipple's disease.

Prevalence of hepatitis G virus in patients with hepatocellular carcinoma.

Hepatitis B virus (HBV) and hepatitis C virus (HCV) are known to be associated with hepatocellular carcinoma (HCC). In this study, we investigated the prevalence of the newly described hepatitis G virus (HGV) in patients with HCC. The sera of 85 patients (66 male, 19 female, 61 +/- 11 years) with HCC were studied for the presence of HGV RNA by reverse transcriptase-polymerase chain reaction. Seventeen (20%) of 85 patients with HCC, 10 (16%) of 61 patients with chronic hepatitis B without HCC and 14 (20%) of 68 patients with chronic hepatitis C without HCC were infected with HGV, a significantly higher proportion when compared with two (2%) of 85 healthy controls (P < 0.01). When grouped according to the underlying cause of liver disease, HCC patients with HBV infection (33%), HCV infection (21%), alcoholic liver disease (17%), or cryptogenic cirrhosis (15%) had similar serum levels of HGV RNA. Four of the 17 (24%) HGV-positive patients with HCC were coinfected with HBV and six (35%) with HCV; thus, 59% of HGV-positive patients with HCC were coinfected with other hepatotropic viruses. Seven (41%) HGV-positive patients were infected with HGV only. Patients with HGV infection were more likely to have a history of blood transfusion than patients without HGV infection (P = 0.024). Hence, the prevalence of HGV is significantly higher in patients with HCC in comparison with the healthy population.

HBV and HCV genome in peripheral blood mononuclear cells in patients undergoing chronic hemodialysis.

Patients undergoing chronic hemodialysis are at risk for infection with hepatitis B virus (HBV) and hepatitis C virus (HCV). As peripheral blood mononuclear cells (PMNC) are known to be susceptible to infection of both HBV and HCV, assessment of viral genomes in those cells could uncover occult infections not detected by serologic methods or virus determination in serum. We investigated all 67 patients undergoing chronic hemodialysis at a single dialysis unit by PCR for the presence of HBV or HCV genomes in serum as well as in PMNC. None of the 67 patients was HBsAg positive or showed HBV-DNA in serum, but in 5 patients HBV-DNA in PMNC was detected as the only marker of HBV-infection; those patients were also anti-HBc negative. In 9 patients HCV-RNA was positive in serum; in 5 of those patients it was also found in PMNC. Three of these infected patients were negative for anti-HCV. One other patient had no anti-HCV or HCV-RNA in serum, but was positive for HCV-RNA in PMNC. Thus, in 6 patients (8.9%) undergoing chronic hemodialysis we found evidence of infection with HBV or HCV by detecting viral genomes in PMNC without the presence of viremia, antigenemia or specific viral antibodies in serum. The detection of viral genomes in PMNC could be useful in the positive identification of additional potentially infectious patients.

Increased in vitro production and serum levels of the soluble lipopolysaccharide receptor sCD14 in liver disease.

Elevated concentrations of lipopolysaccharide have been found in serum of patients with severe parenchymal liver disease and its toxic effect is thought to involved in hemodynamic disturbances seen in cirrhosis. A soluble form of the receptor (sCD14) for lipopolysaccharide is present in serum and is released by stimulated macrophages, indicating macrophage activation. We investigated sCD14 serum levels and in vitro production by lipopolysaccharide stimulated peripheral blood monocytes in patients with various liver diseases. In acute viral hepatitis serum sCD14 levels were significantly higher during the first 2 weeks after onset of jaundice (n=11; 3.6 +/- 0.9 microg /ml (mean +/- SD)) than in healthy control individuals (n=52; 2.5 +/- 0.7 microg/ml; p<0.001). These elevated serum levels corresponded to enhanced in vitro production of sCD14 by lipopolysaccharide-stimulated peripheral blood monocytes (n=11; 365 +/- 262 ng/ml) as compared to control monocytes (n=52; 228 +/- 74 ng/ml; p=0.02). Similarly, patients with alcoholic cirrhosis had significantly increased sCD14 serum levels (n=31; 4.5 +/- 3.2 microg/ml; p<0.001) and in vitro sCD14 production by lipopolysaccharide-stimulated monocytes (291 +/- 153 ng/ml; p=0.014). Serum sCD14 levles correlated with the severity of disease (Child A: 2.6 +/- 1.0 microg/ml; Child B: 4.4 +/- 2.1 microg/ml; Child C: 7.8 +/- 5.1 micro/ml; Anova: p=0.001). Patients with chronic viral hepatitis had only slightly elevated serum sCD14 levels (n=17; 2.9 +/- 0.7 microg/ml; p=0.01) and increased in vitro production of sCD14 by peripheral blood monocytes (320 +/- 128 ng/ml; p<0.001). The elevated serum concentration of sCD14 in alcoholic cirrhosis and acute and chronic viral hepatitis points to an incrased macrophage activation in these diseases. sCD14 from serum is able to associate with cells not expressing membrane CD14, such as endothelial cells, allowing those cells to bind and respond to lipopolysaccharide. Elevated levels of sCD14 could in this way contribute to the toxic effects of lipopolysaccharide in severe liver disease.

Soluble CD8 and soluble CD4 antigens in viral hepatitis and alcoholic cirrhosis.

Serum levels and production of soluble CD8 and soluble CD4 antigens by peripheral blood mononuclear cells were determined in patients with alcoholic cirrhosis and acute or chronic viral hepatitis. Patients with chronic viral hepatitis had significantly increased soluble CD8 serum levels (n = 18; 734 +/- 143 U/ml) (mean +/- SD) compared to healthy controls (n = 80; 312 +/- 141 U/ml; p < 0.001) and patients with alcoholic cirrhosis (n = 12; 505 +/- 256 U/ml; p = 0.006), whose soluble CD8 concentrations were also higher than controls (p < 0.001). In contrast, soluble CD4 antigen serum levels were similar in all groups. In addition, patients with chronic hepatitis showed an increased production of soluble CD8, but not soluble CD4, after mitogenic stimulation of their peripheral blood mononuclear cells compared to controls or patients with alcoholic cirrhosis. Patients with acute viral hepatitis, studied within the first 2 weeks after onset of jaundice, showed markedly elevated serum concentrations of soluble CD8 (n = 4; 807 +/- 379 U/ml; p < 0.001 vs. controls), but not soluble CD4. In addition, nine patients with chronic hepatitis C were studied during and after treatment with alpha interferon. Soluble CD8 serum concentrations of six treatment responders were not found to be different from the low levels seen in controls, whereas three non-responders had increased soluble CD8 levels which were similar to levels in untreated patients with chronic hepatitis C. After interferon-alpha therapy ended, a significant elevation of soluble CD8 serum concentrations was observed in four relapsing patients, which paralleled the serum ALT increase.(ABSTRACT TRUNCATED AT 250 WORDS)

[The effectiveness of standardized follow-up studies after resection of non-small cell bronchial carcinoma]. / Die Effektivität schematisierter Nachsorgeuntersuchungen nach Resektion eines nichtkleinzelligen Bronchialkarzinoms.

The outcomes of 190 patients in whom a non-small-cell bronchogenic carcinoma had been resected with curative intent in the Department of Surgery, University of Cologne, between 1. 1. 1977 and 31. 12. 1987 were analysed retrospectively. Sixty-seven (35%) of these patients underwent regular, 64 (34%) irregular, and 59 (31%) no standardized follow-up programmes. During follow-up procedures tumour recurrences were detected in 33 patients (25%). Thirteen (39%) of these recurrences were completely asymptomatic at the time of diagnosis. Three recurrences (9%) were resected with curative intent, but the patients died between 14 and 17 months later due to recurrent disease. Seven recurrences (21%) were treated by radiotherapy, three (9%) by chemotherapy, and 20 patients (61%) received no oncologic therapy. The survival rates after diagnosis of recurrence were not affected by the type of treatment or by the presence of clinical symptoms. There is no evidence that long-term results following resection of non-small-cell bronchogenic carcinoma can be improved by regular and standardized follow-up programmes. The observed incidence of postoperative pulmonary disorders and the patients' self-assessment underline the necessity for postoperative care after resection of bronchogenic carcinoma. Apart from clinical studies, follow-up should primarily focus on individual symptoms and should no longer include standardized investigations in asymptomatic patients except occasional X-ray checks of the thorax.