Prehabilitation in hepato-pancreato-biliary surgery: A systematic review and meta-analysis. A necessary step forward evidence-based sample size calculation for future trials.

INTRODUCTION: Prehabilitation is defined as preoperative conditioning of patients in order to improve post-operative outcomes. Some studies showed an increase in functional recovery following colorectal surgery, but its effect in hepato-pancreato-biliary (HPB) surgery is unclear. The aim of this study was to realize a systematic literature review and meta-analysis on the current available evidence on prehabilitation in HPB surgery. MATERIALS AND METHODS: A systematic review and a metanalysis were carried out on prehabilitation (physical, nutritional and psychological interventions) in HPB surgery (2009-2019). Assessed outcomes were postoperative complications, length of stay (LOS), 30-day readmission, and mortality. MAIN RESULTS: Four studies among the 191 screened were included in this systematic review (3 randomized controlled trials, 1 case-control propensity score study), involving 419 patients (prehabilitation group, n=139; control group, n=280). After pooling, no difference was observed on LOS ((-4.37 days [95% CI: -8.86; 0.13]) or postoperative complications (RR 0.83 [95%CI: 0.62; 1.10]), reported by all the included studies. Two trials reported on readmission rate, but given the high heterogeneity, a meta-analysis was not realized. No deaths were reported among the included studies. CONCLUSION: No effect of prehabilitation programs in HPB surgery was observed on LOS or postoperative complications rate. Future trials with standardized outcomes of measure, and adequately powered samples calculations are thus required. PROSPERO REGISTRATION: CRD42020165218.

Influence of 4 preservation solutions on ICU stay, graft and patient survival following liver transplantation.

OBJECTIVE: The goal of this study was to evaluate the prognostic role of four preservation solutions in liver transplantation (LT). PATIENTS AND METHODS: This is a retrospective study originating from 22 French centers performing LT, registered in the prospective databank of the Cristal Biomedicine Agency between 2008 and 2013. The preservation solutions used were Celsior (CS), Institut Georges Lopez (IGL)-1, Solution de Conservation des Organes et des Tissus (SCOT) 15 and University of Wisconsin (UW) solutions. Exclusion criteria were preservation with unknown or inhomogeneous solutions, or Histidine-tryptophan-ketoglutarate (HTK) solution (representing only 3% of LT). Patient survival was the main endpoint. Secondary endpoints were graft survival and duration of stay in intensive care. RESULTS: Of 6347 LT performed, 4928 were included in this study, for which the distribution of preservation solution was CS (30%), IGL-1 (44%), SCOT 15 (10%) and UW (16%). Patient survival was 86%, 80% and 74% at 1, 3 and 5 years after LT, respectively, without any statistically significant difference between the four solutions (P=0.78). Graft survival was 82%, 75% and 69% at 1, 3 and 5 years after LT, respectively, without any statistically significant difference between the four solutions (P=0.80). Duration of intensive care was different according to the solution used in univariate analysis (P<0.001), but this effect disappeared in multivariate analysis when the center performing the transplantation was accounted for. CONCLUSION: The type of preservation solution used (CS, IGL-1, SCOT 15 or UW) did not have any influence on patient or graft survival after LT.

Postoperative collections after liver surgery: Risk factors and impact on long-term outcomes.

INTRODUCTION: Postoperative collection (PC) can occur after liver surgery, but little is known on their impact on short and long-term outcomes. The aim of this study was to analyse factors predicting the occurrence of PC, the need of drainage and their impact on oncologic outcomes. METHODS: This single-center, cohort-study included adult patients undergoing liver surgery between 2008 and 2017. The primary objective was to determine variables associated with PC occurrence defined by fluid collection on postoperative day-7 CT scan. Secondary objectives were factors predicting drainage requirement, and predictors of overall survival. RESULTS: During the study period 395 patients were included: 53.6% of them (n=210) developed a PC with 12% (n=49) requiring drainage. Variables associated to the occurrence of PC were body mass index>35kg/m2 (OR 8.09, 95%CI (1.50,43.60) P=0.015) and extension of liver surgery (major vs. minor, OR 1.96, 95% CI (1.05,3.64) P<0.034) while laparoscopic approach was associated to a protective role (OR 0.35, 95%CI (0.18,0.67) P=0.001) in the multivariate analysis. The presence of a PC requiring treatment was associated to long-term mortality (OR:1.85, 95% CI (1.15, 2.97) P<0.01) in patients with malignant disease. CONCLUSIONS: Patients undergoing to major open liver surgery with BMI>35kg/m2 have an increased risk to develop a PC: this target population need a systematic imaging in the postoperative period, even if the indication for drainage should be guided by clinical symptoms. Last, the presence of PC requiring treatment has a negative impact on overall survival among patients treated for malignant disease.

Enhanced recovery after liver surgery.

INTRODUCTION: In a majority of cases, enhanced recovery after surgery program (ERP) leads to a reduced rate of postoperative complications and shortened hospital stays following digestive surgery. The program's preoperative, perioperative and postoperative measures are implemented by the members of a motivated multidisciplinary team. Having shown its merits in digestive surgery, ERP would be particularly useful in liver surgery due to the elevated rates of morbidity and mortality this type of operation continues to entail. The objective of this review was to evaluate the efficacy of ERP in liver surgery. METHOD: This is a systematic narrative review of the literature on the efficacy of ERP in liver surgery by laparotomy or laparoscopy. RESULTS: Notwithstanding a number of studies (n=30: 5 randomized trials, 14 cohort studies and 11 meta-analyses) less sizable than with regard to digestive surgery in general and colorectal surgery in particular, analysis of the literature confirms that in liver surgery, ERP is associated with an overall decrease in complications by 30 to 60%, but without improvement in the rates of hospital readmission and postoperative mortality. All of the studies report a reduction in average length of stay (ALOS) by 2.3 days and in functional recovery, a more objective indicator than ALOS, by 2.5 days. As of now, the economic impact of the ERP programs in liver surgery is neither positive nor negative, the above-mentioned savings being counterbalanced by heightened costs for material and equipment. Laparoscopic surgery is independently associated with better outcomes in terms of complications, functional recovery and ALOS; that is why it is important to incorporate this surgical approach in ERP as often as possible. Given a lack of robust evidence, Prehabilitation, which is a preoperative optimization process leading to improved functional reserve, has yet to be assigned a place in ERP programs pertaining to liver surgery. Possible roadblocks to application of an ERP program can be overcome through coordination by a team leader, a motivated multidisciplinary team, training courses and dedicated teaching sessions. CONCLUSION: ERP is a care improvement process that has a major play to play in organization of liver surgery, and its large-scale application is to be recommended.

Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS): impact of the inter-stages course on morbi-mortality and implications for management.

BACKGROUND: Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) was recently developed to induce rapid hypertrophy and reduce post-hepatectomy liver failure in patients with insufficient remnant liver volume (RLV). However, mortality rates >12% have been reported. This study aimed to analyze the perioperative course of ALPPS and to identify factors associated with morbi-mortality. METHODS: Between April 2011 and September 2013, 62 patients operated in 9 Franco-Belgian hepatobiliary centres underwent ALPPS for colorectal metastases (N = 50) or primary tumors, following chemotherapy (N = 50) and/or portal vein embolization (PVE; N = 9). RESULTS: Most patients had right (N = 31) or right extended hepatectomy (N = 25) (median RLV/body weight ratio of 0.54% [0.21-0.77%]). RLV increased by 48.6% [-15.3 to 192%] 7.8 ± 4.5 days after stage1, but the hypertrophy decelerated beyond 7 days. Stage2 was cancelled in 3 patients (4.8%) for insufficient hypertrophy, portal vein thrombosis or death and delayed to ≥9 days in 32 (54.2%). Overall, 25 patients (40.3%) had major complication(s) and 8 (12.9%) died. Fourteen patients (22.6%) had post-stage1 complication of whom 5 (35.7%) died after stage2. Factors associated with major morbi-mortality were obesity, post-stage1 biliary fistula or ascites, and infected and/or bilious peritoneal fluid at stage2. The latter was the only predictor of Clavien ≥3 by multivariate analysis (OR: 4.9; 95% CI: 1.227-19.97; p = 0.025). PVE did not impact the morbi-mortality rates but prevented major cytolysis that was associated with poor outcome. CONCLUSIONS: The inter-stages course was crucial in determining ALPPS outcome. The factors of high morbi-mortality rates associated with ALPPS are linked to the technique complexity.

Increased erythrocyte glutathione peroxidase activity and serum tumor necrosis factor-alpha in HIV-infected patients: relationship to on-going prothrombotic state.

A condition of oxidative stress, due to perturbation of oxidant/antioxidant balance, has been suggested to play a role not only in the pathogenesis of human immunodeficiency virus (HIV) infection, but also in the promotion of a thrombophilic condition. Because various hemostatic dysfunctions usually considered as risk factors for thrombotic events were reported in HIV infection, this study was undertaken to investigate whether the oxidative phenomenon could promote a prothrombotic state in such condition. Erythrocyte glutathione peroxidase (GSH-Px), the major free-radical scavenger enzyme, and serum tumor necrosis factor-alpha (TNF-alpha) were evaluated in 33 consecutive HIV-infected out-patients and 35 matched HIV-negative healthy controls at a distance of any acute episode. Thrombin generation was explored by measuring the plasma levels of prothrombin fragment 1 + 2 (F1 + 2), whereas fibrin degradation products (D-dimer) and plasminogen activator inhibitor (PAI-1) activity were evaluated as indices of plasmin activity and fibrinolytic derangement. The anticoagulant pathway was investigated by measuring the plasma levels of antithrombin and protein C. Erythrocyte GSH-Px activity and serum TNF-alpha were significantly higher in HIV-infected patients when compared to controls. F1 + 2, D-dimer, and PAI-1 activity were increased in HIV-infected patients by comparison with controls. Normal antithrombin, but decreased protein C, was instead detected in HIV-infected patients. In the latter patients, serum TNF-alpha negatively correlated with both erythrocyte GSH-Px activity and plasma D-dimer. On the other hand, a positive correlation was shown between F1 + 2 and D-dimer and between D-dimer and GSH-Px activity. Furthermore, a trend toward increasing levels of GSH-Px with increasing PAI-1 activity was reported. These findings suggest a relationship between erythrocyte oxidative stress and the hypercoagulable condition during HIV infection.

Antigen-specific oligoclonal IgG in AIDS-related cytomegalovirus and toxoplasma encephalitis.

UNLABELLED: We retrospectively studied serum and cerebrospinal fluid (CSF) specimens from AIDS patients with either Cytomegalovirus (2 cases) or Toxoplasma gondii (5 cases) encephalitis. The samples, which had previously proved to be negative for total IgG oligoclonal bands (OCBs), were investigated for antigen-specific OCBs directed to the disease-related opportunistic agent. MATERIAL & METHODS: Paired serum and CSF samples from the given AIDS patients were considered. We undertook affinity immunoblotting of either virus- or protozoan-specific IgG onto antigen-coated nitrocellulose paper after protein separation by agarose isoelectric focusing (IEF). RESULTS: Antigen-specific OCBs to the disease-related opportunistic agent were detected in serum and in CSF samples from all the patients. CONCLUSIONS: During overt AIDS, routine IEF methods may fail to detect OCBs, probably because nonspecific polyclonal hypergammaglobulinemia, which is typical of this disease, reduces their visibility. Our IEF/immunoblotting profiles are characterized by identical serum and CSF bands. The detection of antigen-specific OCBs may support the diagnosis of some opportunistic infections of the central nervous system in AIDS.

Acute Guillain-Barré syndrome associated with asymptomatic HIV infection.

A 25-year-old male drug addict presented with a rapidly progressive ascending tetraplegia, requiring assisted ventilation. One month earlier he had fever (40 degrees C) and asthenia. Cerebrospinal fluid (CSF) examination showed elevated albumin level and albuminocytologic dissociation. HIV testing was positive in both serum and CSF. Plasma exchange therapy only partially improved the symptomatology. After five months the patient remained with a moderate tetraparesis. Differences between this and other cases of Guillain-Barré syndrome in HIV-seropositive patients reported in the literature are discussed.

Tumor necrosis factor alpha levels in serum and cerebrospinal fluid of patients with AIDS.

We used a sensitive enzyme-linked immunosorbent assay technique to measure tumor necrosis factor alpha (TNF alpha) levels in serum and cerebrospinal fluid (CSF) samples from 30 patients infected with human immunodeficiency virus type 1 and from 10 normal controls. We found detectable levels of TNF alpha in 19 of 30 CSF and in 17 of 30 serum samples. The values of TNF alpha ranged between 20-90 pg/ml. All the patients had overt AIDS. More elevated TNF alpha levels in CSF correlate with focal damage within the central nervous system (p less than 0.01). Our results suggest that an intrathecal production of TNF alpha may occur during active inflammation in course of AIDS.

Elevated alpha-tumor necrosis factor levels in spinal fluid from HIV-1-infected patients with central nervous system involvement.

To assess the role of alpha-tumor necrosis factor in the pathogenesis of central nervous system involvement during human immunodeficiency virus type 1 infection, we recorded clinical data and measured alpha-tumor necrosis factor levels in serum and cerebrospinal fluid samples from 45 patients infected with human immunodeficiency virus type 1, classified as group II/III (10), group IV A (5), group IV B (10), and group IV C-1 (20) of the Centers for Disease Control acquired immunodeficiency syndrome classification system and 42 controls. Alpha-tumor necrosis factor was above the limit of detection in only 3 of 15 sera and 3 of 15 cerebrospinal fluid samples from patients in group II/III and group IV A, whereas it was detected in 17 of 30 sera (p less than 0.05) and 22 of 30 cerebrospinal fluid (p less than 0.0002) samples from clinically more advanced patients (group IV B and group IV C-1). Alpha-tumor necrosis factor mean values were 21.5 pg/ml in sera and 50.0 pg/ml in cerebrospinal fluid from group IV B patients and 30.4 pg/ml in sera and 24 pg/ml in cerebrospinal fluid from group IV C-1 patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Phagocytosis of human erythrocytes by Naegleria is not related to species pathogenicity. A phase-contrast cinemicrographic study.

This phase contrast cinemicrographic study evaluated the phagocytic activity of Naegleria spp. (Naegleria fowleri, Naegleria australiensis and Naegleria lovaniensis) towards human red cells. Thus erythrophagocytosis, a marker of pathogeneicity for Entamoeba histolytica, did not correlate with virulence in either the pathogenic or non-pathogenic Naegleria spp. tested. Our study also revealed no quantitative differences in phagocytosis by Naegleria spp. of human erythrocytes.

Isoelectric focusing herpes simplex virus-gB overlay study in brainstem encephalitis.

We report a case of herpetic brainstem encephalitis (HBE) retrospectively diagnosed in adult patient. Conventional immunovirological studies failed to disclose the etiology of this patient's affection. An isoelectric focusing-antigen overlay (IEF-O) technique showed that the target of one of the four cerebrospinal fluid oligoclonal bands was herpes simplex virus (HSV)-1 glycoprotein B, indicating a specific anti-HSV immunoresponse restricted to the CNS. IEF-O may represent a useful support for in vivo diagnosis of HBE.

[Sulprostone in the prevention and therapy of hemorrhage due to postpartal uterine atony]. / Il sulprostone nella prevenzione e terapia della emorragia da atonia uterina post-partum.

Sulprostone (Nalador-Schering) was used on 25 cases of bleeding caused by post-partum atonia that did not respond to conventional uterotonic treatment. The good results obtained led to the use of the drug whenever it was necessary to prevent haemorrhage independent of the risk factors that might cause its onset.

[Visceral and ocular Larva migrans: epidemiologic study, clinical and immunologic findings on 20 cases, adult and child]. / Larva migrans viscérale et oculaire: étude épidémiologique, clinique et immunologique portant sur 20 cas, adultes et enfants.

The authors report a case-study of 20 subjects affected by visceral Larva migrans (VLM) and ocular Larva migrans (OLM). Of the 20 patients, 11 were male, and 9 female (mean age: 45 years); 7 were children, from 1 to 8 years old. Seventeen patients presented clinical and bio-humoral features which could be correlated with VLM syndrome; alongside cases with clearly suggestive symptomatology, in some patients the infection by Toxocara sp. was found to show few or minor symptoms, or even to be asymptomatic and occasionally it was suspected because of a marked peripheral eosinophilia. In 3 cases the infection was exclusively ocular. So far as immunology is concerned, serological tests confirmed in all 20 cases the clinico-epidemiological and/or bio-humoral suspicion; in particular the ELISA IgG test showed high titres in 16 cases, while the RAST showed significant levels of specific IgE in 17 cases. From the therapeutic point of view, the subjects treated were exclusively those presenting a manifest clinical picture: in 5 patients the first choice drug was thiabendazole, with clinical cure in only 2 cases; diethylcarbamazine resolved the clinico-parasitological picture in 1 case; 1 patient is still under treatment with albendazole.

Is tubal rupture a discriminating factor in the surgical conservative treatment of ectopic pregnancy?

217 women have been submitted to a surgical intervention for ectopic pregnancy in the years 83 - 84 - 85 in five hospitals in Piedmont. The rupture has been observed in 147 cases (67%). The percentage of women who presented a rupture was higher among those who underwent annexiectomy (75%), average among those who underwent salpingectomy (69%) and lower in case of conservative intervention (52%). Owing to these rather high percentages, we cannot state that the rupture is a discriminating factor as far as it concerns the choice of intervention, even if a fairly more conservative orientation is evident in case of unruptured tube.

Ectopic pregnancy: which treatment? Analysis of 217 cases.

The Authors describe the various types of treatment performed on 217 cases of ectopic pregnancy examined, which took place in the years 1983 - 84 - 85 in five among the main Hospital in Piedmont. 136 salpingectomies (62%), 41 annexiectomies (18%), 40 conservative interventions (20%) were performed. In most cases the destructive intervention was performed in the presence of a tubal rupture; no meaningful relations between the location and the type of surgical treatment have been found in the ectopic pregnancy. Conservative interventions have been more frequent on young women (under 35: 97%) and desiring children either because nullipara (65%) or because uniparous (27%). The highest number of conservative interventions was performed in the largest of the five Hospitals examined (23 cases: 57%). There is therefore a remarkable relation between diagnostic and therapeutic means and the possibility of performing the surgery most appropriate to the specific requirements of each case.

Comparative evaluation of ectopic pregnancy surgical treatment between a specialized hospital and a general hospital.

The surgical approaches followed in cases of ectopic pregnancy by the operators in two centres in Piedmont, one specialized in ostetrics and gynecology, the other a general county hospital are taken into consideration and compared. 131 cases have been registered in Turin and 30 in Biella. The salpingectomy has been performed on most cases in both centres with 56.5% and 66% respectively in the specialized Hospital and in the General one. The annexiectomy has been chosen for 25%. The intervention aiming at preserving the tube has been chosen for 17.5% in Turin and 34% in Biella. The most discriminating factor in choosing the type of intervention is mainly based on the patient's amnestic history, and therefore on her age, parity, any preceeding tube intervention and also on her desire for children.