Major liver resections,perioperative issues and posthepatectomy liver failure:A comprehensive update for the anesthesiologist

Significant advances in surgical techniques and relevant medium-and long-term outcomes over the past two decades have led to a substantial expansion in the indications for major liver resections.To support these outstanding results and to reduce perioperative complications,anesthesiologists must address and master key perioperative issues(preoperative assessment,proactive intraoperative anesthesia strategies,and implementation of the Enhanced Recovery After Surgery approach).Intensive care unit monitoring immediately following liver surgery remains a subject of active and often unresolved debate.Among postoperative complications,posthepatectomy liver failure(PHLF)occurs in different grades of severity(A-C)and frequency(9%-30%),and it is the main cause of 90-d postoperative mortality.PHLF,recently redefined with pragmatic clinical criteria and perioperative scores,can be predicted,prevented,or anticipated.This review highlights:(1)The systemic consequences of surgical manipulations anesthesiologistsmust respond to or prevent,to positively impact PHLF(a proactive approach);and(2)the maximal intensivetreatment of PHLF,including artificial options,mainly based,so far,on Acute Liver Failure treatment(s),to buytime waiting for the recovery of the native liver or,when appropriate and in very selected cases,toward livertransplant.Such a clinical context requires a strong commitment to surgeons,anesthesiologists,and intensivists towork together,for a fruitful collaboration in a mandatory clinical continuum.

肩关节镜辅助下小切口肩峰成形及肩袖修补

目的 探讨肩关节镜辅助下小切口肩袖修补手术的临床应用价值。方法 本组 2 6例患者 ,在关节镜下完成肩峰成形 ,然后在小切口内对肩袖完全破裂的 18例患者行肌腱 骨隧道缝合 ,对部分破裂的 8例患者行肌腱 肌腱缝合。结果 术后随访 2 1～ 4 8个月 (平均 37.5个月 ) ,所有患者均无术后感染及肩关节粘连发生 ,肩关节疼痛 ,特别是夜间痛明显改善 ,手术疗效满意。UCLA评分由术前平均 2 0 .1分改善至术后 31.6分。结论 本术式可确定肩关节面一侧肩袖破裂的部位及深度 ,且不破坏三角肌的连续性。手术效果好 ,患者可较早进行功能煅练 ,功能恢复快。

Intestinal microbiota in inflammatory bowel disease:Friend of foe?

Inflammatory bowel disease （IBD） arises from disruption of immune tolerance to the gut commensal microbiota, leading to chronic intestinal inflammation and mucosal damage in genetically predisposed hosts. In healthy individuals the intestinal microbiota have a symbiotic relationship with the host organism and possess important and unique functions, including a metabolic function （i.e. digestion of dietary compounds and xenobiotics, fermentation of undigestible carbohydrates with production of short chain fatty acids）, a mucosal barrier function （i.e. by inhibiting pathogen invasion and strengthening epithelial barrier integrity）, and an immune modula- tory function （i.e. mucosal immune system priming and maintenance of intestinal epithelium homeostasis）. A fine balance regulates the mechanism that allows co- existence of mammals with their commensal bacteria. In IBD this mechanism of immune tolerance is impaired because of several potential causative factors. The gut microbiota composition and activity of IBD patients are abnormal, with a decreased prevalence of dominant members of the human commensal microbiota （i.e. Clostridium IXa and IV groups, Bacteroides, bifldobacteria） and a concomitant increase in detrimental bacteria （i.e. sulphate-reducing bacteria, Escherichia coll. The observed dysbiosis is concomitant with defectiveinnate immunity and bacterial killing （i.e. reduced mucosal defensins and IgA, malfunctioning phagocytosis） and overaggressive adaptive immune response （due to ineffective regulatory T cells and antigen presenting cells）, which are considered the basis of IBD pathogen- esis. However, we still do not know how the interplay between these parameters causes the disease. Studies looking at gut microbial composition, epithelial integrity and mucosal immune markers in genotyped IBD populations are therefore warranted to shed light on this obscure pathogenesis.

Familial aggregation in inflammatory bowel disease:Is it genes or environment?

Inflammatory bowel disease (IBD) develops in genetically susceptible individuals due to the influence of environmental factors, leading to an abnormal recognition of microbiota antigens by the innate immune system which triggers an exaggerated immune response and subsequent bowel tissue damage. IBD has been more frequently found in families, an observation that could be due to either genetic, environmental or both types of factors present in these families. In addition to expanding our knowledge on IBD pathogenesis, defining the specific contribution to familial IBD of each one of these factors might have also clinical usefulness. We review the available evidence on familial IBD pathogenesis.

Narrow-band imaging endoscopy to assess mucosal angiogenesis in inflammatory bowel disease: A pilot study

AIM: To investigate whether narrow band imaging (NBI) is a useful tool for the in vivo detection of angiogenesis in inflammatory bowel disease (IBD) patients. METHODS: Conventional and NBI colonoscopy was performed in 14 patients with colonic inflammation (8 ulcerative colitis and 6 Crohn’s disease). Biopsy samples were taken and CD31 expression was assayed immuno- histochemically; microvascular density was assessed by vessel count. RESULTS: In areas that were endoscopically normal but positive on NBI, there was a significant (P < 0.05) increase in angiogenesis (12 ± 1 vessels/field vs 18 ± 2 vessels/field) compared with areas negative on NBI. In addition, in areas that were inflamed on white light endoscopy and positive on NBI, there was a significant (P < 0.01) increase in vessel density (24 ± 7 vessels/f ield) compared with NBI-negative areas.CONCLUSION: NBI may allow in vivo imaging of intestinal angiogenesis in IBD patients.

Helicobacter pylori eradication and reflux disease onset:Did gastric acid get "crazy"?

Gastroesophageal reflux disease (GORD) is highly prevalent in the general population.In the last decade,a potential relationship between Helicobacter pylori (H.pylori) eradication and GORD onset has been claimed.The main putative mechanism is the gastric acid hypersecretion that develops after bacterial cure in those patients with corpus-predominant gastritis.We performed a critical reappraisal of the intricate pathogenesis and clinical data available in this field.Oesophagitis onset after H.pylori eradication in duodenal ulcer patients has been ascribed to a gastric acid hypersecretion,which could develop following body gastritis healing.However,the absence of an acid hypersecretive status in these patients is documented by both pathophysiology and clinical studies.Indeed,duodenal ulcer recurrence is virtually abolished followingH.pylori eradication.In addition,intra-oesophageal pH recording studies failed to demonstrated increased acid reflux following bacterial eradication.Moreover,oesophageal manometric studies suggest that H.pylori eradication would reduce-rather than favor-acid reflux into the oesophagus.Finally,data of clinical studies would suggest that H.pylori eradication is not significantly associated with eitherreflux symptoms or erosive oesophagitis onset,some data suggesting also an advantage in curing the infection when oesophagitis is already present.Therefore,the legend of "crazy acid" remains-as all the others a fascinating,but imaginary tale.

Metrically measuring liver biopsy:A chronic hepatitis B and C computer-aided morphologic description

AIM： To describe a quantitative analysis method for liver biopsy sections with a machine that we have named ＂Dioguardi Histological Metriser＂ which automatically measures the residual hepatocyte mass （including hepatocytes vacuolization）, inflammation, fibrosis and the loss of liver tissue tectonics.METHODS： We analysed digitised images of liver biopsy sections taken from 398 patients, The analysis with Dioguardi Histological Metriser was validated by comparison with semi-quantitative scoring system.RESULTS： The method provides： （1） the metrical extension in two-dimensions （the plane） of the residual hepatocellular set, including the area of vacuoles pertinent to abnormal lipid accumulation; （2） the geo- metric measure of the inflammation basin, which distinguishes intra-basin space and extra-basin dispersed parenchymal leukoo/tes; （3） the magnitude of collagen islets, （which were considered truncated fractals and classified into three degrees of magnitude）; and （4） the tectonic index that quantifies alterations （disorders） in the organization of liver tissue. Dioguardi Histological Metriser machine allows to work at a speed of 0.1 mm^2/s, scanning a whole section in 6-8 min.CONCLUSION： The results are the first standardized metrical evaluation of the geometric properties of the parenchyma, inflammation, fibrosis, and alterations in liver tissue tectonics of the biopsy sections. The present study confirms that biopsies are still valuable, not only for diagnosing chronic hepatitis, but also for quantifying changes in the organization and order of liver tissue structure.

Mucosal biomarkers in inflammatory bowel disease:Key pathogenic players or disease predictors?

Inflammatory bowel diseases(IBDs) are chronic inflammatory disorders of the bowel,including ulcerative colitis and Crohn's disease.A single etiology has not been identified,but rather the pathogenesis of IBD is very complex and involves several major and minor contributors,employing different inflammatory pathways which have different roles in different patients.Although new and powerful medical treatments are available,many are biological drugs or immunosuppressants,which are associated with significant side effects and elevated costs.As a result,the need for predicting disease course and response to therapy is essential.Major attempts have been made at identifying clinical characteristics,concurrent medical therapy,and serological and genetic markers as predictors of response to biological agents.Only few reports exist on how mucosal/tissue markers are able to predict clinical behavior of the disease or its response to therapy.The aim of this paper therefore is to review the little information available regarding tissue markers as predictors of response to therapy,and reevaluate the role of tissue factors associated with disease severity,which can eventually be ranked as "tissue factor predictors".Five main categories are assessed,including mucosal cytokines and chemokines,adhesion molecules and markers of activation,immune and non-immune cells,and other mucosal components.Improvement in the design and specificity of clinical studies are mandatory to be able to classify tissue markers as predictors of disease course and response to specific therapy,obtain the goal of achieving "personalized pathogenesisoriented therapy" in IBD.

Risk of postoperative recurrence and postoperative management of Crohn's disease

Crohn's disease (CD) is a chronic inflammatory disease of the digestive tract with systemic manifestations. Etiology is unknown, even if immunological, genetic and environmental factors are involved. The majority of CD patients require surgery during their lifetime due to progressive bowel damage, but, even when all macroscopic lesions have been removed by surgery, the disease recurs in most cases. Postoperative management represents therefore a crucial mean for preventing recurrence. Several drugs and approaches have been proposed to achieve this aim. Endoscopic inspection of the ileocolic anastomosis within 1 year from surgery is widely encouraged, given that endoscopic recurrence is one of the greatest predictors for clinical recurrence. A strategy should be planned only after stratifying patients according to their individual risk of recurrence, avoiding unnecessary therapies when possible benefits are reduced, and selecting high-risk patients for more aggressive intervention.

Helicobacter pylori and functional dyspepsia: An unsolved issue?

Patients with Helicobacter pylori (H. pylori) infection may complain of dyspeptic symptoms without presence of macroscopic lesions on gastroduodenal mucosa. Such a condition is usually recognized as functional dyspepsia, and different pathogenetic mechanisms are involved. The role of H. pylori in these patients is controversial. Several trials assessed the potential role of H. pylori eradication in improving dyspeptic symptoms, and data of some meta-analyses demonstrated that cure of infection is associated with a small (10%), but significant therapeutic gain as compared to placebo. The reason for which dyspeptic symptoms regress in some patients following bacterial eradication, but persist in others remains unclear. Regrettably, trials included in the meta-analyses are somewhat different for study design, definition of symptoms, assessment of symptoms changes, and some may be flawed by potential pitfalls. Consequently, the information could be not consistent. We critically reviewed the main available trials, attempting to address future research in this field

History and evolution of the use of oral mucosa for urethral reconstruction

We report here the history and evolution of the use of oral mucosa in reconstructive urethral surgery since it was first used for urethroplasty in 1894.Since that time,many authors have contributed to develop,improve and popularize the use of oral mucosa as a substitute material.Paediatric urologists should be considered pioneers on the use of oral mucosa as they used it to repair primary and failed hypospadias.The use of oral mucosa to repair penile and bulbar urethral strictures was described,for the first time,in 1993.Important evolutions in the technique for harvesting oral mucosa from the cheek were reported in 1996.Today,oral mucosa is considered the gold standard material for any type of anterior urethroplasty in a one-or two-stage repair due to its biological and structural characteristics that make it a highly versatile that is adaptable to any environment required by the reconstructive urethral surgery.As the future approaches,tissue engineering techniques will provide patients with new materials originating from the oral epithelial mucosal cells,which are cultured and expanded into a scaffold.However,the path to reach this ambitious objective is still long and many difficulties must be overcome along the way.

Pancreatic metastases:An increasing clinical entity

Pancreatic metastases,although uncommon,have been observed with increasing frequency recently,especially by high-volume pancreatic surgery centers.They are often asymptomatic and detected incidentally or during follow-up investigations even several years after the re-moval of the primary tumor.Renal cell cancer represents the most common primary tumor by far,followed by colorectal cancer,melanoma,sarcoma and lung cancer.Pancreatic metastasectomy is indicated for an isolated and resectable metastasis in a patient fit to tolerate pancreatectomy.Both standard and atypical pancreatic resection can be performed:a resection strategy providing adequate resection margins and maximal tissue preservation of the pancreas should be pursued.The effectiveness of resection for pancreatic metastases is mainly dependent on the tumor biology of the primary cancer;renal cell cancer is associated with the best outcome with a 5-year survival rate greater than 70%.

Immune-mediated bile duct injury:The case of primary biliary cirrhosis

Autoimmune cholangitis would be the appropriate name to define the immune-mediated bile duct injury following the breakdown of tolerance to mitochondrial proteins and the appearance of serum autoantibodies and autoreactive T cells.Nevertheless,the conditionis universally named primary biliary cirrhosis(PBC).The disease etiology and pathogenesis remain largely unknown despite the proposed lines of evidence.One twin study and numerous epidemiology reportssuggest that both a susceptible genetic background and environmental factors determine disease onsetwhile a recent genome-wide association study proposed highly significant associations with several commongenetic polymorphisms in subgroups of patients.Specific infectious agents and chemicals may contribute to the disease onset and perpetuation in a geneticallysusceptible host,possibly through molecular mimicry.Importantly,several murine models have been proposed and include strains in which PBC is genetically determined or induced by immunization with chemicals and bacteria.From a pathogenetic standpoint,new exciting data have demonstrated the unique apoptotic features of bile duct cells that allow the mitochondrial autoantigens to be taken up in their intact form within apoptotic blebs.We are convinced that the application of the most recent molecular techniques will soon pro-vide developments in PBC etiology and pathogenesis with likely implications in diagnostics and therapeutics.

Open label trial of granulocyte apheresis suggests therapeutic efficacy in chronically active steroid refractory ulcerative colitis

AIM： To study the efficacy, safety, and feasibility of a granulocyte adsorptive type apheresis system for the treatment of patients with chronically active ulcerative colitis despite standard therapy. METHODS： An open label multicenter study was carried out in 39 patients with active ulcerative colitis （CAI 6-8） despite continuous use of steroids （a minimum total dose of 400 mg prednisone within the last 4 wk）. Patients received a total of five aphereses using a granulocyte adsorptive technique （Adacolumn, Otsuka Pharmaceutical Europe, UK）. Assessments at wk 6 and during follow-up until 4 mo comprised clinical （CAI） and endoscopic （EI） activity index, histology, quality of life （IBDQ）, and laboratory tests. RESULTS： Thirty-five out of thirty-nine patients were qualified for intent-to-treat analysis. After the apheresis treatment at wk 6, 13/35 （37.1%） patients achieved clinical remission and 10/35 （28.6%） patients had endoscopic remission （CAI〈4, EI〈4）. Quality of life （IBDQ） increased significantly （24 points, P〈0.01） at wk 6. Apheresis could be performed in all but one patient. Aphereses were well tolerated, only one patient experienced anemia. CONCLUSION： In patients with steroid refractory ulcerative colitis, five aphereses with a granulocyte/ monocyte depleting filter show potential short-term efficacy. Tolerability and technical feasibility of the procedure are excellent.

Liver fibrosis and tissue architectural change measurement using fractal-rectified metrics and Hurst's exponent

AIM： To provide the accurate alternative metrical means of monitoring the effects of new antiviral drugs on the reversal of newly formed collagen. METHODS： Digitized histological biopsy sections taken from 209 patients with chronic C virus hepatitis with different grade of fibrosis or cirrhosis, were measured by means of a new, rapid, user-friendly, fully computeraided method based on the international system meter rectified using fractal principles. RESULTS： The following were described： geometric perimeter, area and wrinkledness of fibrosis; the collation of the Knodell, Sheuer, Ishak and METAVIR scores with fractal-rectified metric measurements; the meaning of the physical composition of fibrosis in relation to the magnitude of collagen islets; the intra- and inter-biopsy sample variability of these parameters; the ＂staging＂ of biopsy sections indicating the pathway covered by fibrosis formation towards its maximum known value; the quantitative liver tissue architectural changes with the Hurst exponent. CONCLUSION： Our model provides the first metrical evaluations of the geometric properties of fibrosis and the quantitative architectural changes of the liver tissue. The representativeness of histological sections of the whole liver is also discussed in the light of the results obtained with the Hurst coefficient.

Intestinal metaplasia surveillance:Searching for the roadmap

Atrophic gastritis and intestinal metaplasia(IM) of the stomach are common and are associated with an increased risk for gastric cancer.In the absence of guidelines,a pragmatic management has been performed in Western countries in patients with these premalignant conditions.Recently,formal European guidelines have been delivered on this topic.Basically,it has been recommended that patients with extensive atrophic gastritis(AG) and/or extensive IM should be offered endoscopic surveillance every 3 years.On the contrary,no scheduled endoscopic/histological control has been advised for those patients with precancerous conditions confined to the antrum.In this commentary,we highlighted some potential weaknesses in the management formally recommended by the new guidelines.In detail,we discussed that AG and IM patients do not share the same gastric cancer risk,at least in Western countries,deserving a different approach.Some factors significantly associated with gastric cancer risk,such as IM type,first-degree family history of gastric cancer,and smoking habit have not been considered in tailoring the endoscopic follow-up.Finally,some data would suggest that a 3-year follow-up in patients with extensive gastric precancerous conditions could result in an inadequate secondary prevention.

Localized intra-abdominal fibromatosis of the small bowel mimicking a gastrointestinal stromal tumor: A case report

Intra-abdominal fibromatosis （IAF） is a benign mesenchymal lesion that can occur throughout the gastrointestinal tract. Although rare, it is the most common primary tumor of the mesentery and can develop at any age. We describe a rare case of primary IAF involving the mesentery and small bowel which clinically, macroscopically and histologically mimicked malignant gastrointestinal stromal tumor （GIST）. This report highlights the fact that benign IAF can be misdiagnosed as a malignant GIST localized in the mesentery or arising from the intestinal wall. Their diagnostic discrimination is essential because of their very different biological behaviors and the fact that the introduction of effective therapies involving tyrosine kinase inhibitor ST1571 （imatinib mesylate） has greatly changed the clinical approach to intra-abdominal stromal spindle cell tumors.

Balanced propofol sedation administered by nonanesthesiologists:The first Italian experience

AIM:To assess the efficacy and safety of a balanced approach using midazolam in combination with propofol,administered by nonanesthesiologists,in a large series of diagnostic colonoscopies.METHODS:Consecutive patients undergoing diagnostic colonoscopy were sedated with a single dose of midazolam(0.05 mg/kg)and lowdose propofol(starter bolus of 0.5 mg/kg and repeated boluses of 10 to 20 mg).Induction time and deepest level of sedation,adverse and serious adverse events,as well as recovery times,were prospectively assessed.Cecal intubation and adenoma detection rates were also collected.RESULTS:Overall,1593 eligible patients were included.The median dose of propofol administered was 70 mg(range:40120 mg),and the median dose of midazolam was 2.3 mg(range:24 mg).Median induction time of sedation was 3 min(range:14 min),and median recovery time was 23 min(range:1040 min).A moderate level of sedation was achieved in 1561(98%) patients,whilst a deep sedation occurred in 32(2%) cases.Transient oxygen desaturation requiring further oxygen supplementation occurred in 8(0.46%;95% CI:0.2%0.8%)patients.No serious adverse event was observed.Cecal intubation and adenoma detection rates were 93.5%and 23.4%(27.8%for male and 18.5%for female,subjects),respectively.CONCLUSION:A balanced sedation protocol provided a minimalization of the dose of propofol needed to target a moderate sedation for colonoscopy,resulting in a high safety profile for nonanesthesiologist propofol sedation.

Optimized management of advanced hepatocellular carcinoma:Four long-lasting responses to sorafenib

The therapeutic options for hepatocellular carcinoma (HCC) have been so far rather inadequate.Sorafenib has shown an overall survival benefit and has become the new standard of care for advanced HCC.Nevertheless,in clinical practice,some patients are discontinuing this drug because of side effects,and misinterpretation of radiographic response may contribute to this.We highlight the importance of prolonged sorafenib ad-ministration,even at reduced dose,and of qualitative and careful radiographic evaluation.We observed two partial and two complete responses,one histologically confirmed,with progression-free survival ranging from 12 to 62 mo.Three of the responses were achieved following substantial dose reductions,and a gradual change in lesion density preceded or paralleled tumor shrinkage,as seen by computed tomography.This report supports the feasibility of dose adjustments to allow prolonged administration of sorafenib,and highlights the need for new imaging criteria for a more appropriate characterization of response in HCC.

Retrograde-viewing device improves adenoma detection rate in colonoscopies for surveillance and diagnostic workup

AIM:To determine which patients might benefit most from retrograde viewing during colonoscopy through subset analysis of randomized,controlled trial data.METHODS:The Third Eye Retroscope Randomized Clinical Evaluation(TERRACE) was a randomized,controlled,multicenter trial designed to evaluate the efficacy of a retrograde-viewing auxiliary imaging device that is used during colonoscopy to provide a second video image which allows viewing of areas on the proximal aspect of haustral folds and flexures that are difficult to see with the colonoscope's forward view.We performed a post-hoc analysis of the TERRACE data to determine whether certain subsets of the patient population would gain more benefit than others from use of the device.Subjects were patients scheduled for colonoscopy for screening,surveillance or diagnostic workup,and each underwent same-day tandem examinations with standard colonoscopy(SC) and Third Eye colonoscopy(TEC),randomized to SC followed by TEC or vice versa.RESULTS:Indication for colonoscopy was screening in 176/345 subjects(51.0%),surveillance after previous polypectomy in 87(25.2%) and diagnostic workup in 82(23.8%).In 4 subjects no indication was specified.Previously reported overall results had shown a net additional adenoma detection rate(ADR) with TEC of 23.2% compared to SC.Relative risk(RR) of missing adenomas with SC vs TEC as the initial procedure was 1.92(P = 0.029).Post-hoc subset analysis shows additional ADRs for TEC compared to SC were 4.4% for screening,35.7% for surveillance,55.4% for diagnostic and 40.7% for surveillance and diagnostic combined.The RR of missing adenomas with SC vs TEC was 1.11(P = 0.815) for screening,3.15(P = 0.014) for surveillance,8.64(P = 0.039) for diagnostic and 3.34(P = 0.003) for surveillance and diagnostic combined.Although a multivariate Poisson regression suggested gender as a possibly significant factor,subset analysis showed that the difference between genders was not statistically significant.Age,bowel prep quality and withdrawal time did not significantly affect the RR of missing adenomas with SC vs TEC.Mean sizes of adenomas detected with TEC and SC were similar at 0.59 cm and 0.56 cm,respectively(P = NS).CONCLUSION:TEC allows detection of significantly more adenomas compared to SC in patients undergoing surveillance or diagnostic workup,but not in screening patients(ClinicalTrials.gov Identifier:NCT01044732).