Propofol sedation in routine endoscopy:A case series comparing target controlled infusion vs manually controlled bolus concept

BACKGROUND Many studies have addressed safety and effectiveness of non-anaesthesiologist propofol sedation(NAPS)for gastrointestinal(GI)endoscopy Target controlled infusion(TCI)is claimed to provide an optimal sedation regimen by avoiding under-or oversedation.AIM To assess safety and performance of propofol TCI sedation in comparison with nurse-administered bolus-sedation.METHODS Fouty-five patients undergoing endoscopy under TCI propofol sedation were prospectively included from November 2016 to May 2017 and compared to 87 patients retrospectively included that underwent endoscopy with NAPS.Patients were matched for age and endoscopic procedure.We recorded time of sedation and endoscopy,dosage of medication and adverse events.RESULTS There was a significant reduction in dose per time of propofol administered in the TCI group,compared to the NAPS group(8.2±2.7 mg/min vs 9.3±3.4 mg/min;P=0.046).The time needed to provide adequate sedation levels was slightly but significantly lower in the control group(5.3±2.7 min vs 7.7±3.3 min;P<0.001),nonetheless the total endoscopy time was similar in both groups.No differences between TCI and bolus-sedation was observed for mean total-dosage of propofol rate as well as adverse events.CONCLUSION This study indicates that sedation using TCI for GI endoscopy reduces the dose of propofol necessary per minute of endoscopy.This may translate into less adverse events.However,further and randomized trials need to confirm this trend.

Medical management of metabolic and cardiovascular complications after liver transplantation

Liver transplantation represents the only curative option for patients with endstage liver disease,fulminant hepatitis and advanced hepatocellular carcinoma.Even though major advances in transplantation in the last decades have achieved excellent survival rates in the early post-transplantation period,long-term survival is hampered by the lack of improvement in survival in the late post transplantation period(over 5 years after transplantation).The main etiologies for late mortality are malignancies and cardiovascular complications.The latter are increasingly prevalent in liver transplant recipients due to the development or worsening of metabolic syndrome and all its components(arterial hypertension,dyslipidemia,obesity,renal injury,etc.).These comorbidities result from a combination of pre-liver transplant features,immunosuppressive agent side-effects,changes in metabolism and hemodynamics after liver transplantation and the adoption of a sedentary lifestyle.In this review we describe the most prevalent metabolic and cardiovascular complications present after liver transplantation,as well as proposing management strategies.

Inflammatory myofibroblastic tumor of the liver:A case report and review of literature

BACKGROUND Inflammatory myofibroblastic tumors of the liver(IMTL)are extremely rare neoplasms and very little is known about their clinical presentation,pathogenesis,and biological behavior.Due to their absolute rarity,it is almost impossible to obtain a definite diagnosis without histological examination.Because of their intermediate biological behavior with the risk for local recurrence and metastases,surgical resection is recommend whenever IMTL is suspect.CASE SUMMARY We herein present a case of an otherwise healthy 32-year-old woman who presented with intermittent fever,unclear anemia,malaise and right flank pain 4 mo postpartum.The liver mass in segment IVa/b was highly FDG avid in the positron emission tomography-computed tomography.Hepatic resection was performed achieving a negative resection margin and an immediate resolution of all clinical symptoms.Histological analysis diagnosed the rare finding of an inflammatory myofibroblastic tumor of the liver and revealed cytoplasmic anaplastic lymphoma kinase expression by immunohistochemistry.Twelve months follow-up magnetic resonance imaging showed no recurrence and no metastases in the fully recovered patient.CONCLUSION IMTLs are extremely rare and difficult to diagnose.Due to their intermediate biological behavior,surgical resection should be perform whenever feasible and patients should be followed-up in order to detect recurrence and metastasis as early as possible.

Computer planned, image-guided combined resection and ablation for bilobar colorectal liver metastases

For patients with extensive bilobar colorectal liver metastases(CRLM),initial surgery may not be feasible and a multimodal approach including microwave ablation(MWA)provides the only chance for prolonged survival.Intraoperative navigation systems may improve the accuracy of ablation and surgical resection of so-called"vanishing lesions",ultimately improving patient outcome.Clinical application of intraoperative navigated liver surgery is illustrated in a patient undergoing combined resection/MWA for multiple,synchronous,bilobar CRLM.Regular follow-up with computed tomography(CT)allowed for temporal development of the ablation zones.Of the ten lesions detected in a preoperative CT scan,the largest lesion was resected and the others were ablated using an intraoperative navigation system.Twelve months post-surgery a new lesion(SegⅣa)was detected and treated by trans-arterial embo-lization.Nineteen months post-surgery new liver and lung metastases were detected and a palliative chemotherapy started.The patient passed away four years after initial diagnosis.For patients with extensive CRLM not treatable by standard surgery,navigated MWA/resection may provide excellent tumor control,improving longer-term survival.Intraoperative navigation systems provide precise,real-time information to the surgeon,aiding the decision-making process and substantially improving the accuracy of both ablation and resection.Regular follow-ups including 3D modeling allow for early discrimination between ablation zones and recurrent tumor lesions.

Diarrhea after bariatric procedures:Diagnosis and therapy

Diarrhea after bariatric procedures, mainly those with malabsorptive elements including Roux-Y Gastric Bypass and Biliopancreatic Diversion, is common and an essential determinant of quality of life and microand macronutrient deficiencies. Bariatric surgery is the only sustainably successful method to address morbid obesity and its comorbidities, particularly gaining more and more importance in the specific treatment of diabetic patients. Approximately half a million procedures are annually performed around the world, with numbers expected to rise drastically in the near future. A multitude of factors exert their influence on bowel habits; preoperative comorbidities and procedure-related aspects are intertwined with postoperative nutritional habits. Diagnosis may be challenging owing to the characteristics of postbariatric surgery anatomy with hindered accessibility of excluded segments of the small bowel and restriction at the gastric level. Conventional testing measures, if available, generally yield low accuracy and are usually not validated in this specific population. Limited trials of empiric treatment are a practical alternative and oftentimes an indispensable part of the diagnostic process. This review provides an overview of causes for chronic post-bariatric surgery diarrhea and details the particularities of its diagnosis and treatment in this specific patient population. Topics of current interest such as the impact of gut microbiota and the influence of bile acids on morbid obesity and especially their role in diarrhea are highlighted in order to provide a better understanding of the specific problems and chances of future treatment in post-bariatric surgery patients.

Perianal fistulodesis–A pilot study of a novel minimally invasive surgical and medical approach for closure of perianal fistulae

BACKGROUND Perianal fistulae strongly impact on quality of life of affected patients.AIM To challenge and novel minimally invasive treatment options are needed.METHODS Patients with Crohn’s disease(CD)in remission and patients without inflammatory bowel disease(non-IBD patients)were treated with fistulodesis,a method including curettage of fistula tract,flushing with acetylcysteine and doxycycline,Z-suture of the inner fistula opening,fibrin glue instillation,and Zsuture of the outer fistula opening followed by post-operative antibiotic prophylaxis with ciprofloxacin and metronidazole for two weeks.Patients with a maximum of 2 fistula openings and no clinical or endosonographic signs of a complicated fistula were included.The primary end point was fistula healing,defined as macroscopic and clinical fistula closure and lack of patient reported fistula symptoms at 24 wk.RESULTS Fistulodesis was performed in 17 non-IBD and 3 CD patients,with a total of 22 fistulae.After 24 wk,all fistulae were healed in 4 non-IBD and 2 CD patients(overall 30%)and fistula remained closed until the end of follow-up at 10-25 mo.In a secondary per-fistula analysis,7 out of 22 fistulae(32%)were closed.Perianal disease activity index(PDAI)improved in patients with fistula healing.Low PDAI was associated with favorable outcome(P=0.0013).No serious adverse events were observed.CONCLUSION Fistulodesis is feasible and safe for perianal fistula closure.Overall success rates is at 30%comparable to other similar techniques.A trend for better outcomes in patients with low PDAI needs to be confirmed.

Treatment options for spontaneous and postoperative sclerosing mesenteritis

Sclerosing mesenteritis is a rare pathology with only a few described cases in the literature. The etiology is unclear; however, several potential triggers, including abdominal surgery and abdominal trauma, have been discussed. The pathology includes a benign acute or chronic inflammatory process affecting the adipose tissue of the mesenterium. Despite it being a rare disease, sclerosing mesenteritis is an important differential diagnosis in patients after abdominal surgery or patients presenting spontaneously with signs of acute inflammation and abdominal pain. We present here three cases with sclerosing mesenteritis. In two cases, sclerosing mesenteritis occurred postoperatively after abdominal surgery. One patient was treated because of abdominal pain and specific radiological signs revealing spontaneous manifestation of sclerosing mesenteritis. So far there are no distinct treatment algorithms, so the patients were treated differently, including steroids, antibiotics and watchful waiting. In addition, we reviewed the current literature on treatment options for this rare disease.

Malignant solitary fibrous tumor involving the liver

Solitary fibrous tumors are predominantly benign and are most commonly found in the thoracic cavity and pleura; while reports exist in the literature of malignant solitary fibrous tumors and those located in extrathoracic organs, these cases are considered extremely rare. Herein, a case is reported of a malignant solitary fibrous tumor involving the liver that was diagnosed and treated in a 62-year-old woman. The patient presented with complaints of upper abdominal pain and unintentional weight loss. Computed tomography scan of the abdomen revealed a remarkably large mass, measuring 15 cm × 10 cm × 20 cm, which appeared to be unrelated to any particular organ. The intraoperative finding of a wide communication with the left liver suggested hepatic origin, and served as an indicator for tumor resection via left hemihepatectomy. The diagnosis of solitary fibrous tumor and its malignant nature was confirmed by histological and immunohistochemical examination of the resected tissues. Hepatic solitary fibrous tumor is very rare, and surgery remains the mainstay of treatment. Due to limited reports of such tumors in the literature, little can be said about the benefit of adjuvant therapy and prognosis for the rare cases with malignant histological findings.

Hepatocellular carcinoma in a non-cirrhotic patient with Wilson's disease

We report the exceptional case of hepatocellular carcinoma in a non-cirrhotic patient, whose Wilson's disease was diagnosed at the unusual age of 58 years. The liver histology revealed macrovesicular steatosis with fibrosis, but no cirrhosis. The disease was treated with D-penicillamine for 3 years until acute discomfort in the right upper quadrant led to detection of multifocal hepatocellular carcinoma, which was successfully resected. The histological examination confirmed the malignant nature of the 4 lesions, which were classified according to Edmondson and Steiner as poorly differentiated hepatocellular carcinoma grade 3. The non-tumoral parenchyma showed 80% steatosis with ballooned cells, lobular inflammation, septal fibrosis but no cirrhosis. Hepatocellular carcinoma is rare in Wilson's disease, especially in the absence of cirrhosis. The literature's 28 published cases are reviewed and the contributory role of copper in the hepatocarcinogenic process is discussed.

Combined treatments in hepatocellular carcinoma:Time to put them in the guidelines?

The time for battling cancer has never been more suitable than nowadays and fortunately against hepatocellular carcinoma(HCC)we do have a far-reaching arsenal.Moreover,because liver cancer comprises a plethora of stages-from very early to advanced disease and with many treatment options–from surgery to immunotherapy trials–it leaves the clinician a wide range of options.The scope of our review is to throw light on combination treatments that seem to be beyond guidelines and to highlight these using evidence-based analysis of the most frequently used combination therapies,discussing their advantages and flaws in comparison to the current standard of care.One particular combination therapy seems to be in the forefront:Transarterial chemoembolization plus ablation for medium-size non-resectable HCC(3-5 cm),which is currently at the frontier between Barcelona Clinic Liver Cancer classification A and B.Not only does it improve the outcome in contrast to each individual therapy,but it also seems to have similar results to surgery.Also,the abundance of immune checkpoint inhibitors that have appeared lately in clinical trials are bringing promising results against HCC.Although the path of combination therapies in HCC is still filled with uncertainty and caveats,in the following years the hepatology and oncology fields could witness an HCC guideline revolution.

Alfapump®implantable device in management of refractory ascites:An update

Refractory ascites(RA)is a frequent and life-threatening complication of cirrhosis.In selected patients with RA,transjugular intrahepatic portosystemic shunt(TIPS)placement and liver transplantation(LT)are currently considered the best therapeutic alternatives to repeated large volume paracentesis.In patients with a contraindication to TIPS or LT,the alfapump®system(Sequana Medical,Ghent,Belgium)has been developed to reduce the need for iterative paracentesis,and consequently to improve the quality of life and nutritional status.We report here recent data on technical progress made since the first implantation,the efficacy and tolerance of the device,the position of the pump in the therapeutic arsenal for refractory ascites,and the grey areas that remain to be clarified regarding the optimal selection of patients who are potential candidates for this treatment.

Hepatocyte apoptosis fragment product cytokeratin-18 M30 level and non-alcoholic steatohepatitis risk diagnosis:an international registry study

Background:Liver biopsy for the diagnosis of non-alcoholic steatohepatitis(NASH)is limited by its inherent invasiveness and possible sampling errors.Some studies have shown that cytokeratin-18(CK-18)concentrations may be useful in diagnosing NASH,but results across studies have been inconsistent.We aimed to identify the utility of CK-18 M30 concentrations as an alternative to liver biopsy for non-invasive identification of NASH.Methods:Individual data were collected from 14 registry centers on patients with biopsy-proven non-alcoholic fatty liver disease(NAFLD),and in all patients,circulating CK-18 M30 levels were measured.Individuals with a NAFLD activity score(NAS)≥5 with a score of≥1 for each of steatosis,ballooning,and lobular inflammation were diagnosed as having definite NASH;individuals with a NAS≤2 and no fibrosis were diagnosed as having non-alcoholic fatty liver(NAFL).Results:A total of 2571 participants were screened,and 1008(153 with NAFL and 855 with NASH)were finally enrolled.Median CK-18 M30 levels were higher in patients with NASH than in those with NAFL(mean difference 177 U/L;standardized mean difference[SMD]:0.87[0.69–1.04]).There was an interaction between CK-18 M30 levels and serum alanine aminotransferase,body mass index(BMI),and hypertension(P<0.001,P=0.026 and P=0.049,respectively).CK-18 M30 levels were positively associated with histological NAS in most centers.The area under the receiver operating characteristics(AUROC)for NASH was 0.750(95%confidence intervals:0.714–0.787),and CK-18 M30 at Youden’s index maximum was 275.7 U/L.Both sensitivity(55%[52%–59%])and positive predictive value(59%)were not ideal.Conclusion:This large multicenter registry study shows that CK-18 M30 measurement in isolation is of limited value for non-invasively diagnosing NASH.

Accuracy of non-invasive liver stiffness measurement and steatosis quantification in patients with severe and morbid obesity

Background:Vibration controlled transient elastography(VCTE)and controlled attenuation parameter(CAP™)have shown reliable performance predicting fibrosis and steatosis in normal-to overweight patients but have not been validated in severe to morbid obesity.This study aimed at determining the accuracy of VCTE,CAP™and the composite score FibroScan-AST(FAST)in patients with a body mass index(BMI)of≥35 kg/m^(2).Methods:Patients scheduled for bariatric-metabolic surgery underwent preoperative VCTE/CAP™measurement,and intraoperative liver biopsy.The feasibility and accuracy of VCTE,CAP™and the composite score FAST were retrospectively analysed to evaluate fibrosis,steatosis and active fibrotic non-alcoholic steatohepatitis[NASH+non-alcoholic fatty liver disease(NAFLD)activity score≥4+fibrosis grade≥2]using per protocol(PP)and intent to diagnose(ITD)calculation.Results:In total,170 patients(median BMI 44.4 kg/m²)were included in the study.Liver biopsy showed NASH,simple steatosis,and normal livers in 60.6%(n=103),28.8%(n=49),and 10.6%(n=18),respectively.VCTE and CAP™delivered reliable results in 90.6%(n=154/170)and 90.5%(n=134/148).The AUC(PP)of VCTE,CAP™,and FAST were 0.687(≥F2),0.786(≥F3),0.703(≥S2),0.738(S3),and 0.780(active fibrotic NASH).The AUC increased to 0.742(≥F2),0.842(≥F3),0.712(≥S2),0.780(S3),and 0.836(active fibrotic NASH)in patients below the median BMI of 44.4 kg/m².Conclusions:VCTE,CAP™and FAST show acceptable accuracy for the detection of fibrosis,steatosis and NASH in a real-life cohort of patients with obesity.Accuracy improves in patients with a BMI<44.4 kg/m^(2).

肝硬化和门脉高压的诊断:影像学、非侵入性纤维化标志物和肝脏活检

肝硬化的概念一直在不断演进,现在已经明确的是,代偿期与失代偿期肝硬化预后是完全不同的。进展期慢性肝病(ACLD)这一称谓能更好地反应肝脏组织学变化的进程,比如,即使肝硬化形成了,肝脏组织学仍会继续进展;而在去除病因后,肝脏也可能会在组织学上逆向转好。对于代偿期ACLD,门脉高压标志着疾病进展到了一个并发症高危期,需要准确评估和治疗。在一些复杂的临床情况下,用以诊断肝硬化(肝脏活检)和门脉高压(肝静脉压力梯度检测)等侵入性检查仍然是至关重要的,但由于各种非侵入性检查方法在常规病例中的广泛应用,侵入性检查的临床需求已大大降低。本文对纤维化标志物、弹性成像和影像学等非侵入性检查方法的应用情况、主要优缺点进行了综述。

Fasciola hepatica in a country of low incidence: a tricky diagnosis

Background:Fasciola hepatica is a foodborne trematode present worldwide.Definitive hosts are mostly ruminants such as cattle and sheep,as well as humans.In Switzerland,Fasciola infection in humans is rare.Unfortunately,many patients are likely to undergo multiple unnecessary investigations before the parasite is suspected and fascioliasis diagnosed,especially if symptoms are unspecific.Methods:Retrospective analysis of all patients diagnosed with Fasciola hepatica at the University Hospital of Bern between 2005 and 2018.Diagnosis was positive if a positive serology and/or eggs in stool samples correlated with clinical presentation(symptoms and/or imaging).Patients were excluded if serology was weakly positive and another diagnosis more likely.Personal data,laboratory results,imaging,proposed treatment and outcome were collected from patient files.Results:Sixty patients had a positive serology during this time period.Forty-seven of them had a more plausible alternative diagnosis and were not included in the study,leaving 13 patients for analyses;46.2%(6/13)were male,mean age was 45.8 years old(range,17-80 years old).Four patients(4/13,30.8%)were asymptomatic,nine(9/13,69.2%)presented with symptoms ranging from right upper quadrant abdominal pain(44.4%)and generalized pruritus(33.3%)to weight loss and night sweats(33.3%).The mean duration of symptoms until correct diagnosis was 8.9 months(range,1-48 months).Five patients(5/13,38.5%)had documented eosinophilia,four(4/13,30.8%)elevated liver enzymes and seven(7/13,53.8%)elevated cholestasis parameters.Mean antibody level on serology was 88 AU/mL(range,3-134 AU/mL).Ultrasound was used most frequently(7/13,53.8%),followed by magnetic resonance imaging(4/13,30.8%),computed tomography and endoscopic retrograde cholangiopancreatography(3/13,23.1%).The most common findings were bile duct dilatation,followed by hepatic lesions.Treatment consisted of Triclabendazole 10 mg/Kg.One patient needed a second treatment course for persistent disease.There were no recurrences.Conclusions:With a low incidence of Fasciola hepatica in Switzerland,correct diagnosis is often substantially delayed.Raising awareness among Swiss physicians is paramount,and a higher level of suspicion necessary when confronted with unspecific symptoms or liver imaging,thus avoiding a long delay in diagnosis,as well as unnecessary tests.

肝硬化患者门静脉血栓形成

门静脉血栓形成(PVT)在肝硬化患者中较为常见,尽管PVT相关的严重并发症(如肠系膜缺血)很罕见,但一旦出现足以危胁生命。目前PVT的临床意义、诊断和治疗仍未明确,尚处于探讨中。本文对PVT的分级、临床表现地域差异、诊断标准、病理生理及危险因素进行了阐述,对各种治疗方案和预防措施进行了评价,重点分析了各种方案/措施的缺陷。此外,我们还对PVT对预后的影响这一争议问题进行了探讨,着重考虑了肝移植和未来展望。

Sonography in surveillance for HCC in NAFLD patients

Over the last decade,we have been facing a new aetiology responsible for the development of HCC-the nonalcoholic fatty liver disease(NAFLD).The prevalence of HCC development in this group is higher than that observed in the general population and in non-cirrhotic subjects with other causes of liver disease.Conventional ultrasound(US)is the first-line tool for HCC surveillance,but,in this population,it has a decreased diagnostic accuracy due to several particular features,including obesity and steatosis.Contrast-enhanced ultrasound(CEUS)appeared as a new branch of US due to its ability to depict the vascular architecture of all types of focal lesions(FLs).Nevertheless,CEUS has several limitations besides those inherited from US,which renders this method unreliable as the first-line HCC diagnostic tool and for HCC staging.Artificial intelligence eliminates operator limitations,which has led to an increased sensitivity and specificity of US.However,this approach is still in its early stages and more data are needed.Consequently,the purpose of the current study is to highlight the strengths and limits of US,along with its alternatives to HCC screening in NAFLD population.

When lifestyles sign

Nonalcoholic fatty liver disease(NAFLD)has a global prevalence of 25%,reflecting the global epidemic of obesity and diabetes(1).The onset and development of NAFLD are closely associated with dietary habits and lifestyle;consequently,lifestyle modifications including weight loss,increased physical activity,and dietary changes remain the treatment of choice for NAFLD.Even when drugs to treat non-alcoholic steatohepatitis will be available,lifestyle changes will remain an essential component of the therapeutic plan of these patients.In the last years,a strong association between lifestyle and hepatocellular carcinoma(HCC)has become evident(2-4).In patients with NAFLD,the annual incidence of HCC is 0.44 per 1,000 person/year and almost 50%of cases develops in a non-cirrhotic liver resulting in a diagnosis at an advanced stage with a worse prognosis(1,5).Nonetheless,the high prevalence of NAFLD with the relatively low risk for HCC makes a surveillance program cost-ineffective in non-cirrhotic patients(6).

Transforming one organ into another to overcome challenges in tissue engineering

Tissue engineering(TE)is promising for the regeneration of failed organs.However,immune rejection,shortage of seed cells,and unintegrated blood vessels restrict the development and clinical application of TE.The last factor is the most challenging and intractable.Harnessing the mature blood vessel network in existing dispensable organs could be a powerful approach to effectively overcome the obstacles.After being remodeled to harbor an immunosuppressive and proregenerative niche,these potential target organs can be transformed into other organs with specific physiological functions,compensating the latter's failed native functions.Organ transformation,such as a hepatized spleen,represents an effective and encouraging TE strategy.In this review,we discuss the current development and obstacles of TE and its feasibility and superiority in organ transformation.