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ischemia secondary to atrial brillation–related embolic events after discontinua­tion of anticoagulation for other reasons [49]. In this setting it is important to com­municate with the surgical team the timing for restarting therapeutic anticoagulation as continuing to hold it can put them at further embolic risk [50].
R. N. Kulkarni and M. H. Eslami
Second-Look Operations
In the past, second-look procedures were common, and in certain circumstances even an open-abdomen option was adopted, despite catastrophic complications [51–56]. Intestinal perfusion was typically documented when it was already too late, and gangrenous bowel carried an ominous mortality. Today, efcient hemody­namic and oxygenation markers provide a useful picture of the post-operative course, even though regional perfusion decits or imbalances are harder to detect and, in most circumstances, anticipate potential or imminent troubles. Metabolic acidosis, hypoxia, intramural pneumatosis, and signs of sepsis continue to carry prognostic relevance. If a high level of suspicion for ongoing bowel ischemia remains, imaging methods should be repeated, and further interventions planned.
Nutritional Support
Tolerance of the oral diet may be markedly delayed or insufcient even after success­ful revascularization; notably, if enteral resection was required, thus enteral nutrition could be delivered via a nasogastric or nasoenteric tube. Exceptionally a percutaneous gastrostomy or jejunostomy tube may be placed to facilitate enteral feeding. Short bowel syndrome is a possibility after total small bowel ischemia, and intestinal trans­plantation should be considered depending on the circumstances [57–62].
Treatment Options: Arterial
The choice of treatment option depends on various factors such as patient age, comor­bidities, and the severity of the disease and inuences post-operative care algorithms. Endovascular interventions have been increasingly utilized over the last decade, and they have been shown to be a safe and effective alternative to open surgery [3, 63].
Endovascular Interventions
Percutaneous transluminal angioplasty (PTA): PTA involves the use of a balloon catheter to dilate the stenotic or occluded segment of the mesenteric artery to improve blood ow and relieve ischemia. Angioplasty is typically utilized in con­junction with stenting in patients with chronic mesenteric ischemia.
13 Current Management ofPost-operative Mesenteric Ischemia
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Stenting: Stenting involves the placement of a bare metal (uncovered) or covered stent graft within the mesenteric artery, usually the SMA, to maintain patency and improve blood ow. Stenting may be used in conjunction with PTA or performed primarily. Often times after stenting, a patient will need to be placed on antiplatelet medications to prevent stent thrombosis. The most commonly used antiplatelet agents after vascular stenting are aspirin and P2Y12 receptor inhibitors (such as clopidogrel, ticagrelor, or prasugrel) [64]. P2Y12 receptor inhibitors are often pre­scribed in addition to aspirin and are usually continued for a period of 1–12 months, depending on the type of stent [65]. When patients are newly placed on a P2Y12 inhibitor, they should be monitored closely for signs or symptoms of bleeding.
Common access sites include the brachial or common femoral arteries. They should be closely monitored in the immediate post-operative period for any bleed­ing, hematoma formation, or pseudoaneurysm development. It is extremely impor­tant to have a full pulse/signal exam performed and documented at the end of any endovascular case.
Retrograde open mesenteric stenting (ROMS): When percutaneous stenting has no indication or has failed, an alternative is to access the affected artery through an exploratory laparotomy incision via direct percutaneous access into the distal SMA [46]. Aspirin and/or P2Y12 inhibitors will need to be administered in the post­operative setting.
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Open Surgical Interventions
Thrombectomy and bowel resection, with eventual bypass grafting of the mesen­teric artery, were used during decades. In the era of endovascular rst approach, open arterial proposals deserve much less interest. By the same token, mesenteric venous thrombosis is most often handled with systemic anticoagulation without surgical revascularization. Catheter-directed thrombectomy and thrombolysis could be attempted depending on angiographic ndings [66–68]. Non-occlusive mesen­teric ischemia, as alluded to, is primarily a non-surgical condition, except in circum­stances of late diagnosis, when bowel gangrene already occurred and demands resection.
Post-operative Management: Mesenteric Venous Thrombosis (MVT)
Unlike arterial mesenteric ischemia which is typically considered a surgical emer­gency, symptoms of mesenteric venous thrombosis are often less severe and may develop gradually over time. Treatment is often via anticoagulation alone, although surgical intervention may be necessary in extreme cases. Diagnosis is made by CT scan in 90% of patients, and management depends on the presence or absence of bowel necrosis [67, 68]. Long-term management should be directed toward
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treatment of the underlying cause, and regular follow-up after MVT is essential in evaluating the response to treatment. Up to 25% of patients will experience recur­rent thromboses of the mesenteric circulation within the rst 30days. This rate is lowered to 3% if maintained on therapeutic oral anticoagulation [32, 68].
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26. Kumar S, Kamath PS.Acute superior mesenteric venous thrombosis: one disease or two? Am J Gastroenterol. 2003;98(6):1299–304.
27. Kumar S, Sarr MG, Kamath PS.Mesenteric venous thrombosis. NEJM. 2001;345(23):1683–8.
28. Harnik IG, Brandt LJ.Mesenteric venous thrombosis. Vasc Med. 2010;15(5):407–18.
29. North J, Wollenman O Jr. Venous mesenteric occlusion in the course of migrating thrombo­phlebitis. Surg Gynecol Obstet. 1952;95(6):665–71.
30. Zhang J, Duan Z, Song Q, Luo Y, Xin S, Zhang Q.Acute mesenteric venous thrombosis: a bet­ter outcome achieved through improved imaging techniques and a changed policy of clinical management. Eur J Vasc Endovasc Surg. 2004;28(3):329–34.
31. Abdu RA, Zakhour B, Dallis D. Mesenteric venous thrombosis—1911–1984. Surgery. 1987;101(4):383–8.
32. Amitrano L, Guardascione MA, Scaglione M, Pezzullo L, Sangiuliano N, Armellino MF, et al. Prognostic factors in noncirrhotic patients with splanchnic vein thromboses. Am J Gastroenterol. 2007;102(11):2464–70.
33. Mythen M, Webb A. The role of gut mucosal hypoperfusion in the pathogenesis of post­operative organ dysfunction. Int Care Med. 1994;20:203–9.
34. Chang JB, Stein TA. Mesenteric ischemia: acute and chronic. Ann Vasc Surg. 2003;17(3):323–8.
35. Perko MJ, Just S, Schroeder TV.Importance of diastolic velocities in the detection of celiac and mesenteric artery disease by Duplex ultrasound. J Vasc Surg. 1997;26(2):288–93.
36. Zwolak RM.Can duplex ultrasound replace arteriography in screening for mesenteric isch­emia? Semin Vasc Surg. 1999;12(4):252–60.
37. Meaney J.Non-invasive evaluation of the visceral arteries with magnetic resonance angiogra­phy. Eur Radiol. 1999;9:1267–76.
38. Kolkman JJ, Geelkerken RH. Diagnosis and treatment of chronic mesenteric ischemia: an update. Best Pract Res Clin Gastroenterol. 2017;31(1):49–57.
39. Fleischmann D.Multiple detector-row CT angiography of the renal and mesenteric vessels. Eur J Radiol. 2003;45:S79–87.
40. Horton KM, Fishman EK.Multidetector CT angiography in the diagnosis of mesenteric isch­emia. Radiol Clin N Am. 2007;45(2):275–88.
41. Kurland B, Brandt LJ, Delany HM.Diagnostic tests for intestinal ischemia. Surg Clin N Am. 1992;72(1):85–105.
42. Wiesner W, Khurana B, Ji H, Ros PR. CT of acute bowel ischemia. Radiology. 2003;226(3):635–50.
43. Yağmurdur MC, Ozdemir A, Topaloğlu S, Kilinç K, Ozenç A.Effects of alpha tocopherol and verapamil on liver and small bowel following mesenteric ischemia-reperfusion. Turk J Gastroenterol. 2002;13(1):40–6.
44. Akyıldız HY, Sözüer E, Uzer H, Baykan M, Oz B. The length of necrosis and renal insuf­ciency predict the outcome of acute mesenteric ischemia. Asian J Surg. 2015;38(1):28–32.
45. Acosta S, Nilsson T. Current status on plasma biomarkers for acute mesenteric ischemia. J Thromb Thrombol. 2012;33:355–61.
46. Wyers MC.Acute mesenteric ischemia: diagnostic approach and surgical treatment. Semin Vasc Surg. 2010;23(1):9–20.
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47. Saoleas, Moulakakis, Papavassiliou, Kontzoglou, Kostakis. Acute mesenteric ischaemia, a highly lethal disease with a devastating outcome. Vasa. 2006;35(2):106–11.
48. Kozuch P, Brandt L.Diagnosis and management of mesenteric ischaemia with an emphasis on pharmacotherapy. Aliment Pharmacol Ther. 2005;21(3):201–15.
49. Endean ED, Barnes SL, Kwolek CJ, Minion DJ, Schwarcz TH, Mentzer RM Jr. Surgical man­agement of thrombotic acute intestinal ischemia. Ann Surg. 2001;233(6):801.
50. Lange H, Jäckel R. Usefulness of plasma lactate concentration in the diagnosis of acute abdominal disease. Eur J Surg. 1994;160(6–7):381–4.
51. Meng X, Liu L, Jiang H.Indications and procedures for second-look surgery in acute mesen­teric ischemia. Surg Today. 2010;40:700–5.
52. Boley S, Feinstein F, Sammartano R, Brandt L, Sprayregen S.New concepts in the manage­ment of emboli of the superior mesenteric artery. Surg Gynecol Obstet. 1981;153(4):561–9.
53. Lindblad B, Håkansson H. The rationale for “second-look operation” in mesenteric ves­sel occlusion with uncertain intestinal viability at primary surgery. Acta Chir Scand. 1987;153(9):531–3.
54. Shaw R.The “second look” after superior mesenterial embolectomy or reconstruction for mes­enteric infarction. Curr Surg Manag. 1965;509.
55. Tola M, Portoghese A, Maniga A.Laparoscopic second-look in acute intestinal ischemia. Minerva Chir. 1997;52(5):527–30.
56. Kaminsky O, Yampolski I, Aranovich D, Gnessin E, Greif F.Does a second-look operation improve survival in patients with peritonitis due to acute mesenteric ischemia? A 5-year retro­spective experience. World J Surg. 2005;29:645–8.
57. Cheatham ML, Safcsak K, Brzezinski SJ, Lube MW.Nitrogen balance, protein loss, and the open abdomen. Crit Care Med. 2007;35(1):127–31.
58. Friese RS.The open abdomen: denitions, management principles, and nutrition support con­siderations. Nutr Clin Pract. 2012;27(4):492–8.
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60. Lewis SJ, Andersen HK, Thomas S.Early enteral nutrition within 24 h of intestinal surgery versus later commencement of feeding: a systematic review and meta-analysis. J Gastrointest Surg. 2009;13:569–75.
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62. Sagar S, Harland P, Shields R. Early postoperative feeding with elemental diet. Br Med J. 1979;1(6159):293–5.
63. Block TA, Acosta S, Björck M.Endovascular and open surgery for acute occlusion of the superior mesenteric artery. J Vasc Surg. 2010;52(4):959–66.
64. Giustino G, Baber U, Sartori S, Mehran R, Mastoris I, Kini AS, etal. Duration of dual anti­platelet therapy after drug-eluting stent implantation: a systematic review and meta-analysis of randomized controlled trials. J Am Coll Cardiol. 2015;65(13):1298–310.
65. Wyers MC, Powell RJ, Nolan BW, Cronenwett JL. Retrograde mesenteric stenting during laparotomy for acute occlusive mesenteric ischemia. J Vasc Surg. 2007;45(2):269–75.
66. Singal AK, Kamath PS, Tefferi A. Mesenteric venous thrombosis. Mayo Clin Proc. 2013;88(3):285–94.
67. Dentali F, Ageno W, Witt D, Malato A, Clark N, Garcia D, etal. Natural history of mes­enteric venous thrombosis in patients treated with vitamin K antagonists. Thromb Haemost. 2009;102(09):501–4.
68. Hollingshead M, Burke CT, Mauro MA, Weeks SM, Dixon RG, Jaques PF.Transcatheter thrombolytic therapy for acute mesenteric and portal vein thrombosis. J Vasc Interv Radiol. 2005;16(5):651–61.
R. N. Kulkarni and M. H. Eslami
Chapter 14
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Safety andSuccess inModern Liver Transplantation
MadelynnZhang, NavdeepSingh, WilliamK.Washburn, andAustinD.Schenk
Abbreviations
ARDS Acute respiratory distress syndrome BD Brain dead CIT Cold ischemic time CMV Cytomegalovirus CRRT Continuous renal replacement therapy DAA Direct-acting antiretroviral DCD Deceased from cardiac death DILI Drug-induced liver injury EAD Early allograft dysfunction EBV Epstein-Barr virus ESLD End-stage liver disease HAT Hepatic arterial thrombosis HCC Hepatocellular carcinoma HCV Hepatitis C virus HIV Human immunodeciency virus HPS Hepatopulmonary syndrome HSV Herpes simplex virus IC Ischemic cholangiopathy LDLT Living donor liver transplant MARS Molecular adsorbent recirculation system MELD Model for end-stage liver disease
M. Zhang The Ohio State University College of Medicine, Columbus, OH, USA e-mail: madelynn.zhang@osumc.edu
N. Singh · W. K. Washburn · A. D. Schenk ( Department of Surgery, Division of Transplantation, The Ohio State University Wexner Medical Center, Columbus, OH, USA e-mail: navdeep.singh@osumc.edu; ken.washburn@osumc.edu; austin.schenk@osumc.edu
Switzerland AG 2024 J. Faintuch, S. Faintuch (eds.), Recent Strategies in High Risk Surgery,
https://doi.org/10.1007/978-3-031-56270-9_14
*)
219© The Author(s), under exclusive license to Springer Nature
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M. Zhang et al.
NASH Non-alcoholic steatohepatitis PBC Primary biliary cirrhosis PNF Primary non-function POPH Portopulmonary hypertension PSC Primary sclerosing cholangitis SIRS Systemic inammatory response syndrome SMV Superior mesenteric vein SRTR Scientic Registry of Transplant Recipients TPA Tissue plasminogen activator
Introduction
In the six decades since Dr. Thomas Starzl performed the world’s rst successful liver transplant [1], signicant improvements in surgical technique, anesthetic prac­tice, and critical care have allowed liver transplantation to become standard-of-care treatment for patients with end-stage liver disease (ESLD). Without doubt, liver transplantation remains one of the most complex and high-risk abdominal surgical procedures performed. This chapter is intended to provide a practical overview of adult liver transplantation with emphasis on modern strategies employed to mitigate risk and achieve ideal recipient outcomes.
Indications forLiver Transplantation
The Scientic Registry of Transplant Recipients (SRTR) groups the indications for liver transplantation into the 10 categories shown in Table14.1 [2]. As of 2021,
33.9% of patients awaiting liver transplantation carried the diagnosis of alcoholic
liver disease [3]. Non-alcoholic steatohepatitis (NASH) is the second most common indication for liver transplantation comprising 19.2% of the waiting list, and notably
Table 14.1 Potential indications for liver transplantation
Non-alcoholic steatohepatitis (NASH) Alcoholic liver disease Hepatitis B or C Cholestatic liver disease Autoimmune liver disease Metabolic liver disease Malignant liver disease Liver graft failure Acute liver failure Other modalities of acute or chronic liver failure
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this number has increased by 250% over the last 10years. Hepatitis C (HCV) was historically a leading indication for liver transplantation, and a common cause of early graft failure sometimes necessitating re-transplantation [4]. The advent of direct-acting antiretroviral (DAA) medications has greatly reduced the prevalence of HCV, need for HCV-related liver transplantation, and has even allowed for expan­sion of the donor pool wherein HCV-positive donor livers can be transplanted fol­lowed by recipient treatment with DAAs, allowing for excellent long-term outcomes [5, 6].
The category of cholestatic liver diseases includes primary biliary cirrhosis (PBC), primary sclerosing cholangitis (PSC), IgG4-related sclerosing cholangitis, and genetic diseases such as Caroli’s disease that lead to progressive cholestasis. Not infrequently there are mixed disorders in which autoimmune and cholestatic etiologies intersect. Liver transplantation for metabolic diseases is far more com­mon in the pediatric population; however, patients with alpha-1-antitrypsin de­ciency, hemochromatosis, and Wilson’s disease are often transplanted in adulthood. Hepatocellular carcinoma (HCC) is by far the most common malignancy treated with liver transplantation; however, the eld of transplant oncology is rapidly evolv­ing [7] to include intrahepatic and hilar cholangiocarcinoma, colon cancer with unresectable liver metastases, and neuroendocrine tumors [8]. Common causes of acute liver failure include acetaminophen overdose and other forms of drug-induced liver injury (DILI), acute alcoholic hepatitis, viral etiologies, and acute Budd-Chiari syndrome.
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Preoperative Evaluation forLiver Transplantation
Liver transplantation provides full cure for appropriately chosen recipients, but also it has potential to shorten overall length of life when offered to unsuitable candi­dates [9, 10].
Evaluation typically begins with an electrocardiogram, echocardiogram, stress test, and assessment of cardiac risk factors. Risk factors for coronary artery dis­ease including tobacco use, peripheral vascular disease, diabetes, hypertension, hyperlipidemia, and obesity are considered, and left heart catheterization is gener­ally pursued in patients with multiple risk factors. Right heart catheterization is warranted in any candidate with elevated right ventricular systolic pressures or other suggestions of possible right heart dysfunction, and the combination of echocardiography and right heart catheterization are generally used to identify and distinguish between hepatopulmonary syndrome (HPS) and portopulmonary hypertension (POPH). Arterial blood gases should be obtained in all candidates, and formal pulmonary function testing should be pursued in patients with abnor­mal blood gases, a baseline oxygen requirement, signicant exercise-induced desaturation, and smoking history or radiographic evidence of obstructive pulmo­nary disease.
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Two-dimensional liver imaging (CT or MRI) is recommended for all poten­tial candidates and serves dual purposes. Because cirrhosis increases risk for hepatocellular carcinoma, preoperative imaging is used to identify, stage, and plan bridging therapies for candidates with HCC.From a surgical perspective, preoperative imaging allows the transplant surgeon to verify portal vein patency or select alternative inflow, decipher hepatic arterial anatomy, and measure the dimensions of the right upper quadrant in order to select an appro­priately sized donor. In cases of acute or decompensated cirrhosis where can­didates are unstable for transport to radiology, a bedside Doppler ultrasound can substitute.
M. Zhang et al.
Oncology Screening
Upper endoscopy is generally performed to treat esophageal varices prior to wait­listing. Searching for occult malignancies is warranted as these lesions will blossom with the initiation of immunosuppression, and thus colonoscopy should also be per­formed for all candidates over the age of 50 or with increased risk factors for colon cancer. Likewise guidelines for other age-related cancer screenings are followed including mammograms in all female candidates over the age of 40, Papanicolaou (PAP) smear testing in women without hysterectomy, and prostate specic antigen (PSA) testing in men. Alfa fetoprotein levels are also checked in all candidates as an additional screen for HCC.
Several additional components round out the pretransplant work-up. Dental screening is recommended, and critical dental issues should be addressed pretrans­plant. Formal or informal clinical frailty assessment is absolutely essential to iden­tify candidates who can complete the rigorous recovery that follows liver transplantation [11]. Psychiatric and neurocognitive testing can be useful to assess readiness for transplant in cases of addictive disease (e.g. alcohol or drug-related HCV) and to ensure medication adherence and baseline stability in cases of comor­bid psychiatric disease (e.g. schizophrenia, bipolar disease).
Transplant centers generally verify the willingness of at-home support resources for transplant candidates, particularly in cases where physical or mental barriers decrease recipient independence and necessitate intensive care-giving. Financial and insurance assessments help verify transplant center reimbursement and also ensure that transplant-related costs will not be bankrupting for the recipient. Lastly, preoperative bloodwork is used to calculate model for end-stage liver dis­ease (MELD) score, assess renal function, measure cytomegalovirus (CMV), Epstein- Barr virus (EBV), and herpes simplex virus (HSV) serostatus, and exclude syphilis, active hepatitis, human immunodeciency virus (HIV) and tuberculosis. Most programs also include drug and alcohol screening in candidate bloodwork (Table14.2).
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223
Table 14.2
for liver transplantation
Essential evaluation
Cardiovascular screening Electrocardiogram Echocardiogram Stress test Right and left heart catheterization (if indicated) Pulmonary testing Chest X-ray Arterial blood gas Pulmonary function tests Liver imaging (CT, MRI, or Doppler US) Frailty assessment Upper gastrointestinal endoscopy Age and gender appropriate cancer screening Dental screening Psychiatric and neurocognitive assessment Verication of at-home support Financial and insurance assessment Bloodwork
CT Computed tomography, MRI Magnetic resonance imaging, US Ultrasonography
Absolute Contraindications toLiver Transplantation
Flow-limiting coronary artery disease not amenable to percutaneous or open surgi­cal intervention is a rare but absolute contraindication to liver transplantation. Likewise, non-correctable severe valvular disease and conditions causing signi­cant non-reversible depression of the ejection fraction prohibit transplantation. Due to the proximity and “in-series” relationship of the liver and right ventricle, dynamic right heart function is essential for safe liver transplantation. Regardless of etiology, non-correctable conditions causing a mean pulmonary artery pressure >40mmHg are generally considered an absolute contraindication [12]. Extra-hepatic malig­nancy is almost always a contraindication to liver transplantation, as are uncon­trolled psychiatric illness, lack of adequate social support, and inability to pay for post-transplant medications.
Relative Contraindications toLiver Transplantation
There is no recommended maximum age for liver transplant recipients, and cer­tainly transplant recipients in their seventies and even eighties can experience excel­lent outcomes [13, 14]. Rather, age must be considered in the context of functional
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