Thoracic and Esophageal Procedures, Lung Transplant in Cirrhotic Patients: Safety and Limiting Factors


Study

n

Child–Pugh Class

MELD score

Pulmonary resection

Morbidity

Mortality (operative)

Late outcome

Iwasaki et al. [14]

17

Class A: 4

Class B: 13

N/A

Lobectomies = 11

Pneumnectomies = 3

Wedge = 3

Rate = 29.5%

Respiratory complications: n = 5

(45.5%)

n = 1 (5.9%), class B

Survival: 87.8, 57, 45.6% at 1, 3, 5 year

Hepatic failure related mortality: n = 4

Class B: 30.8% morbidity and 7.6% mortality

Iwata et al. [9]

37

Class A: 28

Class B: 9

N/A

Lobectomies = 32

Wedge = 5

Cirrhosis-related: n = 7 (18.9%)

Transient liver failure: n = 2 (5.4%)

Surgical bleeding: n = 4 (10.8%)

n = 2 (5.4%), due to sepsis

HCC death: n = 1 (2.7%) at 6.5 months

Cirrhotic death: n = 1 (2.7%) at 11.3 months

Lung cancer death: n = 1 (2.7%) at 8.1 months

Iwata et al. [15]

33

Class A: 24

Class B: 9

N/A

≥ Lobectomies = 29

Wedge = 4

Transient liver failure: n = 2 (6.5%)

Surgical bleeding: n = 3 (9.7%)

n = 2 (6.5%)

Lung cancer survival: 84, 65.1, 59.7% at 1, 3, 5 year

Cirrhotic survival: 92.1, 92.1, 62.9% at 1, 3, 5 year

Overall survival: 77.3, 59.9, 37.6% at 1, 3, 5 year

Iwata et al. [16]

11

Class A: 10

Class B: 1

N/A

Lobectomies = 8

Wedge = 3

Liver failure n = 2 (18.2%)

Surgical bleeding n = 2 (18.2%)

n=0

Lung cancer survival: 88.9, 74.1, 74.1%,at 1, 3, 5 year

Cirrhotic survival: 79.5, 79.5, 39.8%, at 1, 3, 5 year

Overall survival: 70.7, 58.9, 29.5%, at 1, 3, 5 year

Rivera et al. [17]

49

N/A

N/A

Lobectomies = 33

Pneumnectomies = 10

Wedge = 5

Explorative thoracotomy = 1

n = 20

40.8% Hepatic vs. 24.8% nonhepatic disease (p = 0.11)

n = 4

8.2% Hepatic vs. 4.2% nonhepatic disease (p = 0.32)

5-year survival: 35.3% Hepatic vs. 43.8% nonhepatic disease (p = 0.0021)



Cirrhotic patients undergoing pulmonary resection experience perioperative complications between 5 and 45% of the time (Table 20.1). The most common complication is postoperative bleeding, either surgical site or less commonly gastrointestinal bleeding. This results in an increased requirement for perioperative blood transfusion [9, 15, 16]. Other complications include acute liver failure (5–18%) and sepsis (5.4%) transfusion [9, 15, 16]. Operative mortality related to liver cirrhosis ranges between 5 and 8% transfusion [9, 15–17].

Iwata et al. reported that 5-year survival was 37.6% in 33 cirrhotic patients who underwent lung cancer surgery [15]. Further analysis has shown that the 5-year survival from lung cancer-related death was lower than 5-year survival from liver disease-related death (59.7% vs. 62.9%, Table 20.1). The authors observed that the most common cause of death in the first three postoperative years was lung cancer, while in the subsequent 3 years, liver disease was the most common cause of death [18]. Iwasaki et al. reported long-term outcomes of lung cancer surgery in 17 patients with liver cirrhosis [14]. The 5-year overall survival was 45.6%. Liver cirrhosis–related mortality was 7.6%, with all mortalities occurring in Child–Pugh class B patients while none was noted among Child–Pugh class A patients. Recently, Rivera et al. reported that the 5-year survival was significantly lower among cirrhotic patients who underwent lung cancer surgery compared to those without liver disease (35.3% vs. 43.8%, p = 0.0021) [17].

Chronic liver dysfunction is associated with impaired clearance of systemic vasodilators leading to a prolonged effect on various tissue beds. In the lung, it causes increased pulmonary vasculature vasodilatation and/or formation of arteriovenous shunting in the tissue bed. Subsequently, mild hypoxemia, hyperventilation, hypocapnia, and decreased diffusion capacity occur [18, 19]. Collectively, hepatic dysfunction, hypoxemia, and intrapulmonary vasodilatation are known as hepatopulmonary syndrome [20]. Portoplumonary hypertension is another unique entity in which liver cirrhosis and portal hypertension lead to pulmonary hypertension, which complicates any pulmonary resection procedure [21]. Cirrhosis contributes to pulmonary dysfunction in other ways too, including atelectasis and poor respiratory mechanics secondary to ascites, and hepatic hydrothorax.

Liver fibrosis is associated with portal venous congestion and splenomegaly, resulting in chronic anemia and thrombocytopenia [18, 19]. Impairment of liver synthetic function results in coagulopathy, which along with thrombocytopenia increases the risk of surgical bleeding. Moreover, cirrhotic patients are at risk of gastrointestinal bleeding (from esophageal or gastric varices or congested gastric mucosa) in the setting of surgical stress. The congestion of Intestinal mucosa interrupts nutrient absorption and, along with impaired albumin synthesis, causes malnutrition and increased susceptibility to infection. Impaired bile acid synthesis affects fat and fat-soluble vitamin absorption, including vitamin K. All of these pathophysiological changes increase the risk of perioperative complications in cirrhotic patients [18, 19].



Gastrointestinal Reflux Disease and Achalasia


The incidence of gastrointestinal reflux disease (GERD) in cirrhotic patients is higher than the general population with a reported incidence of 25–55% [22, 23] and as high as 64% in patients with esophageal varices [24]. If medical treatment fails to control symptoms in these patients, surgery can be considered based with the patient’s Child classification used to predict risk/benefit ratio of Nissen fundoplication (either open or laparoscopic) [25].

Achalasia is uncommon esophageal motility disorder characterized by loss of peristalsis and insufficient lower esophageal sphincter relaxation. Surgical management of this condition is considered if nitrates and calcium channel blockers fail to control symptoms. Coexistence of achalasia and cirrhosis is seldom reported and complicates potential surgical therapy especially if the patient has portal hypertension and esophageal varices [26]. Management of these patients depends first on presence of portal hypertension and esophageal varices and then on their Child’s classification to predict operative risk. If the cirrhotic patient has no signs of portal hypertension or esophageal varices, pneumatic dilation or surgical myotomy may be considered based on Child classification. If the cirrhotic patient has esophageal varices, most authors suggest minimal intervention with botulinum toxin injection [26] or, recently, endoscopic ultrasound-guided botulinum injection to avoid inadvertent laceration of the varices [27].


Esophageal Cancer


Surgery remains the mainstay treatment for early and locally advanced esophageal adenocarcinoma in conjunction with adjuvant or neoadjuvant chemotherapy or chemoradiation [28]. Moreover, salvage esophagectomy is the only curative option if chemo/radiotherapy or chemoradiation fails to control the disease [28]. The incidence of liver cirrhosis in esophageal cancer patients is about 7% [29], with overall morbidity after esophageal surgery in these patients twice that observed in noncirrhotic patients (17–21% vs. 3–8%) [30, 31]. Therefore, with reported unsatisfying results of esophagectomy in these patients, a comprehensive preoperative evaluation including liver function assessment is mandatory along with selection of appropriate procedure and preoperative phase management according to patient evaluation and nutritional status [32].

The incidence of perioperative complications in cirrhotic patents following esophagectomy ranges between 31 and 89% in the published series (Table 20.2). The most common reported complication was ascitic effusion, which is the cause of death in one-third of patients [30, 33, 34], and pneumonia in other series [34]. Other reported complications includes, respiratory failure [35], anastomotic leak, hepatorenal syndrome, portal thrombosis [33], and sepsis [30]. Reported operative blood loss during esophagectomy in cirrhotic patients has been variable. Fekete et al. reported that no massive intraoperative blood loss occurred and attributed that to cautious dissection and hemostasis during surgery [33].


Table 20.2
Published series for esophagectomy in cirrhotic patients



















































































Study
Country
Number of patients
Child classification
Thoracotomy
Postoperative morbidity
Perioperative mortality
Survival

A
B
C

Fekete et al. [33]
France
23
21
2
0
In 20 patients
83%

 Ascites, 65%

 Respiratory failure, 17%

 Anastomotic leak, 13%

 Hepato-renal syndrome, 13%
26%
N/A

Belghiti et al. [30]
France
30
30
0
0
In all patients
89%

 Ascites in 68%

 Sepsis 21%
21%
N/A

Belghiti []
France
53
N/A
N/A
N/A
All patients
72%

 Ascites 26%

 Pleural effusion 26%

 Anastomotic leak 24%

 Infection 22%
26%
N/A

Tachibana et al. [31]
Japan
18
11
7
0
In all patients with three fields LND
83.3%
16.7%
1 year, 50%,

3 years, 21%

Lu et al. [34]
Taiwan
16
10
4
2
In all patients
31.75%

 Pneumonia, 18.75%

 Respiratory failure, 12.5%
25%,

10%, 50%, and 100% in Child A, B, and C, respectively
N/A

Reported perioperative mortality rates are still high in the published series, ranging from 10 to 26%, which is comparable to the mortality rate associated with other gastrointestinal surgeries in cirrhotic patients [36]. It is much higher, however, in Child’s B and C patients, 50%, and 100%, respectively, as reported in one series [37]. Tachibana et al. reported 1- and 3-year survival of 50% and 21%, respectively, in a series of 18 patients [31]. Preoperative predictors of mortality include (1) hepatic functional reserve reflected by Child’s score (Fekete et al. reported an acceptable postoperative mortality rate in patients with Child’s A or selected Child B cases [31] and an unacceptable rate in Child’s B patients with disturbed liver functions and low prothrombin value [33] and in Child’s C patients), (2) presence of acute viral hepatitis [30, 33], and (3) prothrombin time above 160% of normal.

The impact of surgical approach on mortality rate in these patients has been addressed in several publications. Fekete et al. reported no difference in mortality rates between patients who underwent abdominal, thoracic, or a combined approach [33]. Similarly, Ueda et al. suggested that thoracotomy does not add more risk to cirrhotic patients even in advanced disease provided skilled postoperative management is applied [38]. However, Baker et al. reported 2 deaths out of 23 patients with cirrhosis who underwent transhiatal esophagectomy [39].


Thoracic Procedures in Cirrhotic Patients: When to Operate and When Not to Operate?


A number of conditions are associated with unacceptably high risk for elective or semiurgent thoracic procedures including acute or fulminant hepatitis, acute viral hepatitis, acute alcoholic hepatitis, and American Society of Anesthesiologists Physical Status class V [19]. Existing data suggest that elective procedures should not be performed in Child–Pugh class C patients or those with a MELD score >15 [3, 19]. Emergency surgery in patients with cirrhosis carries high risk and poor outcomes compared to elective surgery [19].

The general consensus is that surgery is tolerated in Child–Pugh class A patients or those with a MELD score <10, while it is accepted in Child–Pugh class B or MELD score 10–15 after adequate preoperative optimization [3, 19]. With regard to lung cancer surgery, Iwata suggested that pulmonary resection can be carried out if life expectancy is expected to be more than 3 years based on liver condition [18].



Lung Transplantation in Cirrhotic Patients



Pulmonary Complications in Liver Transplantation Candidates


In liver transplant candidates with cirrhosis, the following pulmonary complications might be encountered: hepatopulmonary syndrome, portopulmonary hypertension, hepatic hydrothorax, advanced chronic obstructive pulmonary disease (COPD), pulmonary nodules, and interstitial lung disease.

Hepatopulmonary syndrome (HPS) is characterized by liver disease, poor oxygenation, and intrapulmonary vascular dilatations. Reduced metabolism of vasodilators in the liver causes pulmonary shunting, resulting in severe hypoxemia (PaO2 < 60 mmHg). Usually, hypoxemia resolves following liver transplantation. Although preoperative hypoxemia is associated with increased mortality [40], HPS is not a contraindication for liver transplantation if other morbidities are not identified [41]. Recently, Iyer et al. reported good outcomes for these patients: 76% 5-year survival of HPS patients with preoperative PaO2 < 50 mmHg [42]. The Model for End-stage Liver Disease (MELD) score for patients with PaO2 < 60 mmHg is upgraded by 10% every 3 months.

Portopulmonary hypertension is defined by the following criteria in patients with portal hypertension: (1) mean pulmonary artery pressure >25 mmHg; (2) pulmonary vascular resistance >240 dyne·s/cm5; or (3) pulmonary capillary wedge pressure <15 mmHg. Although most portopulmonary hypertension patients have cirrhosis, the cause of portopulmonary hypertension remains unclear. The following pathogeneses are hypothesized: humoral substance, including serotonin and interleukin-1, genetic predisposition, and thromboembolism. Proliferative pulmonary angiopathy, including intimal and medial thickening, is the typical pathological finding. Patients with mild to moderate portopulmonary hypertension have good liver transplantation outcomes [43], whereas increased postoperative risk and poor clinical outcomes are associated with severe portopulmonary hypertension (systolic pulmonary artery pressure >60 mmHg) [44]. Portopulmonary hypertension is one of chronic liver diseases, which are not accounted for in the MELD scoring system. A MELD exception is applied if the following improvement is achieved: mean pulmonary artery pressure <35 mmHg and pulmonary vascular resistance <400 dyne·s/cm5. Therefore, in the patients with severe portopulmonary hypertension, combined liver–lung transplantation or liver–heart–lung transplant should be considered.

Xiol et al. reported improvement of hepatic hydrothorax following liver transplantation. Of 29 patients with hepatic hydrothorax, 36% had hydrothorax at 1 month but all had resolved within 3 months. Therefore, hepatic hydrothorax is not a contraindication of liver transplantation [45].

In an analysis of COPD patients (n = 67, 18% of total population) receiving liver transplant, COPD severity was not associated with the risk of death [46]. However, severe COPD might be a contraindication for liver transplant, and such a patient could be a candidate of combined liver–lung transplantation, if the criteria for lung transplant are met.

Although interstitial lung disease may be rare in liver transplant candidates, deciding to perform a liver transplant for these patients requires careful consideration. This is because interstitial lung disease is rapidly progressive, resulting in 20–40% 5-year survival [47]. Liver transplant is contraindicated for patients with severe interstitial lung disease, though combined liver–lung transplantation might be considered.


Combined Liver–Lung Transplantation


Because combined liver–lung transplantation (CLLT) is performed in a limited number of programs for a small population of candidates, there is limited information regarding patient demographics and outcomes. The clinical case series of CLLT are listed in Table 20.3 [48–54]. Originally, the Cambridge group reported heart–lung–liver transplantation [49]. In the United States, Barshes et al. reported 11 cases from the United Network for Organ Sharing (UNOS) database between 1984 and 2004 [50]. Arnon et al. reported 15 cystic fibrosis patients from UNOS database between 1987 and 2008 [52]. Recently, the Leuven group published 10 cases performed between 2000 and 2015 [54].
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Jun 27, 2017 | Posted by in GASTROENTEROLOGY | Comments Off on Thoracic and Esophageal Procedures, Lung Transplant in Cirrhotic Patients: Safety and Limiting Factors

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