Systematic Review
Minimally invasive versus open thymectomy: a systematic review of surgical techniques, patient demographics, and perioperative outcomes Nicholas R. Hess1*, Inderpal S. Sarkaria2*, Arjun Pennathur2, Ryan M. Levy2, Neil A. Christie2, James D. Luketich2 1
University of Pittsburgh School of Medicine, Pittsburgh, PA, USA; 2Department of Cardiothoracic Surgery, University of Pittsburgh Medical
Center, Pittsburgh, PA, USA *These authors contributed equally to this work. Correspondence to: Inderpal S. Sarkaria, MD, FACS. University of Pittsburgh Medical Center - Department of Cardiothoracic Surgery, UPMC Presbyterian-Shadyside 5200 Centre Avenue, Suite 715.27 Pittsburgh, PA 15232, USA. Email: [email protected].
Background: Thymectomy is the mainstay of treatment for thymoma and other anterior mediastinal tumors, and is often utilized in the management of patients with myasthenia gravis (MG). While traditionally approached through a median sternotomy, minimally invasive approaches to thymectomy have increasingly emerged. The present systematic review was conducted to compare perioperative and clinical outcomes following minimally invasive thymectomy (MIT) and open thymectomy (OT). Methods: Articles were obtained through a PubMed literature search. Comparative studies reporting clinical outcomes following MIT and OT were eligible for inclusion. We selected studies with full text availability, written in the English language, published after 2005 and with at least 15 patients in each arm. A descriptive analysis was performed. Results: Twenty studies were included, involving a total of 2,068 patients undergoing either MIT (n=838) or OT (n=1,230). Within individual studies, MIT and OT cohorts were well matched with regards to patient age and gender, but there was considerable variation across studies. Resected thymomas were consistently larger in OT groups, with mean diameter significantly larger in five studies (MIT, 29–52 mm; OT, 31–77 mm). MIT was consistently associated with a lower estimated blood loss (MIT, 20–200 mL; OT, 86–466 mL), chest tube duration (MIT, 1.3–4.1 days; OT, 2.4–5.3 days), and hospital length of stay (MIT, 1–10.6 days; OT, 4–14.6 days). There were no consistent differences in rates of perioperative complications, thymoma recurrence, MG complete stable remission, or 5-year survival. Conclusions: In appropriately selected patients, MIT may reduce blood loss, chest tube duration, and hospital length of stay, with comparable clinical outcomes compared to OT via median sternotomy. Keywords: Thymectomy; transsternal; minimally invasive; outcomes Submitted Oct 20, 2015. Accepted for publication Nov 25, 2015. doi: 10.3978/j.issn.2225-319X.2016.01.01 View this article at: http://dx.doi.org/10.3978/j.issn.2225-319X.2016.01.01
Introduction Thymectomy is most commonly indicated and performed for myasthenia gravis (MG), thymoma, and other anterior mediastinal tumors (1-6). While median sternotomy has long been the accepted standard approach, minimally invasive methods have emerged over recent decades
© Annals of Cardiothoracic Surgery. All rights reserved.
including transcervical, video-assisted thoracoscopic (VATS), and robotic video-assisted thoracoscopic (R-VATS) approaches (7-11). While maintaining safety and surgical veracity remain the first priority, in appropriately selected patients, minimally invasive approaches aim to lower postoperative morbidity and improve post-operative quality
www.annalscts.com
Ann Cardiothorac Surg 2016;5(1):1-9
Hess et al. Minimally invasive vs . open thymectomy
2
of life. However, there remains debate regarding the indications, selection, and outcomes of patients undergoing these procedures versus open resections (12-31). The purpose of this systematic review was to synthesize the current literature comparing minimally invasive thymectomy (MIT) versus open thymectomy (OT) approaches. We sought to identify patient demographics and surgical strategies employed, and describe key perioperative and long-term outcomes associated with each approach. Methods Literature search strategy An electronic search of the PubMed database (http://www. ncbi.nlm.nih.gov/pubmed) was conducted from June 2015 to August 2015, employing English language and fulltext availability restrictions. The following search terms were employed: “thymectomy AND (robot OR robotic)” OR “thymectomy AND thoracoscopic”. Results for these searches were then combined and duplicates were sequentially removed. Eligibility criteria Comparative studies reporting clinical outcomes of patients who underwent MIT and OT were eligible for inclusion. To be included, studies were required to have at least 15 patients in each surgical arm. Data extraction and analysis The listed authors extracted data for this review, and quality of evidence was assessed through examination of the design, analysis and sample size of each study. Relevant data from selected studies were tabulated, sorted by characteristics and outcomes of interest. We then performed a descriptive analysis by evaluating the overall trends in studies comparing MIT versus OT. Results Literature search Literature search of the PubMed database using the proposed filters produced a total of 177 articles suitable for screening. Articles were subsequently evaluated for relevancy to this review topic, with 53 meeting eligibility
© Annals of Cardiothoracic Surgery. All rights reserved.
Records identified through database search (n=198)
Records screeened after duplicates removed (n=177)
Records excluded for not meeting eligibility criteria (n=124)
Full-text articles accessed (n=53)
Full-text articles excluded due to: (I) lack of two study arms (II) insufficient sample size (n=33)
Studies included in qualitative synthesis (n=20)
Figure 1 Flow diagram of literature search and study selection.
criteria. Of these 53 articles, 20 were found to include a comparison of MIT and OT, and have at least 15 subjects in each surgical arm. These 20 studies were included in this review (Figure 1). Patient demographics A total of 2,068 patients were reported in the identified studies, including 838 (40.5%) who underwent MIT and 1,230 (59.5%) who underwent OT procedures. Overall, surgical cohorts within individual studies were well matched, with only one study identifying a statistically younger median age in the MIT group versus the OT group (46 vs. 52 years; P=0.02) (20). There was considerable variation of age and gender across studies. Patient age ranged from a mean 20.5 to a median of 64 years in the MIT groups, and a mean of 25.5 to a mean of 65.4 years in the OT groups. Gender distribution ranged from 18% to 64% male in MIT groups, and 29% to 61% male in OT groups (Table 1). The most common indications for thymectomy in the included studies were thymoma [1,046, (51%)] and/or MG [1,132, (55%)]. Overall, 469 (56%) of MIT patients and 577 (47%) of OT patients had thymoma. Similarly, 430 (51%) of MIT and 702 (57%) of OT patients had MG. Patients with thymoma were selected by either clinical or pathological Masaoka staging, and in one instance, World Health Organization (WHO) pathological staging (19). Patients with MG were selected by either thymoma status or Osserman classification. Two studies included all
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Ann Cardiothorac Surg 2016;5(1):1-9
© Annals of Cardiothoracic Surgery. All rights reserved.
www.annalscts.com
2011
2010
2010
2009
Huang
Odaka
Lin
Meyer
R-VATS- right, left or bilateral
R-VATS: right, 15 [65] or left, 8 [35]
VATS: right, 90 [72] or left 35 [28]
VATS : right, 54 [100]
VATS : right or left
VATS: right, 15 [32] or left, 32 [68]
Minimally invasive approach [%]
MG (Osserman 2-4)
MG
nonthymomatous MG
p-Masaoka stage I, II thymoma
MG
MG
c-Masaoka stage I, II thymoma
thymoma (excluding WHO B3 and C subtypes)
all thymectomy procedures
all thymectomy procedures
MG + p-Masaoka stage I, II thymoma
c-Masaoka stage I, II thymoma
p-Masaoka stage I, II thymoma
VATS: side not specified
VATS: right, 48 [100]
VATS: right, 38 [100]
VATS: right, 16 [73] or left, 6 [27]
VATS – right, 33 [100]
VATS: bilateral, 55 [100]
VATS: right, left, or bilateral
VATS: right, 16 [64] or left, 9 [36]
R-VATS, 2 [3] or VATS, 75 [97]: right, 2 [3] or bilateral 75 [97]
R-VATS: right, 13 [87] or left, 2 [13]
VATS: right, 15 [100]
VATS: side not indicated
VATS: right, left, or bilateral
p-Masaoka stage I, II, VATS: right or left III thymoma
anterior mediastinal mass
p-Masaoka stage I, II thymoma
p-Masaoka stage I,II thymoma
nonthymomatous MG
c-Masaoka stage I, II thymoma
nonthymomatous MG
Study population
73
44
194
22
48
38
22
33
55
18
25
77
15
15
45
76
17
34
23
84
47
22
18
66
59
22
45
186
35
18
29
44
22
34
51
125 137
54
49
47
–
57
64*
48
26
64
27
18
56
Combined: 27 38.2*
39.8 34.4
33.1 30.4
51.9 51.1
36.5 37.3
35.6 37.4
64*
45.8 51.7
52
31
46*#
52*#
47
47
42
46
35
44
52
52
60
57
34
MIT
33
33
32
39
30
29
41
47
37
51
61
34
41
59
52
61
54
52
52
–
OT
Male gender [%]
56.8 50.7
54.2 48.6
55
50.5 51.8
63.1 65.4
53.7 52.4
52.5 50.1
51.9 50.0
20.5 25.5
51.3 50.9
37
MIT
MIT OT
OT
Mean age, years
Case number, n
22 [100]
48 [100]
38 [100]
0 [0]
33 [100]
55 [100]
7 [39]
0 [0]
43 [56]
5 [33]
15 [100]
14 [31]
35 [46]
8 [47]
2 [6]
0 [0]
0 [0]
54 [100]
4 [8]
47 [100]
MIT
84 [100]
47 [100]
22 [100]
0 [0]
66 [100]
59 [100]
4 [18]
0 [0]
96 [52]
6 [17]
18 [100]
9 [31]
14 [32]
4 [18]
1 [3]
0 [0]
0 [0]
73 [100]
5 [11]
194 [100]
OT
Presence of MG, n [%]
0 [0]
44 [100]
0 [0]
OT
6 [27]
4 [8]
0 [0]
22 [100]
2 [6]
11 [20]#
18 [100]
25 [100]
10 [13]
10 [67]
15 [100]
45 [100]
76 [100]
17 [100]
11 [32]
23 [100]
21 [25]
6 [13]
0 [0]
18 [100]
6 [9]
25 [42]#
22 [100]
45 [100]
62 [33]
14 [40]
18 [100]
29 [100]
44 [100]
22 [100]
13 [38]
51 [100]
125 [100] 137 [100]
0 [0]
49 [100]
0 [0]
MIT
Presence of thymoma, n [%]
65#
48#
61*#
36*#
–
–
–
44
–
–
–
–
50
–
–
77#
52#
–
65*
44 45*
45
–
61#
46#
–
–
31
33
34
–
29
30
32
–
54#
43# –
–
OT
–
MIT
Mean thymoma diameter, mm
*, denote data presented as a median value; #, values were reported as statistically significant with P
Minimally invasive versus open thymectomy: a systematic review of surgical techniques, patient demographics, and perioperative outcomes Nicholas R. Hess1*, Inderpal S. Sarkaria2*, Arjun Pennathur2, Ryan M. Levy2, Neil A. Christie2, James D. Luketich2 1
University of Pittsburgh School of Medicine, Pittsburgh, PA, USA; 2Department of Cardiothoracic Surgery, University of Pittsburgh Medical
Center, Pittsburgh, PA, USA *These authors contributed equally to this work. Correspondence to: Inderpal S. Sarkaria, MD, FACS. University of Pittsburgh Medical Center - Department of Cardiothoracic Surgery, UPMC Presbyterian-Shadyside 5200 Centre Avenue, Suite 715.27 Pittsburgh, PA 15232, USA. Email: [email protected].
Background: Thymectomy is the mainstay of treatment for thymoma and other anterior mediastinal tumors, and is often utilized in the management of patients with myasthenia gravis (MG). While traditionally approached through a median sternotomy, minimally invasive approaches to thymectomy have increasingly emerged. The present systematic review was conducted to compare perioperative and clinical outcomes following minimally invasive thymectomy (MIT) and open thymectomy (OT). Methods: Articles were obtained through a PubMed literature search. Comparative studies reporting clinical outcomes following MIT and OT were eligible for inclusion. We selected studies with full text availability, written in the English language, published after 2005 and with at least 15 patients in each arm. A descriptive analysis was performed. Results: Twenty studies were included, involving a total of 2,068 patients undergoing either MIT (n=838) or OT (n=1,230). Within individual studies, MIT and OT cohorts were well matched with regards to patient age and gender, but there was considerable variation across studies. Resected thymomas were consistently larger in OT groups, with mean diameter significantly larger in five studies (MIT, 29–52 mm; OT, 31–77 mm). MIT was consistently associated with a lower estimated blood loss (MIT, 20–200 mL; OT, 86–466 mL), chest tube duration (MIT, 1.3–4.1 days; OT, 2.4–5.3 days), and hospital length of stay (MIT, 1–10.6 days; OT, 4–14.6 days). There were no consistent differences in rates of perioperative complications, thymoma recurrence, MG complete stable remission, or 5-year survival. Conclusions: In appropriately selected patients, MIT may reduce blood loss, chest tube duration, and hospital length of stay, with comparable clinical outcomes compared to OT via median sternotomy. Keywords: Thymectomy; transsternal; minimally invasive; outcomes Submitted Oct 20, 2015. Accepted for publication Nov 25, 2015. doi: 10.3978/j.issn.2225-319X.2016.01.01 View this article at: http://dx.doi.org/10.3978/j.issn.2225-319X.2016.01.01
Introduction Thymectomy is most commonly indicated and performed for myasthenia gravis (MG), thymoma, and other anterior mediastinal tumors (1-6). While median sternotomy has long been the accepted standard approach, minimally invasive methods have emerged over recent decades
© Annals of Cardiothoracic Surgery. All rights reserved.
including transcervical, video-assisted thoracoscopic (VATS), and robotic video-assisted thoracoscopic (R-VATS) approaches (7-11). While maintaining safety and surgical veracity remain the first priority, in appropriately selected patients, minimally invasive approaches aim to lower postoperative morbidity and improve post-operative quality
www.annalscts.com
Ann Cardiothorac Surg 2016;5(1):1-9
Hess et al. Minimally invasive vs . open thymectomy
2
of life. However, there remains debate regarding the indications, selection, and outcomes of patients undergoing these procedures versus open resections (12-31). The purpose of this systematic review was to synthesize the current literature comparing minimally invasive thymectomy (MIT) versus open thymectomy (OT) approaches. We sought to identify patient demographics and surgical strategies employed, and describe key perioperative and long-term outcomes associated with each approach. Methods Literature search strategy An electronic search of the PubMed database (http://www. ncbi.nlm.nih.gov/pubmed) was conducted from June 2015 to August 2015, employing English language and fulltext availability restrictions. The following search terms were employed: “thymectomy AND (robot OR robotic)” OR “thymectomy AND thoracoscopic”. Results for these searches were then combined and duplicates were sequentially removed. Eligibility criteria Comparative studies reporting clinical outcomes of patients who underwent MIT and OT were eligible for inclusion. To be included, studies were required to have at least 15 patients in each surgical arm. Data extraction and analysis The listed authors extracted data for this review, and quality of evidence was assessed through examination of the design, analysis and sample size of each study. Relevant data from selected studies were tabulated, sorted by characteristics and outcomes of interest. We then performed a descriptive analysis by evaluating the overall trends in studies comparing MIT versus OT. Results Literature search Literature search of the PubMed database using the proposed filters produced a total of 177 articles suitable for screening. Articles were subsequently evaluated for relevancy to this review topic, with 53 meeting eligibility
© Annals of Cardiothoracic Surgery. All rights reserved.
Records identified through database search (n=198)
Records screeened after duplicates removed (n=177)
Records excluded for not meeting eligibility criteria (n=124)
Full-text articles accessed (n=53)
Full-text articles excluded due to: (I) lack of two study arms (II) insufficient sample size (n=33)
Studies included in qualitative synthesis (n=20)
Figure 1 Flow diagram of literature search and study selection.
criteria. Of these 53 articles, 20 were found to include a comparison of MIT and OT, and have at least 15 subjects in each surgical arm. These 20 studies were included in this review (Figure 1). Patient demographics A total of 2,068 patients were reported in the identified studies, including 838 (40.5%) who underwent MIT and 1,230 (59.5%) who underwent OT procedures. Overall, surgical cohorts within individual studies were well matched, with only one study identifying a statistically younger median age in the MIT group versus the OT group (46 vs. 52 years; P=0.02) (20). There was considerable variation of age and gender across studies. Patient age ranged from a mean 20.5 to a median of 64 years in the MIT groups, and a mean of 25.5 to a mean of 65.4 years in the OT groups. Gender distribution ranged from 18% to 64% male in MIT groups, and 29% to 61% male in OT groups (Table 1). The most common indications for thymectomy in the included studies were thymoma [1,046, (51%)] and/or MG [1,132, (55%)]. Overall, 469 (56%) of MIT patients and 577 (47%) of OT patients had thymoma. Similarly, 430 (51%) of MIT and 702 (57%) of OT patients had MG. Patients with thymoma were selected by either clinical or pathological Masaoka staging, and in one instance, World Health Organization (WHO) pathological staging (19). Patients with MG were selected by either thymoma status or Osserman classification. Two studies included all
www.annalscts.com
Ann Cardiothorac Surg 2016;5(1):1-9
© Annals of Cardiothoracic Surgery. All rights reserved.
www.annalscts.com
2011
2010
2010
2009
Huang
Odaka
Lin
Meyer
R-VATS- right, left or bilateral
R-VATS: right, 15 [65] or left, 8 [35]
VATS: right, 90 [72] or left 35 [28]
VATS : right, 54 [100]
VATS : right or left
VATS: right, 15 [32] or left, 32 [68]
Minimally invasive approach [%]
MG (Osserman 2-4)
MG
nonthymomatous MG
p-Masaoka stage I, II thymoma
MG
MG
c-Masaoka stage I, II thymoma
thymoma (excluding WHO B3 and C subtypes)
all thymectomy procedures
all thymectomy procedures
MG + p-Masaoka stage I, II thymoma
c-Masaoka stage I, II thymoma
p-Masaoka stage I, II thymoma
VATS: side not specified
VATS: right, 48 [100]
VATS: right, 38 [100]
VATS: right, 16 [73] or left, 6 [27]
VATS – right, 33 [100]
VATS: bilateral, 55 [100]
VATS: right, left, or bilateral
VATS: right, 16 [64] or left, 9 [36]
R-VATS, 2 [3] or VATS, 75 [97]: right, 2 [3] or bilateral 75 [97]
R-VATS: right, 13 [87] or left, 2 [13]
VATS: right, 15 [100]
VATS: side not indicated
VATS: right, left, or bilateral
p-Masaoka stage I, II, VATS: right or left III thymoma
anterior mediastinal mass
p-Masaoka stage I, II thymoma
p-Masaoka stage I,II thymoma
nonthymomatous MG
c-Masaoka stage I, II thymoma
nonthymomatous MG
Study population
73
44
194
22
48
38
22
33
55
18
25
77
15
15
45
76
17
34
23
84
47
22
18
66
59
22
45
186
35
18
29
44
22
34
51
125 137
54
49
47
–
57
64*
48
26
64
27
18
56
Combined: 27 38.2*
39.8 34.4
33.1 30.4
51.9 51.1
36.5 37.3
35.6 37.4
64*
45.8 51.7
52
31
46*#
52*#
47
47
42
46
35
44
52
52
60
57
34
MIT
33
33
32
39
30
29
41
47
37
51
61
34
41
59
52
61
54
52
52
–
OT
Male gender [%]
56.8 50.7
54.2 48.6
55
50.5 51.8
63.1 65.4
53.7 52.4
52.5 50.1
51.9 50.0
20.5 25.5
51.3 50.9
37
MIT
MIT OT
OT
Mean age, years
Case number, n
22 [100]
48 [100]
38 [100]
0 [0]
33 [100]
55 [100]
7 [39]
0 [0]
43 [56]
5 [33]
15 [100]
14 [31]
35 [46]
8 [47]
2 [6]
0 [0]
0 [0]
54 [100]
4 [8]
47 [100]
MIT
84 [100]
47 [100]
22 [100]
0 [0]
66 [100]
59 [100]
4 [18]
0 [0]
96 [52]
6 [17]
18 [100]
9 [31]
14 [32]
4 [18]
1 [3]
0 [0]
0 [0]
73 [100]
5 [11]
194 [100]
OT
Presence of MG, n [%]
0 [0]
44 [100]
0 [0]
OT
6 [27]
4 [8]
0 [0]
22 [100]
2 [6]
11 [20]#
18 [100]
25 [100]
10 [13]
10 [67]
15 [100]
45 [100]
76 [100]
17 [100]
11 [32]
23 [100]
21 [25]
6 [13]
0 [0]
18 [100]
6 [9]
25 [42]#
22 [100]
45 [100]
62 [33]
14 [40]
18 [100]
29 [100]
44 [100]
22 [100]
13 [38]
51 [100]
125 [100] 137 [100]
0 [0]
49 [100]
0 [0]
MIT
Presence of thymoma, n [%]
65#
48#
61*#
36*#
–
–
–
44
–
–
–
–
50
–
–
77#
52#
–
65*
44 45*
45
–
61#
46#
–
–
31
33
34
–
29
30
32
–
54#
43# –
–
OT
–
MIT
Mean thymoma diameter, mm
*, denote data presented as a median value; #, values were reported as statistically significant with P
