Thoracoscopic Segmentectomy for Lung Cancer

Thoracoscopic Segmentectomy for Lung Cancer

REVIEW Thoracoscopic Segmentectomy for Lung Cancer Chi-Fu Jeffrey Yang, MD, and Thomas A. D’Amico, MD Department of Surgery, Duke University Medical ...

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REVIEW

Thoracoscopic Segmentectomy for Lung Cancer Chi-Fu Jeffrey Yang, MD, and Thomas A. D’Amico, MD Department of Surgery, Duke University Medical Center, Durham, North Carolina

REVIEW

Lobectomy has long been considered the standard procedure for early-stage lung cancer, and minimally invasive techniques have been demonstrated to be associated with superior outcomes compared with lobectomy by thoracotomy. The use of segmentectomy is under investigation for selected patients with small tumors, and the use of minimally invasive strategies is applicable as well. In this review, we analyzed studies that have compared (1) thoracoscopic segmentectomy versus the open approach, (2) thoracoscopic segmentectomy versus thoracoscopic lobectomy, and (3) thoracoscopic segmentectomy versus thoracoscopic lobectomy versus thoracoscopic

wedge resection. When compared with open segmentectomy, preliminarily, thoracoscopic segmentectomy was found to have equivalent oncologic results, with shorter hospital length of stay, reduced rates of morbidity, and lower cost. When compared with thoracoscopic lobectomy, thoracoscopic segmentectomy had equivalent rates of morbidity, recurrence, and survival. Preliminarily, thoracoscopic segmentectomy was found to result in greater preservation of lung function and exercise capacity than the thoracoscopic lobectomy. (Ann Thorac Surg 2012;94:668 – 81) © 2012 by The Society of Thoracic Surgeons

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than 2 cm, especially in patients with marginal cardiopulmonary function. In addition, there is now a better understanding of the potential advantages of the thoracoscopic segmentectomy—the video-assisted thoracoscopic surgery (VATS) approach—for anatomic pulmonary resection [12–17]. The definition of thoracoscopic segmentectomy is the completion of sublobar anatomic pulmonary resection, with individual vessel ligation and without the use of a utility thoracotomy, retractors, or rib spreading [12, 15]. There are also numerous reports of “video-assisted” segmentectomy, or “hybrid” segmentectomy, but these techniques fall into the category of open surgery. Large propensity-matched studies [13, 14] and a recent systematic review of the literature [16] demonstrated that the thoracoscopic approach to lobectomy is associated with reduced chest tube duration, shorter length of hospital stay, and fewer postoperative complications. Similarly, it is hypothesized that the thoracoscopic approach to segmentectomy may have benefits over an open approach [12, 15]. The concept of thoracoscopic segmentectomy for lung cancer raises several controversial issues. The first— regarding the role of segmentectomy as opposed to lobectomy for early-stage lung cancer—will become increasingly important as CT screening for lung cancer becomes more prevalent. The second consideration relates to the issue of whether the numerous advantages of the thoracoscopic approach to lobectomy are also relevant to thoracoscopic segmentectomy. Finally, there are technical challenges of thoracoscopic segmentectomy, which may reflect on the appropriateness of the minimally invasive strategy. We reviewed the available published evidence relating to thoracoscopic segmentectomy for lung cancer in an effort to resolve the uncertainty regarding the efficacy and outcomes compared with open segmentectomy and thoracoscopic lobectomy.

n 1939, Churchill and Belsey [1] first described pulmonary segmentectomy for the treatment of bronchiectasis, performing lingulectomy in 86 patients. In the following decades, thoracic surgeons began applying segmentectomy to patients with primary lung cancers [2, 3]. However, in 1995, the Lung Cancer Study Group led by Ginsberg and colleagues [4] performed a randomized controlled trial demonstrating that limited pulmonary resection for tumors smaller than 3 cm resulted in increased locoregional recurrences compared with lobectomy. Subsequently in North America, segmentectomy has generally been restricted to patients with marginal cardiopulmonary function [5]. In a review from the Society of Thoracic Surgeons General Thoracic Surgery Database, segmentectomy is performed in only 4.4% of pulmonary resections [6]. However, interest in segmentectomy for small tumors has recently increased. Since 1995, newer imaging modalities and enhanced computed tomography (CT) screening protocols have identified increasing numbers of smaller lung tumors (1–2 cm) in higher risk surgical patients [7–9]. The effect of lobectomy versus segmentectomy on these very small tumors was not specifically assessed by the study performed by Ginsberg and colleagues [4] in which 30% of patients had tumors that were larger than 2 cm. In addition, since 1995 newer staging modalities have emerged that likely improve patient selection for anatomic lung resection, such as combined positron-emission tomography (PET) and computed tomography (PET-CT), transesophageal ultrasonographically guided fine-needle aspiration, or endobronchial ultrasonographically guided transbronchial needle aspiration [10, 11]. As a result, segmentectomy is being proposed for carefully selected patients with tumors less

Address correspondence to Dr D’Amico, Department of Surgery, Duke University Medical Center, Box 3496, Duke S, White Zone, Room 3589, Durham, NC, 27710; e-mail: [email protected].

© 2012 by The Society of Thoracic Surgeons Published by Elsevier Inc

0003-4975/$36.00 http://dx.doi.org/10.1016/j.athoracsur.2012.03.080

Material and Methods To identify relevant articles for inclusion in our analysis, we performed a literature review of the MEDLINE database. We searched for randomized controlled trials, observational studies, and case series that evaluated thoracoscopic segmentectomy, thoracoscopic segmentectomy versus open segmentectomy, thoracoscopic segmentectomy versus thoracoscopic wedge resection, and thoracoscopic segmentectomy versus thoracoscopic lobectomy for non-small cell lung cancer (NSCLC) (Table 1). The studies contained data on operative variables, complication rates, length of hospital stay, or survival rates of patients who underwent either thoracoscopic or open segmentectomy (Tables 2– 6).

Feasibility of Thoracoscopic (Video-Assisted Thoracoscopic Surgery) Segmentectomy The development of thoracoscopic (video-assisted thoracoscopic surgery [VATS]) segmentectomy followed in North America and Asia after the demonstration of the safety and feasibility of VATS lobectomy [17]. In 2004, Houck and colleagues [18] reported a series of 11 patients with lung cancer who underwent 1 specific segmentectomy procedure: left upper lobe apical trisegmentectomy. In this series, 7 patients had stage IA disease, 2 patients had stage IB disease, 1 patient had stage IIA disease, and 1 patient had stage IIIA disease. Tumor size was 2.36 ⫾ 0.60 cm. There was no operative mortality, no need for blood transfusions, no conversions to thoracotomy, and no evidence of recurrence at 13.5 months. The mean length of stay was 4.3 ⫾ 3.1 days. In 2009, Watanabe and colleagues [19] reported a series of 41 patients with radiographically staged T1N0M0 (T ⬍ 2 cm) NSCLC who underwent VATS segmentectomy. Mean operative time was 220 ⫾ 56 minutes. The 5-year overall survival and recurrence-free survival rates in pathologic stage IA NSCLC were 89.9% and 93.3%, respectively. In 2011, Dylewski and colleagues [20] reported a series of 200 consecutive patients who underwent robotic thoracoscopic operations. Of these, 35 patients underwent robotic thoracoscopic segmentectomy for lung disease, including 12 patients who had stage IA NSCLC. In this series, median age was 66.5 years [21]. Median tumor size was 1.4 cm. Median operating room time was 146 minutes (range 82–229 minutes). Four of the 35 patients had perioperative complications, and 60-day mortality was 0%. The median length of hospital stay was 2 days (range 1–15 days).

Thoracoscopic Segmentectomy Versus Open Segmentectomy In 2004, Shiraishi and colleagues [22] performed a retrospective study of 34 patients who underwent VATS segmentectomy versus 25 patients who underwent a thoracotomy approach. The authors selected patients with clinical stage IA peripheral tumors less than 2 cm in

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diameter. The procedures were classified as either “intentional” or “compromised.” In the intentional group (n ⫽ 22), patients underwent VATS segmentectomy with systemic lobar and mediastinal lymph node dissection with curative intent. In the compromised group, patients were selected for VATS segmentectomy because they were not candidates for lobectomy because of marginal cardiopulmonary reserve or multiple comorbidities. Operative time was significantly longer by approximately 37 minutes in the VATS group. There were no differences in blood loss. The hospital length of stay was significantly reduced in the VATS group by approximately 4 days. There were no differences in postoperative complications and number of patients with prolonged air leaks greater than 7 days. Perioperative and 30-day mortality was 0% in both the compromised and intentional group. In 2007, Atkins and colleagues [12] performed a retrospective review of 48 patients who underwent VATS segmentectomy versus 29 patients who underwent a thoracotomy approach. Of these patients, 39 operations were for primary lung cancer. The VATS and thoracotomy groups were well matched for age, percentage of male sex, total pack-years of tobacco exposure, and previous thoracic procedures. The groups also had similar pulmonary function as measured by forced expiratory volume in 1 second (FEV1) and lung diffusion capacity for carbon monoxide. Operative time, estimated blood loss, nodal stations sampled, and duration of chest tube use were similar between the 2 groups. Locoregional recurrences were also similar between the open (8.3%) and the VATS (7.7%) approach. However, hospital length of stay was significantly less among patients undergoing VATS (4.3 ⫾ 3 days versus 6.8 ⫾ 6 days; p ⫽ 0.03). Thirty-day mortality was 6.9% (2 of 29 patients) for the thoracotomy group compared with 0% for the VATS group. Follow-up was for approximately 30 months, with patients in the VATS group having improved long-term survival (p ⫽ 0.0007). Schuchert and colleagues conducted a retrospective study comparing the results of 104 patients who underwent VATS versus 121 patients who underwent a thoracotomy approach [23]. The 2 groups were well matched for age, sex, histologic stage (all were stage IA or IB NSCLC), and pulmonary function as measured by FEV1 and lung diffusion capacity for carbon monoxide. The thoracotomy group had slightly larger tumor size than the VATS group (2.4 ⫾ 1.2 cm versus 2.1 ⫾ 1.1 cm; p ⫽ 0.05). Segmentectomies in both right and left upper and lower lobes were performed. Operative time and estimated blood loss were similar between the 2 groups. The 30-day mortality in patients undergoing the VATS approach was 0% and 1.7%, respectively, with the open approach. Median hospital length of stay was significantly less among patients undergoing VATS (5 versus 7 days; p ⬍ 0.001). Regarding postoperative morbidity, there were significantly fewer perioperative pulmonary complications in the VATS group (15.4% versus 29.8%; p ⫽ 0.012). In addition, there was a trend toward fewer infections in the VATS group (3% to 10%; p ⫽ 0.13). The VATS and open groups had similar rates of postoperative

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Table 1. Study Characteristics Patient No.

Age, y

2004 2004

11 34

Iwasaki

2004

Oizumi

Lead Author

a

Adenocarcinoma, %a

Squamous Cell Carcinoma, %a

F

M

70 ⫾ 10 69 ⫾ 10

8 18

3 16

82 65

18 29

40

...

...

...

...

...

2009

30

67 (16–81)

18

12

5

10

80

Atkins

2007

48

62 ⫾ 13

24

24

33

11

4

Watanabe

2009

41

63 ⫾ 12

15

26

24

15

49

Shapiro

2009

31

65 ⫾ 9.5

23

8

Schuchert

2009

104

70 ⫾ 8

49

55

55

28

1

Leshnower

2010

15

65 ⫾ 11

7

8

20

33

13

VATS Segmentectomy Houck Shiraishi

61.3

9.7

Type of Operation/Notes

0

LUL trisegmentectomy L upper division (6), L lingular division (4), basal division segmentectomy (16) Types of segmentectomies not specified. Dissection of hilar and mediastinal lymph nodes was performed. Right lung: S1 (3), S2 (3), S2 ⫹ 3a (1), S3 (2), S3 ⫹ 1b(1), S6(2), S8 (1), S8 ⫹ S9 (1), S9 ⫹ 10 (1) Left lung: S1 ⫹ 2 (1), S1 ⫹ 2 ⫹ 3 (5), S1 ⫹ 2 ⫹ 3 ⫹ 6 (1), S3 ⫹ S4 (1), S4 ⫹ 5 (1), S8 (3), S8 ⫹ 9 ⫹ 10 (3) Superior (12/48), basilar (14/48), lingulectomy (7/48), apical (3/48), lingula-sparing upper lobectomy (12/48) Cervical mediastinoscopy was performed in 18/48 patients Mediastinal lymph node dissection was performed in 40/48 patients; 44 had malignant disease Right lung: S1 (2), S2 (2), S3 (2) S6 (3), S6 ⫹ S9 ⫹ S10 (8), S9 ⫹ S10 (5), S7–S10 (9), RUL ⫹ S6 (13) Left lung: S1 ⫹S 2 (3), LUD (6), LLD (4), LLD ⫹ S3 (7), LLD ⫹ S6 (7), LUL ⫹ S6 (13), S6 (3), S8 ⫹ S9⫹S10 (7) Lingulectomy (2/31), LLL superior (3/31), lingula–sparing upper lobectomy (17/31), RLL superior (7/31), LLL composite basilar (1/31), RLL composite basilar (1/31). RUL anterior (4), RUL posterior (11), RUL apical (5), RUL apicoposterior (2), RML (14), RLL superior (10), RLL basilar (9), LUL upper division (24), LUL lingula (14), LLL superior (4), LLL basilar (10) RUL posterior (2), RUL apical (2), RLL superior (2), RLL medial basilar (2), LUL apical posterior (1), LUL lingula (1), LLL superior (4), LLL anteromedial (3)

b

b

b

(Continued)

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BAC (%)

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Gender

Year Published

Gender

Patient No.

Age, ya

F

M

Adenocarcinoma, %a

Squamous Cell Carcinoma, %a

BAC (%)

Type of Operation/Notes

Sugi

2010

43

62 ⫾ 9

24

19

37

5

53

Gossot

2011

50

57

25

25

72

8

b

Nakamura Yamashita

2011 2011

38 38

72.6 72

21 16

17 22

87 26

10 18

b

45

Moroga

2011

20

67 (54–80)

12

8

6

1

13

Moroga

2011

63

70 (31–87)

31

32

18

10

30

Dylewski

2011

35

66.5

17

18

25

14

b

Yamashita

2012

90

69 (31–87)

49

41

29

12

53

Specific details of segmentectomies not included Procedures included superior major portion segmentectomy, lingulectomy, S6 segmentectomy and basal segmentectomy More localized procedures of segmentectomy, such as S1 ⫹ 2 and S8 segmentectomy, were not performed R apicosuperior (9), R superior (6), R basilar (7), lingula-sparing L upper lobectomy (7), L apicosuperior (4), lingula (4), L superior (6), and L basilar (7) 20 radical lymphadenectomies were performed Only 25 cases were NSCLC. Types of segmentectomies not specified RUL: S1 (2), S2 (3), S3 (1), S2 ⫹ 3a (1), RLL: S6(4), S7 ⫹ 8 (2), S8 (1), S9 ⫹ 10 (1), Basilar (2). LUL: S1 ⫹ 2 (3), S3 (1), upper division (5) Lingula (2), LLL, S6 (5), S8 (1), S9 (1), basilar (3) Performed with sentinel lymph node biopsy Performed without sentinel lymph node biopsy R apical posterior segment (7), R lower superior segment (2), R lower basilar segment (6), L apical posterior segment (4), lingula (5), L lower superior segment (4), L lower basilar segment (7) RUL: S1 (6), S1 ⫹ 2 (1), S1a ⫹ 2 (1), S2 (6), S2 ⫹ 3a (2), S2,6 (1), S3 (7), S3, 10 (1), S3,4 ⫹ 5a (1) RLL: S6 (9), S6 ⫹ 10 (1), S7 ⫹ 8 (2), S8 (2), S8 ⫹ 9 (1), S9 ⫹ 10 (2), basilar (3) LUL: S1 ⫹ 2 (3), S3(2), S4(1), upper division (15), upper division ⫹ S4 (1), lingula (2), lingula, S6 (1) LLL: S6 (7), S6 ⫹ 9 (1), S8 (3), S8 ⫹ 9 (2), S9 ⫹ 10 (1), basilar (5)

Lead Author

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Year Published

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Table 1. Continued

(Continued)

671

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Table 1. Continued

Age, ya

F

M

Adenocarcinoma, %a

Squamous Cell Carcinoma, %a

2004

100

...

...

...

...

...

Atkins

2007

29

59 ⫾ 13

13

16

20

18

0

Schuchert

2009

121

70 ⫾ 10

66

55

57

32

2

Leshnower

2010

26

64 ⫾ 15

10

61

...

...

b

Shiraishi

2004

25

72 ⫾ 7

...

...

...

...

b

2009 2010

113 95

69 ⫾ 11 65 ⫾ 9

59 64

54 31

78 29

15 8

b

2011 2011 2012

289 71 124

67.7 68 68 (50–90)

146 27 51

143 44 73

90 63 51

9 13 20

b

21 52

2009

21

62.5

8

13

10

...

90

2011

84

74.9

26

58

63

33

b

Thoracotomy Segmentectomy Iwasaki

VATS Lobectomy Shapiro Sugi Nakamura Yamashita Yamashita VATS Wedge Resection Sugi

Nakamura

b

Type of Operation/Notes

b

VATS lobectomy with dissection of hilar and mediastinal lymph nodes Superior (16/48), basilar (5/48), lingulectomy (4/48), apical (3/48), lingula-sparing upper lobectomy (1/48) Cervical mediastinoscopy was performed in 8/48 patients Mediastinal lymph node dissection was performed in 24/48 patients RUL anterior (7), RUL posterior (17), RUL apical (8), RUL apicoposterior (10), RML (10), RLL superior (13), RLL basilar (10), LUL upper division (26), LUL lingula (5), LLL superior (10), LLL basilar (5) RUL posterior (6), RUL anterior (1), RLL superior (3), RLL medial basilar (1), RLL extended basilar (1), LUL apical posterior (2), LUL anterior (1), lingula (2), LLL superior (6), LLL anteromedial (1), LLL composite basilar (2) Segmentectomies not described

b

Lobectomies not described Lobectomies performed on tumors in the R upper and middle lobes Lobectomies not described RUL, 24, RML, 8, RLL, 15, LUL, 11, LLL, 13 Lobectomies not described Wedge resections were performed for tumors ⬍ 1.5 cm and a ground glassopacity of ⬎ 75% and located ⬍ 2 cm deep from lung surface Surgical margins were greater than tumor diameter Surgical margins were ⬎ 1 cm; includes 29 patients with few comorbidities (“intentional”) and 55 patients with several comorbidities (“conservative”)

Unspecified whether any of the tumors were BAC.

BAC ⫽ bronchoalveolar carcinoma; L ⫽ left; LLD ⫽ left lingular division; LLL ⫽ left lower lobe; LUD ⫽ left upper division; LUL ⫽ left upper lobe; R ⫽ right; RLL ⫽ right lower lobe; RML ⫽ right middle lobe; RUL ⫽ right upper lobe; S ⫽ segment; VATS ⫽ video-assisted thoracoscopic surgery.

NSCLC ⫽ non-small cell lung cancer;

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Results are reported as mean ⫾ standard error or median (range) when data available.

BAC (%)

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Patient No.

Lead Author

a

Gender

Year Published

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Table 2. Operative Variables Year Patient Estimated Blood Chest Tube Number of Nodal Lymph Nodes Published No. Operative Time Loss Duration Stations Dissected Harvested

VATS Segmentectomy Houck Shiraishi Iwasaki Watanabe Atkins Shapiro Schuchert Oizumi Leshnower Sugi Nakamura Gossot Yamashita Moroga Moroga Dylewski Yamashita Thoractomy Segmentectomy Shiraishi Atkins Schuchert Leshnower VATS Lobectomy Iwasaki Shapiro Sugi Nakamura Yamashita VATS Wedge Resection Sugi Nakamura a

With sentinel lymph node biopsy.

2004 2004 2004 2009 2007 2009 2009 2009 2010 2010 2011 2011 2011 2011 2011 2012 2012

11 34 40 41 48 31 104 30 15 43 38 50 90 20a 63b 35 90

... 240 ⫾ 72 ... 220 ⫾ 56 136 ⫾ 45 ... 136 (120–152) 216 (146–425) 145 ⫾ 55 ... ... 188 ⫾ 54 257 ⫾ 91 303 ⫾ 103 241 ⫾ 82 146 (82–229) 257 ⫾ 91

... 169 ⫾ 168 ... 183 ⫾ 195 250 ⫾ 200 ... 171 (133–209) 100 (3–305) ... ... ... 91 ⫾ 82 132 ⫾ 181 182 ⫾ 291 118 ⫾ 127 50 (20–100) 132 ⫾ 181

... 4.5 ⫾ 3.2 ... 3⫾2 3.5 ⫾ 4 2 (1–33) ... 1 (1–7) 2.8 ⫾ 1.3 ... ... 3.3 ⫾ 1 4.8 ⫾ 3.4 4.6 ⫾ 3.4 5.1 ⫾ 3.8 200 (100–400) 4.8 ⫾ 3.4

... ... ... 8⫾2 4.1 ⫾ 3 5 ... ... 3⫾1 0 ... 3.5 ⫾ 1 ... ... ... 5 (3–6) ...

... ... ... 25 ⫾ 10 ... 10 6.4 (5.3–7.5) ... 4⫾3 0 ... 18 ⫾ 8 ... 15.9 ⫾ 10 10.9 ⫾ 8 ... ...

2004 2007 2009 2010

25 29 121 26

204 ⫾ 70 130 ⫾ 65 143 (132–154) 140 ⫾ 38

212 ⫾ 301 280 ⫾ 200 220 (171–269) ...

6.1 ⫾ 4.9 3.7 ⫾ 1 ... 5.2 ⫾ 3.0

... 3.9 ⫾ 3 ... 3⫾2

... ... 9.1 (7.8–10.4) 6⫾5

2004 2009 2010 2011 2012

100 113 95 289 124

... ... ... ... 276 ⫾ 82

... ... ... ... 202 ⫾ 437

... 3 (2–35) ... ... 5.5 ⫾ 4.2

... 5 ... ... ...

2009 2011

21 84

... ...

... ...

... ...

... ...

b

... 10 ... ... 21 ⫾ 9.1 ... ...

Without sentinel lymph node biopsy.

VATS ⫽ video-assisted thoracoscopic surgery.

atrial fibrillation (9.6% versus 5.8%; p ⫽ 0.32) and prolonged air leak (⬎ 5 days) (7.7% versus 6.6%; p ⫽ 0.8). The authors found a trend toward reduced rates of locoregional recurrences in the VATS group (4.8% versus 10.7%; p ⫽ 0.14). Similarly, there was a trend toward reduced overall recurrence rates in the VATS group (16.3% versus 24.0%; p ⫽ 0.10). A margin–tumor size ratio greater than 1 was associated with significantly fewer recurrences (14.7%) than a ratio less than 1 (28.9%; p ⫽ 0 .037). The VATS group had shorter follow-up (16 months) than the open group (28.2 months) because of VATS having been started more recently in the author’s program. However, when adjusted for follow-up, the Kaplan-Meier estimates showed no differences in overall and recurrence-free survival between the 2 groups. The authors additionally performed a propensity analysis that revealed no apparent difference in recurrence-free (p ⫽ 0.996) or overall (p ⫽ 0.605) survival. Interestingly,

the authors did not find a difference in locoregional or overall survival between groups with tumors larger than 2 cm and tumors smaller than 2 cm. In 2010, Leshnower and colleagues [24] compared the results of VATS (n ⫽ 17) versus thoracotomy segmentectomy (n ⫽ 26). This study included patients with primary and metastatic disease. The VATS segmentectomies performed included 9 for primary NSCLC; the open group included 14 for NSCLC. The 2 groups were well matched for age, tumor size, sex, body mass index, comorbidities, and pulmonary function. All patients underwent R0 resection, had an average of 3 lymph node stations sampled, and had similar numbers of lymph nodes sampled (VATS 4.0 ⫾ 3 versus open 6.1 ⫾ 5; p ⫽ 0.40). There was no significant difference between the groups in operative time and no conversions from VATS to thoracotomy. There were no 30-day mortalities in the VATS group, but there were 2 (4.8%) in the thoracotomy

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Table 3. Overall Complication Rates Lead Author VATS Segmentectomy Houck Shiraishi Watanabe Atkins Shapiro Schuchert Oizumi Leshnower Sugi Morogaa Morogab Yamashita Dylewski Thoractomy Segmentectomy Shiraishi Atkins Schuchert Leshnower VATS Lobectomy Shapiro Sugi Yamashita VATS Wedge Resection Sugi

Year Patient Complication Published No. Rate (%) 2004 2004 2009 2007 2009 2009 2009 2010 2010 2011 2011 2012 2011

11 34 41 48 31 104 30 15 43 20 63 90 35

18.0 11.8 9.7 31.3 25.8 26.0 6.9 0.0 11.6 15 22 19.0 11.4

2004 2007 2009 2010

25 29 121 26

20.0 34.5 33.9 34.6

2009 2010 2012

113 95 124

26.6 9.4 23

2009

21

0

a Segmentectomies performed with sentinel lymph node bib Segmentectomies performed without sentinel lymph node opsy. biopsy.

VATS ⫽ video-assisted thoracoscopic surgery.

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group. There was a significant reduction in duration of chest tube use in the VATS group (VATS 2.8 ⫾ 1.3 versus open 5.2 ⫾ 3 days; p ⫽ 0.001) and reduction in hospital length of stay (VATS 3.5 ⫾ 1.4 versus open 8.3 ⫾ 6 days; p ⫽ 0.01). The VATS group had no complications, whereas the open group had 34.6% complications. In addition, the authors examined costs, showing that average hospital costs were approximately $1,700 less for the VATS group.

Advantages of Thoracoscopic Segmentectomy Over Open Segmentectomy? In summary, these 4 studies show that the VATS segmentectomy is feasible and safe [12, 22–24]. These studies preliminarily demonstrate that compared with the open approach, VATS segmentectomy is associated with equivalent oncologic results, with shorter length of stay, reduced rate of morbidity, and lower cost. Specific reductions in complications experienced by the VATS group include fewer infections [23], fewer pulmonary complications [23, 24], fewer cardiac complications [24], and reductions in the duration of chest tube use [12, 24]. Leshnower and colleagues [24] also noted a reduction in

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costs of $1,700, although the finding was not statistically significant. All studies have shown 30-day mortality to be 0% for the VATS group compared with a range from 1.7% to 7.7% 30-day mortality for open segmentectomy. All 4 studies demonstrated fewer overall complications with the VATS approach compared with the thoracotomy approach. The importance of surgeon experience is highlighted in the findings of these studies. One study showed longer operative time [22], whereas the other 3 studies showed similar operative times [12, 23, 24]. Leshnower and colleagues [24] found no difference in lymph nodes harvested between the 2 groups, whereas Schuchert and colleagues [23] reported fewer lymph nodes harvested with the VATS approach. Future studies would add to the literature by factoring surgeon experience into the analysis. Long-term survival analysis and randomized studies that eliminate surgeon bias are also necessary to determine whether there is an advantage of the VATS segmentectomy over the open approach.

Thoracoscopic Segmentectomy Versus Lobectomy Versus Wedge Resection The role and outcomes of thoracoscopic segmentectomy as opposed to thoracoscopic lobectomy or thoracoscopic wedge resection are also under current investigation. Harada and colleagues [25] performed an analysis of pulmonary function for patients undergoing VATS segmentectomy (n ⫽ 38) or VATS lobectomy (n ⫽ 45) for NSCLC. The tests were performed preoperatively and at 2 and 6 months postoperatively. The tests included forced vital capacity, FEV1, and anaerobic threshold. Both groups had similar preoperative function. The segmentectomy group had approximately 50% fewer segments resected than did the lobectomy group. The authors found that the number of resected segments was significantly associated with decreased forced vital capacity and decreased FEV1 at 2 and 6 months after operation (p ⬍ 0.0001). The segmentectomy patients regained exercise capacity 6 months postoperatively in contrast to the lobectomy patients, who experienced a 10% loss in exercise capacity. In 2004, Iwasaki and colleagues [26] compared the outcomes of 100 patients who underwent VATS lobectomy with those of 40 patients who underwent VATS segmentectomy for pathologic stage I and stage II NSCLC. There were 81 men and 59 women; mean age of the patients was 66 years. Seventy-eight percent of the patients had adenocarcinoma and 22% had squamous cell carcinoma. In addition, the authors had performed dissection of hilar and mediastinal lymph nodes that were in pathologic stage I or II, although no details about the lymph nodes dissected were included in the study. The VATS segmentectomy group had a similar 5-year survival rate compared with the VATS lobectomy group (77.8% versus 76.7%; p ⫽ 0.47). In 2009, Shapiro and colleagues [27] performed a retrospective review of 31 consecutive patients who underwent thoracoscopic segmentectomy versus 113 consecu-

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Table 4. Overall Hospital Length of Stay Lead Author

Year Published

Patients No.

Mean Length of Stay (days)

Median Length (range) of Stay (days)

2004 2007 2004 2009 2009 2010 2011 2011 2011 2012

11 48 34 31 104 15 20 63 35 90

4.3 ⫾ 3.1 4.3 ⫾ 3 12.7 ⫾ 3.6 ... 6.4 (5.5–7.3)a 3.5 ⫾ 1.4 10.4 ⫾ 3.5 12.8 ⫾ 9.1 ... 12.2 ⫾ 8.2

3 ... ... 4 (1–98) 5 ... ... ... 2 (1–15) ...

2004 2007 2009 2010

25 29 121 26

16.7 ⫾ 7.7 6.8 ⫾ 6 8.2 (7.3–9.1)a 8.3 ⫾ 6.1

... ... 7 ...

2009 2012

113 124

... 11.6 ⫾ 5.4

4 (3–34) ...

VATS Segmentectomy Houck Atkins Shiraishi Shapiro Schuchert Leshnower Morogab Morogac Dylewski Yamashita Thoracotomy Segmentectomy Shiraishi Atkins Schuchert Leshnower VATS Lobectomy Shapiro Yamashita a

Results are reported as mean and 95% confidence interval. performed without sentinel lymph node biopsy.

b

Segmentectomies performed with sentinel lymph node biopsy.

c

Segmentectomies

tive patients who underwent thoracoscopic lobectomy for early-stage NSCLC. The groups were well matched in age and staging, with mean follow-up of approximately 22 months. However, the segmentectomy group had longer exposure to smoking (47.8 versus 34.4 pack years) and significantly worse preoperative pulmonary function than the lobectomy group (FEV1 83% versus 92%; p ⫽ 0.04). Despite the difference in health, postoperative recovery, and follow-up, results were similar between the groups. There were no differences in complication rates between the 2 groups. There were no perioperative deaths in the segmentectomy group but there was 1 death in the lobectomy group. Median length of stay was 4 days in each group. There was a 3.5% local recurrence rate in the segmentectomy group and a 3.6% local recurrence rate in the lobectomy group. The total recurrence rate was 17% in the segmentectomy group and 20% in the lobectomy group. The mean follow-up for the segmentectomy and lobectomy groups were 21 and 22 months, respectively. There were no statistical differences between the groups in overall and disease-free survival rates (p ⬎ 0.5). In 2010, Sugi and colleagues [28] conducted a retrospective review of 159 patients who underwent thoracoscopic surgery for NSCLC. Twenty-one patients underwent VATS wedges, 43 underwent VATS segmentectomies, and 95 underwent VATS lobectomy. Patients in the VATS wedge group had tumors that were smaller than 1.5 cm and less than 2 cm deep from the lung surface, with ground glass-opacity of greater than 75%. No hilar or mediastinal lymph nodes were assessed. Patients in the segmentec-

tomy group who did not fulfill the criteria for wedge resection and had tumors smaller than 2 cm that were located deeper in the lobe. They additionally underwent hilar lymph node dissection with lobe-specific mediastinal node sampling. Patients in the lobectomy group had tumors smaller than 3 cm that did not fulfill the author’s criteria for wedge resection or segmentectomy. In addition, these patients underwent hilar and mediastinal lymph node dissection. The complication rate was 0% in the wedge resection group, 11.6% in the segmentectomy group, and 9.4% in the lobectomy group. The percentage of patients with pathologic stage higher than pT1N0 was greater in the lobectomy group than in the segmentectomy group (18% versus 8%; p ⫽ 0.07). There were no data on the pathologic stage for the wedge resection group, but the tumor size in this group (tumor ⬍ 1.5 cm) was smaller than the other 2 groups. Patients were followed for 5 years. There were no significant differences among the groups in 5-year recurrence-free and overall survival. In 2010, Leshnower and colleagues [24] compared the results of VATS (n ⫽ 15) versus thoracotomy segmentectomy (n ⫽ 26). This study included patients with primary and metastatic disease. For primary NSCLC, there were 9 VATS segmentectomies and 14 open segmentectomies performed. The 2 groups were well matched for age, tumor size, sex, body mass index, comorbidities, and pulmonary function. All patients underwent R0 resection, had an average of 3 lymph node stations sampled, and had similar numbers of lymph nodes sampled (VATS 4.0 ⫾ 3 versus open 6.1 ⫾ 5; p ⫽ 0.40). There was

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Table 5. Overall Survival Rates

Lead Author

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VATS Segmentectomy Houck Iwasaki Shiraishi (intentional) Shiraishi (compromised) Watanabe Atkins Shapiro Oizumi Schuchert Leshnower Sugi Morogaa Morogab Nakamura Yamashita Dylewski Yamashita Thoracotomy Segmentectomy Atkins Schuchert Leshnower VATS Lobectomy Iwasaki Shapiro Sugi Nakamura Yamashita Yamashita VATS Wedge Resections Sugi Nakamurad Nakamurae

Year Published

Patient No.

Mean Follow-up (months)

30–day Mortality (%)

1-Year

2-Year

3-Year

4-Year

5-Year

2004 2004 2004 2004 2009 2007 2009 2009 2009 2010 2010 2011 2011 2011 2011 2011 2012

11 40 22 12 41 48 31 30 104 15 43 20 63 38 38 35 90

13.5 ... 21.9 26.1 70 ... 22 ... 16.2 ... 60 18.1 18.1 29.3 27.5c ... 30c

0 ... 0 0 0 0 0 0 0 0 ... ... ... ... 0 0 0

100 ... ... ... ... ... 100 ... ... ... ... 80 90 ... ... ... ...

... ... ... ... ... 87 ... ... ... ... ... ... ... ... ... ... ...

... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ...

... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ...

... 76.7 100 47.7 89.3 ... ... ... ... ... 87.9 ... ... 87.2 87 ... 75

2007 2009 2010

29 121 26

... 28.2 ...

6.9 1.7 7.7

... ... ...

54 ... ...

... ... ...

... ... ...

... ... ...

2004 2009 2010 2011 2011 2012

100 113 95 289 71 124

... 21 60 41.8 27.5 30c

... 1 ... ... 0

... 96.7 ...

... ... ...

... ... ...

... ... ...

...

...

...

...

77.8 ... 87.3 82.1 84 84

2009 2011 2011

21 29 55

60 37 37

... ... ...

... ... ...

... ... ...

... ... ...

... ... ...

a

Overall Survival (%)

b Segmentectomies performed with sentinel lymph node biopsy. Segmentectomies performed without sentinel lymph node biopsy. d e Conservative group ⫽ patients with multiple comorbidities. Median, not mean. tional group ⫽ patients with few comorbidities.

95.2 83.3 49.1 c

Inten-

VATS ⫽ video-assisted thoracoscopic surgery.

no significant difference between the groups in operative time and no conversions from VATS to thoracotomy. Thirty-day mortality was 0% in the VATS group and 4.8% in the thoracotomy group. There was a significant reduction in duration of chest tube use in the VATS group (VATS 2.8 ⫾ 1.3 versus open 5.2 ⫾ 3 days; p ⫽ 0.001) and reduction in hospital length of stay (VATS 3.5 ⫾ 1.4 versus open 8.3 ⫾ 6 days; p ⫽ 0.01). The VATS group had no complications, whereas the open group had a 34.6% rate of complications. In addition, the authors examined costs, showing that average hospital costs were approximately $1,700 less for the VATS group. In 2011, Yamashita and colleagues [29] performed a retrospective review comparing the outcomes of 38 patients who underwent thoracoscopic segmentectomy

with 71 patients who underwent thoracoscopic lobectomy with systemic lymphadenectomy. The local recurrence rate in the segmentectomy group (7.9%) was slightly higher than that in the lobectomy group (5.6%), but the difference was not statistically significant. In addition, there were no differences in recurrence-free and overall survival between the 2 groups. Higher stage was found to be associated with decreased survival, whereas the type of operation was not. A limitation to this study was that there were differences in the tumor size between the 2 groups (median size was 1.5 cm for the segmentectomy group versus 2.5 cm for the lobectomy group; p ⬍ 0.0001). In 2011, Nakamura and colleagues [30] compared the results of VATS lobectomy (n ⫽ 289) to that of VATS

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Table 6. Overall Recurrence-Free Survival Rates

Lead Author VATS Segmentectomy Houck Iwasaki Watanabe Shapiro Sugi Morogaa Morogab Yamashita VATS Lobectomy Iwasaki Shapiro Sugi Yamashita VATS Wedge Resections Sugi a

Overall Recurrence–Free Survival

Year Published

Patient No.

Mean Follow-up (months, range)

1-Year

2-Year

3-Year

4-Year

5-Year

2004 2004 2009 2009 2010 2011 2011 2012

11 40 41 31 43 20 63 90

13.5 (3–32) ... 70 22 60 18.1 18.1 30

100% ... ... 94.4 ... ... ... ...

... ... ... ... ... 100 84 ...

... ... ... ... ... ... ... ...

... ... ... ... ... ... ... ...

... ... 93.3 ... 93.8 ... ... 81

2004 2009 2010 2012

100 113 95 124

... 21 60 30

... 93.3 ... ...

... ... ... ...

... ... ... ...

... ... ... ...

... ... 93.4 89

2009

21

60

...

...

...

...

Segmentectomies performed with sentinel lymph node biopsy.

b

100

Segmentectomies performed without sentinel lymph node biopsy.

segmentectomy (n ⫽ 38) and VATS wedge resection (n ⫽ 84) for patients with NSCLC [30]. With regard to procedure selection, the default operation was a lobectomy, although patients would undergo sublobar resection if they had impaired cardiopulmonary, renal, or liver function, unstable malignancy of other organs, and psychiatric disease. Segmentectomy was selected for the patient if the tumor was deep within the lung parenchyma or the diameter of the tumor was greater than 2 cm, or both. Otherwise a wedge resection with surgical margins greater than 1 cm was performed. Wedge resections were further classified as “intentional” (low-risk) or “conservative” when multiple comorbidities were present. The lobectomy group had mean tumor sizes (2.57 cm) that were significantly larger than the segmentectomy (19.8 cm) and wedge resection groups (18.5 cm). The 5-year survival rates for lobectomy, segmentectomy, and wedge resection were 90.0%, 100.0%, and 71.2%, respectively. Within the wedge resection group, the intentional lowrisk group (n ⫽ 29) had an 83.3% 5-year survival versus the conservative high-risk group (n ⫽ 55) with a 41.1% 5-year survival (p ⫽ 0.007). The recurrence rates for lobectomy, segmentectomy, and wedge resection were 18.0%, 7.9%, and 15.5%, respectively. The authors concluded that outcomes for VATS wedge resections were inferior to those of lobectomy and segmentectomy. However, the wedge resection group had a large percentage of patients with multiple comorbidities who were sicker than patients in the other groups. The intentional lowrisk group within the wedge resection category had survival rates similar to those of the segmentectomy and lobectomy groups. In 2012, Yamashita and colleagues [31] performed a retrospective review of 90 patients who underwent tho-

racoscopic segmentectomy versus 124 patients who underwent thoracoscopic lobectomy for stage IA NSCLC. The groups were well matched for age, sex, and histologic type, and had median follow-up of approximately 30 months. The segmentectomy group had a greater percentage of patients with T1a tumors compared with the lobectomy group (84% versus 58%; p ⬍ 0.001). Median tumor size was 15 mm for the segmentectomy group versus 20 mm for the lobectomy group. There were no significant differences in blood loss, duration of chest tube use, operating time, and hospital stay between the 2 groups. The segmentectomy group had significantly fewer mean numbers of dissected lymph nodes compared with the lobectomy group (12.1 versus 21; p ⬍ 0.0001). The authors noted that this could be related to the number of inter- or intrasegmental nodes or to the possibility that when tumors were in the S1–S3 segments, upper mediastinal node dissections without subcarinal node dissections were performed. There were no significant differences in morbidity, 30-day mortality, recurrence, or disease-free and overall survival for both groups.

Advantage of Thoracoscopic Segmentectomy Over Thoracoscopic Lobectomy? These studies demonstrate that thoracoscopic segmentectomy may have some advantages over thoracoscopic lobectomy in selected patients. Although thoracoscopic segmentectomy is a more complex procedure than thoracoscopic lobectomy [15], the rates of morbidity, recurrence, and survival seem to be equivalent. Specifically, the 2 groups have been found to have similar overall complication rates [27, 28, 31], lengths of hospital stay [27,

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31], local recurrence rates [27, 28, 31], 5-year recurrencefree survival [28, 29, 31], and 5-year survival rates [26, 28, 29, 31]. Preliminarily, thoracoscopic segmentectomy was also shown to preserve greater lung function and exercise capacity than does thoracoscopic lobectomy, although these data are based on follow-up of 6 months, and long-term data are needed [25]. There are limitations to the preceding studies. First, the lobectomy group had larger tumors than did the segmentectomy group, a difference that was statistically significant [25–29, 31]. However, other studies have demonstrated that in appropriately selected small tumors, thoracoscopic segmentectomy may be advantageous. In 2006, Okada and colleagues [32] conducted a study of 567 patients in 3 institutions and limited the analysis to patients with tumor size less than 2 cm. Mean tumor sizes for the segmentectomy and lobectomy groups were 1.57 cm and 1.62 cm (p ⫽ 0.0564), respectively. The authors found that segmentectomy was associated with equivalent 5-year survival compared with lobectomy for lesions less than 2 cm in diameter (83.4% versus 85.9%, respectively). Second, the fraction of patients with bronchoalveolar carcinoma or adenocarcinoma in situ was not reported in these referenced studies, with the exception of 1 study [31]. It is important to control for this variable, as demonstrated by a study performed by Nakayama and colleagues [33] that examined the results of 63 patients with adenocarcinoma who underwent open sublobar resection of clinical stage IA (T ⬍ 2 cm) NSCLC [33]. The authors limited the analysis to patients with adenocarcinoma who underwent sublobar resection (either segmentectomy or wedge resection). In addition, they further classified the tumors as either “air-containing type” (n ⫽ 46) or “solid-density type” (n ⫽ 17) according to the tumor shadow disappearance rate on high-resolution CT. After resection, 38 of the 46 air-containing tumors were identified as bronchoalveolar carcinomas. Air-containing tumors had a significantly better overall 5-year survival than solid-density tumors (95% versus 69%; p ⬍ 0.0001). With regard to VATS wedge resections, there are currently only 2 studies that compare the procedure with VATS segmentectomy and lobectomy. In those studies, in the wedge resection group the tumors were smaller [28, 30] or the patient population was sicker [30]. It is difficult to infer from those 2 studies whether VATS wedge resections are appropriate procedures; more studies will be needed in this area. Further research is also required regarding selection criteria for thoracoscopic segmentectomy. Based on current data, it seems reasonable to consider segmentectomy for patients with air-containing tumors (groundglass opacities) less than 2 cm in diameter when an acceptable segmental margin is obtainable (margin greater than or equal to tumor diameter), particularly in patients with advanced age, poor performance status, or poor cardiopulmonary reserve [34]. Future studies would benefit from controlling for tumor size, type of cancer, tumor location, and resection margin. Two ongoing studies will improve our understanding of the outcomes of limited resection for NSCLC [35, 36].

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The first study, sponsored by the Alliance for Clinical Trials in Oncology (CALGB 140503) [35], will evaluate the outcomes of patients who are randomly assigned to undergo limited resection (segmentectomy or wedge resection) or lobectomy, with the VATS or thoracotomy approach determined by the surgeon. The second study is sponsored by the Japan Clinical Oncology Group and the West Japan Oncology Group (JCOG0802/ WJOG4607L) [36]. This study will evaluate outcomes in patients who are randomly assigned to undergo segmentectomy or lobectomy; it does not include wedge resections as a possible procedure. Both studies will clarify the role of segmentectomy. However, CALGB 140503 may be limited in its final analysis by including patients who undergo wedge resection (as opposed to segmentectomy) in the limited-resection group. In addition, in both CALGB 140503 and JCOG0802/WJOG4607L, the operative approach—VATS versus open operations—is not a primary outcome variable.

Technical Considerations Although the thoracoscopic approach may be used for any anatomic segmental resection, the most commonly performed segmental resections are lingula-sparing left upper lobectomy, lingulectomy, superior segmentectomy, and basilar segmentectomy. Contraindications to thoracoscopic segmentectomy include the inability to achieve complete resection with segmentectomy; in patients with lung cancer, the parenchymal margin should be at least the diameter of the tumor [15, 37]. The operative strategy for thoracoscopic segmentectomy is similar to that of thoracoscopic lobectomy. In general, segmentectomy is performed with division of segmental vessels and bronchi in a manner similar to the open approach. The approach to thoracoscopic segmentectomy begins with ligation of the segmental pulmonary vein, followed by either the bronchus or artery, depending on the segment. The parenchymal excision is accomplished by stapling in intersegmental fissures. Bi- or trisegmentectomy is performed when tumors are close to intersegmental fissures. All specimens are removed in a protective bag. Although the feasibility of thoracoscopic segmentectomy has been demonstrated [15, 37], there is still controversy regarding technical issues, such as the demonstration of the segmental plane and the technique of parenchymal division. The standard technique involves temporary reinflation of the ipsilateral lung after bronchial ligation to demarcate the plane [15]. In 2007, Okada and colleagues [38] reported a novel method to detect the intersegmental plane in VATS segmentectomy that involved selective jet ventilation during bronchoscopy. They identified the intersegmental plane by differential inflation of the involved segment with jet ventilation. After demarcation of the segmental plane, completion of the parenchymal division may be completed in several ways, using a linear stapler or energy devices [15]. Okada and colleagues recommend dissection of the segmental

plane by electrocautery to preserve segmental anatomy and pulmonary function [32]. Lung inflation techniques have drawbacks, particularly in cases of severe emphysema, in which lungs can be easily overinflated and surgical views can become limited [39]. In 2010, Misaki and colleagues [39] developed a method for visualizing adjacent lung segments without lung inflation that was tested on 8 patients. The authors ligated the dominant pulmonary artery of the target segment, injected indocyanine green into a peripheral vein, and observed lung segments using an infrared thoracoscopy system. In 2012, Sekine and colleagues [40] tested a different method for determining intersegmental lines in 10 patients. The authors injected indocyanine green into the target segmental or subsegmental bronchus. This was followed by introduction of 200 to 300 cc of air into the bronchus to distribute the indocyanine green into the periphery. The indocyanine green and intersegmental line were detected by infrared thoracoscopy. The authors compared results with a control group and found no differences in operative time, postoperative chest drainage, or postoperative complications. Interestingly, length of stay was shorter in the intervention group than in the control group (p ⫽ 0.055). The use of advanced radiologic techniques to improve the technical completion of segmentectomy has been demonstrated [41, 42]. Yamada and colleagues [41] applied multidetector row computed tomographic angiography to assess the relationship of the pulmonary tree to the tumor, to assist with isolation of the pulmonary vessels, and to determine the resection line. The authors noted that when confronted with deep pulmonary lesions, multidetector row computed tomographic angiography may be considered in preoperative planning of thoracoscopic segmentectomy. Localization of small tumors in a specific segment may be particularly challenging when the tumor is less than 1 cm in diameter and not in an immediate subpleural location. Tumor localization techniques include using local injection of radiotracer [43], wire hook and coil markers [44], radiopaque markers using intraoperative fluoroscopy [45, 46], and navigational bronchoscopy [47]. However, other investigators have demonstrated that successful localization may be achieved in the majority of patients without these techniques [15]. The role of energy sources in vessel ligation has been investigated in animal models and in human series [48, 49]. A technical challenge in VATS segmentectomy has been dissection of pulmonary arteries, particularly the right upper lobe posterior ascending pulmonary artery—a task made more difficult with current bulky stapling devices. Nicastri and colleagues [48], in a porcine model, showed that a small ultrasonic scalpel was successful in achieving vessel ligation in 76% of pulmonary arteries and 92% of veins, with no failure in arteries 5 mm or less and veins 7 mm or less. There have also been reports exploring the application of the LigaSure bipolar tissue fusion system (Covidien, Mansfield, MA) for division of pulmonary arterial and venous branches during anatomic lung resection, the largest of which was per-

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formed by Schuchert and colleagues [49]. The authors applied the energy-based coagulative fusion technology in 211 patients during 104 lobectomies and 107 anatomic segmentectomies. They found the LigaSure Atlas (Covidien), which applied a seal 6 mm wide ⫻ 22 mm in length, resulted in no arterial or venous dehiscences (vessel size range, 0.4 –1.2 cm) during division of 476 pulmonary arteries and 229 veins. They concluded the technology could be used safely and effectively for the division of both pulmonary arteries and veins, particularly vessels less than 7 mm in diameter. These studies have been promising, but further data with long-term follow-up and larger sample sizes will be needed to more definitively address applicability of the technology in the human pulmonary vasculature. To eliminate unnecessary lymph node dissection in patients with lung cancer, some groups are using indocyanine green fluorescence image-guided surgical procedures for sentinel lymph node biopsy [50, 51]. In 2011, Moroga and colleagues [50] performed a retrospective study of 63 patients who underwent VATS segmentectomy versus 20 patients who underwent VATS segmentectomy with sentinel lymph node biopsy using indocyanine green fluorescence imaging. In the sentinel lymph node group, the authors identified sentinel lymph nodes in 16 of 20 patients, with a false-negative rate of 0%. Median follow-up was 18.1 months. There were no differences in morbidity, mortality, and overall and recurrence-free survival between the 2 groups.

Feasibility of Mediastinal Lymph Node Dissection Mediastinal lymph node assessment is an important component of thoracoscopic segmentectomy for NSCLC, although the advantage of complete mediastinal lymph node assessment as opposed to systematic sampling is uncertain [52]. Thoracoscopic segmentectomy has been shown to achieve adequate lymph node dissection [24, 27]. Leshnower and colleagues [24] demonstrated no differences in lymph nodes sampled between VATS and open segmentectomy. Shapiro and colleagues [27] noted that thoracoscopic segmentectomy was equivalent to lobectomy in terms of lymph nodes dissected, with both groups undergoing dissection of 5 nodal stations, resulting in an average of 10 lymph nodes available for pathologic evaluation and staging.

Limitations and Future Study Because of the retrospective nature of these studies, there was the potential for surgeon bias to affect the type of operation a patient received. For example, in some studies patients in the VATS segmentectomy group were sicker than those in the comparison group [23, 27–29]. This may have underestimated the benefit of VATS segmentectomy. In other studies, the VATS group had slightly smaller tumors than did those in the comparison group [23, 26, 28, 29, 31]. In this case, the studies may have overestimated the benefits of VATS segmentectomy.

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The current studies reviewed did not report tolerance of patients for resection of secondary cancers. This would be an important feature to measure, given that as many as 11.5% of patients who undergo resection of lung cancer have additional primary lung cancers develop within their lifetimes [27, 53]. VATS segmentectomy, by inducing less trauma than does open segmentectomy and additionally preserving more lung function than does lobectomy, would be hypothesized to offer patients higher tolerance for resection of secondary cancers than those patients undergoing lobectomy or open segmentectomy. In addition, future studies should aim to improve on the current lack of documentation on number of nodes sampled or dissected. All but 2 of the studies in this review [24, 27] described the degree of lymph node sampling. Finally, as already discussed, the role of VATS segmentectomy may be clarified by the 2 ongoing randomized controlled trials CALGB 140503 and JCOG0802/ WJOG4607L [35, 36]. The outcomes of these 2 studies and additional well-designed studies on VATS segmentectomy will become increasingly important in light of national and international lung cancer screening trials. Although the thoracoscopic strategy may be difficult to learn, it is increasingly becoming the preferred method of anatomic pulmonary resection. In light of the outcome of the National Lung Screening Trial [54], the use of thoracoscopic procedures is certain to increase [55]. In the future, minimally invasive strategies will be more commonly used in the management of selected patients with small tumors (⬍ 2 cm), in patients with previous pulmonary resections, and in patients with limited cardiopulmonary reserve.

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