Feasibility and oncological outcomes of laparoscopic rectal resection following neo-adjuvant chemo-radiotherapy: A systematic review

Table 1 Search strategy

Search strategy
1 Rectal adenocarcinoma - tracked to MeSH to include all subheadings and combining with OR and clicking the Explode box; limit to English language and Humans - no time limits selected
2 Surgery - tracked to MeSH to include all subheadings and combining with OR and clicking the Explode box; limit to English language and Humans - no time limits selected
3 Laparoscopy - tracked to MeSH to include all subheadings and combining with OR and clicking Explode box; limit to English language and Humans - no time limits selected
4 Minimally invasive surgery - tracked to MeSH to include all subheadings and combining with OR and clicking Explode box; limit to English language and Humans - no time limits selected
5 Anterior Resection - Keyword search only (not linked to MeSH headings)
6 Neo-adjuvant chemo-radiotherapy
7 Proctectomy - Keyword search only (not linked to MeSH headings)
8 Total Mesorectal Excision - Keyword search only (not linked to MESH headings)
9 Combine 1 and 2 and 5 and 6 and 7 and 8
10 Combine 1 and 3 and 4 and 5 and 6 and 7 and 8

Table 2 Overview of studies with extractable data

Ref.	Year	Country	Type of study	Total No. of patients	Patients Lap	Patients open
Kang et al[9]	2010	South Korea	RCT	340	170	170
Kusano et al[11]	2014	Japan	Case control Study	33	19	14
Hu et al[14]	2013	China	Case control Study	137	51	86
Seshadri et al[12]	2011	India	Case control Study	144	72	72
Denoya et al[15]	2009	United States	Case matched series	64	32	32
1Saklani et al[13]	2013	South Korea	Case series	64	64	NA
1Denost et al[10]	2011	France	Case series	292	292	NA
Motson et al[7]	2011	United Kingdom	Case series	26	26	NA

¹Data pertaining to LCRT + laparoscopic resection group of the study only extracted therefore treated as case series. NA: Not applicable; LCRT: Long course chemo-radiotherapy; RCT: Randomized controlled trial.

Table 3 Studies from which data could not be extracted (sub group analysis not described/reported)

Ref.	Year	Country	Type of study	Percent having LCRT in Lap group
van der Pas et al[5]	2013	The Netherlands	RCT1	59
Lujan et al[6]	2009	Spain	RCT	72.3
Lujan et al[16]	2013	Spain	Case Control	58.1
McKay et al[17]	2012	Australia	Case Control	48.8
Laurent et al[18]	2011	France	Case Control	93.6
Patel et al[19]	2011	United States	Case Matched	50
Li et al[20]	2011	China	Case Control	34.5
Kellokumpu et al[21]	2011	Finland	Case Control	34
Greenblatt et al[22]	2011	United States	Case Control	31.6
da Luz Moreira et al[23]	2011	United States	Case Matched	33
Baik et al[24]	2010	United States	Case Matched	79.6
Westerholm et al[25]	2012	Canada	Case Series	7.4
Jefferies et al[26]	2011	United Kingdom	Case Series	43.8
Glancy et al[27]	2011	United Kingdom	Case Series	8
Lam et al[28]	2010	Belgium	Case Series	56.7
Sartori et al[29]	2010	Italy	Case Series	39.1
Cheung et al[30]	2010	Hong Kong	Case Series	21.5
Park et al[31]	2010	South Korea	Case Series	8.1

¹Patients in this trial had short course radio therapy. LCRT: Long course chemo-radiotherapy; RCT: Randomized controlled trial.

Table 4 Comparison of criteria for long course chemo-radiotherapy and regimes

Ref.	Staging imaging	Criteria for LCRT	Chemo agent	Rad dose/duration
Kang et al[9]	CT, MRI, ERUS	cT3N0-2 M0 Mid/low rectal cancer	I/V 5FU + leucovorin or oral capecitabine	50.4 Gy over 5.5 wk (tumour boost used)
Kusano et al[11]	CT, MRI	T3N0-3M02	Different protocols	Total dose = 45 Gy/duration not reported
Hu et al[14]	CT, MRI, ERUS	Stage 2/3 tumours	Capecitabine and oxaliplatin	50 Gy over 5 wk
1Seshadri et al[12]	CT	T2/T3 N+, T4 excluded	Mitomycin and 5FU	Total dose = 50 Gy/duration not reported
Denoya et al[15]	CT, MRI, ERUS	T3/4 or N+ disease	5FU or Xeloda	Total dose = 50.4 Gy/duration not reported
Saklani et al[13]	NR	T3/4 or N+ disease	5FU	Total dose = 50.4 Gy/duration not reported
Denost et al[10]	CT, MRI, ERUS	T3/4 = 265 (90.8%), T1/2 = 27 (9.2%)	I/V 5FU and leucovorin	45 Gy over 5 wk
Motson et al[7]	CT, MRI	T3/4 N+ + involved/ threatened CRM	5FU or Uftoral	45/50 Gy over 5 wk (3/4 fields)

¹7/72 (Lap) and 6/72 (open) received only RT; cannot separate data;

²Using TNM classification of malignant tumours 7^th edition 2009. NR: Not reported; LCRT: Long course chemo-radiotherapy; CT: Computed tomography; MRI: Magnetic resonance imaging; CRM: Circumferential/radial resection margin; ERUS: Endoluminal rectal ultra-sound.

Table 5 Patient characteristics

Ref.	Age (yr)		Laparoscopic Group		Open Group		BMI		Distance from Anal Verge (cm)		Laparoscopic Group		Open Group
	Lap	Open	Men	Women	Men	Women	Lap	Open	Lap	Open	AR	APR	AR	APR
1Kang et al[9]	57.8 (11.1)	59.1 (9.9)	64.7%	35.3%	64.7%	35.3%	24.1 (3.2)	24.1 (3.2)	5.6 (2.3)	5.3 (2.5)	151 (88.8%)	19 (11.2%)	146 (85.9%)	24 (14.1%)
Kusano et al[11]	58 (32-82)	55 (39-73)	15 (78.9%)	4 (21.1%)	8 (57.1%)	6 (42.9%)	≤ 25 = 14 (73.7%) > 25 = 5 (26.3%)	≤ 25 = 9 (64.3%) >25 = 5 (35.7%)	2 (0-50)	3.7 (0-10)	11 (57.9%)	8 (42.1%)	4 (28.6%)	10 (71.4%)
Hu et al[14]	55 (35-78)	55 (29-82)	34 (66.7%)	17 (33.3%)	56 (65.1%)	30 (34.9%)	23.4 (16-31.2)	24.2 (16.3-36.2)	≤ 5 = 33 (64.7%) > 5 = 18 (35.3%)	≤ 5 = 54 (62.8%) > 5 = 32 (37.2%)	32 (62.7%)	18 (35.3%)	36 (41.9%)	44 (51.2%)
Seshadri et al[12]	48 (22-73)	48 (19-71)	47 (65%)	25 (35%)	45 (62%)	27 (38%)	21 (15-33)	22 (14-38)	3 (0-8)	3 (0-10)	8 (11%)	64 (89%)	8 (11%)	64 (89%)
1Denoya et al[15]	56.3	57.1	19 (59.4%)	13 (40.6%)	18 (56.3%)	14 (43.7%)	25	26.4	4.1	4.6	24 (75%)	8 (25%)	24 (75%)	8 (25%)
Denost et al[10]	65 (20-85)	NA	179 (61.3%)	113 (38.7%)	NA	NA	25 (16-39)	NA	< 5 = 175 (59.9%) > 5 = 117 (40.1%)	NA	NR	NR	NA	NA
Motson et al[7]	63 (39-81)	NA	21 (80.8%)	5 (19.2%)	NA	NA	NR	NA	< 5 = 11 (42.3%) > 5 = 15 (57.7%)	NA	16 (61.5%)	10 (38.5%)	NA	NA

Values reported as median (range) except

¹where it is Mean. NA: Not applicable; AR: Anterior resection; APR: Abdomino-perineal resection; BMI: Body mass index; NR: Not reported.

Table 6 Peri-operative outcomes

Ref.	Interval to surgery	Conversion	Estimated blood loss		Intra-op injury		Diversion stoma
			Lap	Open	Lap	Open	Lap	Open
1Kang et al[9]	26-8 wk	1.2%	Median - 200 mL	Median - 217.5 mL	Yes1	Yes1	91.4%	88.4%
Kusano et al[11]	NR	NR	< 200 mL = 47.4% > 200 = 52.6%	< 200 = 92.9% > 200 = 7.1%	NR	NR	NR	NR
Hu et al[14]	Mean 53 d (28-105 d)	5.9%	Mean 204.7 (80-1000 mL)	Mean 352.5 (100-1200) mL	No	Ureteric injury = 1.2%	NR	NR
Seshadri et al[12]	Median 8 (4-36) wk	4.1%	Median 200 (100-600) mL	Med 400 (150-1500) mL	NR	NR	NR	NR
Denoya et al[15]	Mean 6.5 wk	28.1%	Mean 313 ± 443	Mean 279 ± 229	NR	NR	75%	75%
Denost et al[10]	26 wk	18.8%	NR	NA	NR	NA	81.2%	NA
Motson et al[7]	Median 11 wk	11.5%	NR	NA	NR	NA	75%	NA

¹There were 3 patients in each group needing re-operation - indication for these were not described. Also, one patient in each group had a brachial plexus injury;

²Study protocol - actual durations not mentioned. NR: Not reported; NA: Not applicable.

Table 7 Post-operative complications

Ref.	Anastomotic leak (%)		Pelvic abscess (%)		Post-op Ileus (%)		Acute voiding difficulty (%)		Stoma complications (%)
	Lap	Open	Lap	Open	Lap	Open	Lap	Open	Lap	Open
Kang et al[9]	1.2	0	0	0.6	10	12.9	10	4.1	0.6	0
Kusano et al[11]	0	7.1	10.5	14.2	5.2	7.1	0	7.1	NR	NR
2Hu et al[14]	3.1	8.3	0	1.2	0	1.2	1.2	2.3	0	2
Seshadri et al[12]	4.1	8.3	NR	NR	NR	NR	11	7	NR	NR
Denoya et al[15]	NR	NR	NR	NR	5	5	NR	NR	NR	NR
Denost et al[10]	12.7	NA	NR	NA	NR	NA	NR	NA	NR	NA
1Motson et al[7]	18.7	NA	NR	NA	NR	NA	15.4	NA	NR	NA

¹2 patients had adhesiolysis;

²Other complications, Urinary fistula = 1 and Rectovaginal fistula = 1 both in open group. NR: Not reported; NA: Not applicable.

Table 8 Short term and long term outcomes

Ref.	Post-op length of stay		30 d mortality (%)	Length of follow-up	Local recurrence
	Lap	Open			Lap	Open
Kang et al[9]	8 (7-12)	9 (8-12)	NR	3 mo	NA	NA
Kusano et al[11]	24 (14-92)	35 (14-70)	NR	Median 39 mo	1 (5.2%)	3 (21.4%)
Hu et al[14]	10 (6-34)	16 (6-44)	NR	Short term outcomes only	NA	NA
Seshadri et al[12]	12 (6-45)	15 (10-50)	None	Short term outcomes only	NA	NA
1Denoya et al[15]	6.1 ± 2.4	7.6 ± 2.3	NR	Short term outcomes only	NA	NA
Denost et al[10]	NR	NA	0.3	NR	NR	NA
Motson et al[7]	8 (5-17)	NA	3.8	Median 34 mo	2 (7.6%)	NA
Saklani et al[13]	NR	NA	NR	Median 36 mo	4 (6.3%)	NA

Reported as median (range) except

¹where it is mean. NR: Not reported; NA: Not applicable.

Table 9 Quality markers

Ref.	CRM positivity		Lymph node harvest1
	Lap	Open	Lap	Open
Kang et al[9]	2.9%	4.1%	17 (12-22)	18 (13-24)
3Kusano et al[11]	NR	NR	< 12 = 73.7% > 12 = 26.3%	< 12 = 64.3% > 12 = 35.7%
Hu et al[14]	1.9%	3.5%	12 (2-20)	11 (1-25)
4Seshadri et al[12]	1.3%	9.7%	7 (1-24)	7 (1-25)
Denoya et al[15]	Yes5	Yes5	19 ± 92	19 ± 92
Denost et al[10]	NR	NA	NR	NA
6Motson et al[7]	Yes6	NA	5 (0-14)	NA

¹Lymph node harvest reported as median (range) except

²where it is mean and

³where it is percent of patients with node count < or > 12;

⁴Authors define CRM as 2 mm; ³Authors report negative “radical” resection margins in all patients in discussion;

⁵CRM reported as Lap 1.17 ± 0.7; Open 0.96 ± 0.5;

⁶CRM reported as 5.5 mm (< 1-15 mm). NR: Not reported; NA: Not applicable; CRM: Circumferential resection margins.