Langenbecks Arch Surg DOI 10.1007/s00423-015-1281-3
ORIGINAL ARTICLE
Synchronous totally laparoscopic management of colorectal cancer and resectable liver metastases: a single center experience Stefano Berti & Elisa Francone & Michele Minuto & Pierfrancesco Bonfante & Carlo Sagnelli & Claudio Bianchi & Alessandra Tognoni & Emilio Falco
Received: 22 April 2014 / Accepted: 4 February 2015 # Springer-Verlag Berlin Heidelberg 2015
Abstract Purpose The simultaneous management of primary colorectal cancer and synchronous liver metastases has been reported extensively in open surgery. Data regarding feasibility, safety, and outcomes of the laparoscopic procedure is emerging from the experience of a few surgical centers. This paper aims at discussing the technique and results of a one-step laparoscopic approach for colorectal cancer and liver metastases resection on a series of 35 patients. Methods Between January 2008 and December 2013, 18 males and 17 females (median age 71 years) underwent colorectal and hepatic laparoscopic resection for colorectal metastatic cancer. Results Thirty-five colorectal resections and 66 liver resections were performed; no conversion to open surgery has been indicated. Median blood loss was 200 ml, median operative time 240 min, and median hospital stay was 8 days (range 4–30). According to Clavien-Dindo classification, two class II complications, two class IIIb complications, and one class IV complication were recorded. Two high-risk patients died within 30 days from surgery. S. Berti : E. Francone (*) : P. Bonfante : C. Sagnelli : C. Bianchi : E. Falco Department of Surgery, POLL–ASL 5, Via V. Veneto 197, 19100 La Spezia, Italy e-mail: [email protected] M. Minuto Department of Surgical Sciences (DISC), University of Genoa, Genoa, Italy M. Minuto Department of Surgery, Chirurgia 1 Unit, IRCCS AOU San Martino-IST, Genoa, Italy A. Tognoni Department of Oncology, POLL–ASL 5, La Spezia, Italy
Conclusions This series confirms the feasibility of synchronous laparoscopic colorectal and hepatic resections. To ensure the best outcomes, a careful selection of patients is needed. However, most patients can benefit from this surgical approach. Keywords Colorectal cancer . Liver metastases . Laparoscopic liver resection . Laparoscopic one-step procedure . Laparoscopic combined resection
Introduction Liver metastases (LM) are present at the time of diagnosis in up to 20 % of patients with colorectal cancer (CRC) [1, 2]. In these patients, surgery associated to neoadjuvant and/or adjuvant chemotherapy demonstrates an excellent survival rate [3–5]. The strategy of a Bone-step procedure^ (associating the hepatectomy to the colorectal resection) has demonstrated significant advantages in terms of lower postoperative complication rates, shorter hospital stay, and notable decrease in the global costs of treatment. This is also due to the elimination of a second surgical procedure necessary to treat metastases [1, 6–10]. From a strictly surgical point of view, laparoscopic surgery is now largely used in the treatment of CRC, and in the last decade, laparoscopic hepatectomies have been performed in many experienced centers. Abu Hilal et al. have analyzed the results obtained with the laparoscopic management of LM from CRC and concluded that a mini-invasive technique is not only feasible but also oncologically safe and effective [11–14]. Other authors obtained the same results in their series [1, 15–18]. These excellent results led a growing number of experienced laparoscopic surgeons to propose a one-step procedure
Langenbecks Arch Surg
for treating both the primary and the secondary in patients affected by metastatic CRC [9, 10, 19, 20], confirming not only the safety of this combined minimally invasive approach but also its advantages over the traditional open technique [21]. This single-step laparoscopic approach was started in our regional referral center for oncologic and laparoscopic surgery in 2008. This paper discusses the results obtained on a series of 35 patients undergoing synchronous colorectal and hepatic laparoscopic resection for CRC. Diagnosis and indications to surgery were achieved by submitting every patient to pancolonoscopy, computed tomography (CT) scan and magnetic resonance imaging (MRI).
Materials and methods Between January 2008 and December 2013 a total of 35 patients (18 males and 17 females) with a median age of 71 years (range 35–82) underwent a combined laparoscopic colorectal and liver resection for CRC with radiologic imaging of synchronous liver metastases. Over this period of time, two patients underwent an open right colectomy combined with right hepatectomy and segmentectomy of S4, S6, and S8, respectively. Prior to surgery, every surgical indication has been discussed in a multidisciplinary meeting, and only one patient, affected with low-rectal cancer, received neoadjuvant chemotherapy, according to the experts’ opinion. An R0-intended liver resection had been planned in 34 out of 35 patients, whereas one underwent a biopsy of the mass, to obtain a molecular typization of the tumor, and was therefore considered R2 resection. Patient selection for the laparoscopic resection of CRC and LM followed the criteria summarized by Morino [22], with some differences underlined in Table 1.
Table 1
Contraindications for the laparoscopic approach
Absolute contraindications
Relative contraindications
Performance status >2 Unresectable extrahepatic metastases
BMI >30 Need for major or complex (Louisville Class II) liver resections (GoR: C)
Perforated CRC
Extraperitoneal rectal cancer with difficult liver resections (GoR: C/D) Primary CRC >5 cm (GoR: D) R2 hepatic resections Previous open abdominal surgery
Modified from Morino and Famiglietti [22] BMI body mass index, CRC colorectal cancer, GoR grade of recommendation
Preoperatively, after the diagnosis of CRC was endoscopically obtained, liver function was assessed with blood evaluation of bilirubin, INR and albumin levels. CT scan was used to define loco-regional extension of the tumor, and to exclude extrahepatic disease. MRI was performed in selected cases to achieve a better characterization of both primary tumor and hepatic lesions. Thirty-four patients underwent elective treatment. One patient underwent an endoscopic stenting because of an obstructive cancer of the recto-sigmoidal junction that required urgent treatment, 10 days before the scheduled surgery. Four patients out of 35 (11.5 %) were preoperatively classified as ASA I, 15 (42.8 %) as ASA II, 14 (40 %) as ASA III, and 2 (5.7 %) as ASA IV. Colorectal resections consisted of ten right colectomies (two of which extended to the transverse colon), eight left colectomies, ten laparoscopic anterior resections (LAR) with partial mesorectal excision (PME), six laparoscopic low anterior resections (LLAR) with total mesorectal excision (TME), and one laparoscopic abdomino-perineal resection (LAPR). In this cohort of patients we performed 66 liver resections. According to Louisville classification [23], 17 class I and 18 class II resections were achieved. Types of surgery are summarized in Table 2. The overall morbidity, according to the Clavien-Dindo classification [24], is summarized in Table 3. Postoperatively, adjuvant chemotherapy was indicated after discussions among the experts. Surgical technique We will hereby describe only the technique used for the hepatectomy, since laparoscopic dissection of the large bowel is well standardized. Access to the abdomen was obtained using Hasson’s trocar under direct vision, either in right (for left sided lesions), or in left flank (for the right ones). Two 12-mm trocars were then positioned for colorectal resection. A third 12-mm trocar was used to perform the hepatectomy, and in 13 cases, a supplementary 5-mm trocar was used to ease the isolation of the hepatic pedicle, measure adopted in every patient in order to perform a Pringle manoeuvre in case of necessity. Once the peritoneum was entered and all the instruments were in place, the surgery on the large bowel was performed. This allows work on a healthy colic tissue, avoiding the venous congestion of the wall, that may be caused by Pringle manoeuvre performed in cases of difficult hepatic dissections. After the surgery on the colon/rectum, a laparoscopic ultrasound exploration of the entire liver was performed in every case, to allow a more precise definition of localization and extension of metastases, and to exactly establish the hepatic resection.
Sex
F M
F
F M F M
M
F F
F M M M F M M
F F
F M F
F
M
F
M
M F
1 2
3
4 5 6 7
8
9 10
11 12 13 14 15 16 17
18 19
20 21 22
23
24
25
26
27 28
59 75
82
76
76
80
81 78 62
68 66
78 65 71 78 65 71 58
74 63
71
78 58 35 71
81
48 76
Age
I II
III
III
IV
IV
III III II
II II
II II III III II II III
III II
III
III II I II
III
I II
ASA score
Low rectum Left colon
Sigmoid colon
Hepatic flexure locally advanced Cecum
Right colon
Left colon Left colon Sigmoid colon
Sigmoid colon Sigmoid colon
Cecum Cecum Sigmoid colon Hepatic flexure Rectal sigmoid junction Rectal sigmoid junction Rectal sigmoid junction
Sigmoid colon Left colon
Rectal sigmoid junction
Upper rectum Low rectum Rectal sigmoid junction Low rectum
Sigmoid colon Synchronous sigmoid and low rectum Transverse colon
Localization of T
Characteristics of the 35 patients and their surgeries
Number
Table 2
5 2-3-5-6
2-3
2-3
4b-5
5
3 4-6 5-8
4 3
6 3 7-8 1 4 5-8 4a-4b
5 4-5-8
3-4-7-8
5-7 4 2 3-5-7
4
2 3
Localization of M (segment)
Left colectomy according to Valdoni LLAR+ileostomy Left colectomy
Right colectomy+ cholecystectomy Right colectomy+ duodenal resection Right colectomy
Left colectomy LAR (+ ileostomy and ovariectomy) Left colectomy Left colectomy LLAR
Right colectomy Right colectomy LAR Right colectomy LAR LLAR LAR
LAR Left colectomy
LAR
Extended right colectomy LAR LLAR LAR LLAR
LLAR APR
Surgery of T
W.R. S5 W.R. S2+S3+S5+S6
W.R. S2+S3
Subsegmentectomy S4b+S5 en bloc W.R. S2+S3
W.R. S5
W.R. S3 W.R. S4b+S6 Subsegmentectomy S5+S8
W.R. S5 W.R. S4+S8 subsegmen tectomy S5 W.R. S6 W.R. S3 W.R. S7+S8 W.R. S1 W.R. S4b Subsegmentectomy S5+S8 W.R. S4b+subsegmen tectomy S4a+S2 W.R. S4b W.R. S3
W.R. S5+S7 W.R. S4a+S4b W.R. S2 Subsegmentectomy S3+S5+S7 (RF aided) W.R. S3+S4b+S7+S8
Subsegmentectomy S4
W.R. S2 W.R. S3
Surgery of M
No No
No
No
No
No
No No No
No No
No No No Yes No No No
No No
No
No No No Yes
Yes
No No
Pringle
Pfannenstiel Pfannenstiel
Pfannenstiel
Subumbilical
Left lower quadrant
Left lower quadrant
Pfannenstiel Pfannenstiel Pfannenstiel
Pfannenstiel Pfannenstiel
Right subcostal Right subcostal Suprainguinal left Right subcostal Suprainguinal left Pfannenstiel Pfannenstiel
Suprainguinal left Right subcostal
Suprainguinal left
Suprainguinal left Suprainguinal left Suprainguinal left Right subcostal
Right subcostal
Suprainguinal left Suprainguinal left
Specimen extraction site
350 420
230
220
295
180
225 320 240
180 220
120 120 240 220 240 310 285
180 180
240
250 240 180 450
255
120 165
Operation time (min)
220 240
200
200
350
200
200 250 800
150 200
300 150 300 500 70 1000 450
200 250
300
300 150 100 700
500
70 100
Blood loss (cc)
Langenbecks Arch Surg
ASA score American Society of Anesthesiologists score, WR Wedge resection, RF radio frequency, LAR laparoscopic anterior resection, LLAR laparoscopic low anterior resection, APR abdominal perineal resection, S hepatic segment
120 265 Subumbilical W.R. S3 M 35
82
II
Sigmoid colon
3
Left colectomy
No
160 200 140 200 100 310 345 275 320 210 Pfannenstiel Pfannenstiel Soprainguinal right Pfannenstiel Subumbilical F M M M F 30 31 32 33 34
76 74 79 64 81
III II III I III
Rectal sigmoid junction Left colon Right colon Cecum Rectum
3-4 2-4-5-6-7-8 5-7-8 3-4-5/7-6 2
LAR Left colectomy Right colectomy Right colectomy LAR
No No No Yes No
350 410 Pfannenstiel No
W.R. S3+S5+S6+S7+S8+RF for the lesion on the hilar plate W.R. S3+S4 W.R. S2+S4+S5+S6+S7+S8 W.R. S7+W.R. RF aided S5+S8 W.R. S3+S4+S5/7+S6 W.R. S2 Right colectomy M 29
60
II
Right colon
3-5-6-7-8+hilar plate
Surgery of M Age Sex Number
Table 2 (continued)
ASA score
Localization of T
Localization of M (segment)
Surgery of T
Pringle
Specimen extraction site
Operation time (min)
Blood loss (cc)
Langenbecks Arch Surg
After this evaluation, the lobe with the lesion(s) was completely mobilized by dissecting the suspending ligaments and exposing the posterior retroperitoneal surface of the liver. Hepatic wedge resections (WR) were then performed using Harmonic Scalpel (Ethicon Ultracision© harmonic scalpel, Johnson & Johnson Medical©), beginning with the incision of Glisson’s capsule, and then proceeding into the parenchyma surrounding the tumor, until its inferior plane was reached. Once the tumor had been removed, the resection margin was extensively coagulated, as an adjunctive attempt to obtain an oncologically radical dissection in cases of microscopic residual disease on the surgical bed. Pringle manoeuvre was necessary in only two particularly challenging resections of segments 7 and 8 respectively, out of the 66 performed. After dissection haemostasis was obtained using either wet bipolar cauterization or laparoscopic clips, when necessary. Finally, hepatic bed was always checked for biliary leaks and the breaches eventually secured with crossed stitches. At the end of the procedure, autologous fibrin glue was applied if needed. At the beginning of our experience, the extraction of the specimens was obtained through a transverse incision, omolateral to the colic resection (subcostal for right resections and supra-inguinal for left ones). In the last 14 cases, after performing the totally intracorporeal side-to-side intestinal anastomosis, a mini-Pfannenstiel was preferred, minimizing the possibility of incisional hernias.
Results All the procedures were performed entirely laparoscopically, with no patient needing a conversion to open surgery or to a video-assisted procedure. Median blood loss was 200 ml (range 70–1000), with a median operative time of 240 min (range 120–450) (Table 2). Median hospitalization was 8 days (range 4–30) (Table 3). The overall morbidity, according to Clavien-Dindo classification [24], is summarized in Table 3. Two class II complications (a pleural effusion and a central venous catheter infection, both successfully treated with antibiotics) and two class IIIb complications requiring a re-operation occurred. Among these latter ones, one patient who underwent an en bloc resection for locally advanced right colon cancer developed a duodenal fistula and required a laparoscopic duodenal wedge resection on fifth postoperative day; the other one underwent a laparoscopic adhesiolysis on seventh postoperative day because of an intestinal obstruction. One patient was struck by ictus cerebri on fifth postoperative day (class IV).
Tumor size–colon Tumor size–liver (cm) (cm) (range)
3 5 9
2.2 3.2 3.8
2 3 2.2
4 4.7 3.5 3.5 5.7 2.3 4.5 –
4 4.2 8 – 1 7
4.3
4
1.6 3.5 2.5 4.5
No. of cases
1 2 3
4 5 6
7 8 9
10 11 12 13 14 15 16 17
18 19 20 21 22 23
24
25
26 27 28 29
1.5 1–1.5 0.8–1.5 0.6–2
2.1
5.2
1 3.5 2 3.5–5 4 sclerotic nodule 4.5
2.7–4.7 2.2 angioma 1 0.5–1 5.5 6 8.5 4.3–6
1–1.2 2–4.2 2
0.7–1 3.2–4.5 0.4
3.7 7.5 6
Final histology and surgical outcome
Table 3
R0 R0 R0 R0
R0
R0
R0 R0 R0 R1 (focal invasion) – R0
R0 – R0 R1 (focal invasion) R0 R0 R0 R1 (focal invasion)
R0 R0 R2
R0 R0 R0
R1 (focal invasion) R0 R0
Resection status of liver metastases
2 3 3 3
3
4b
4a 3 3 3 2 3
3 3 3 4 3 3 4 3
3 3 3
3 4 3
3 3 3
0 0 1b 2a
1
1b
2b 1 1a 1 0 0
2 0 2 0 0 2 0 1
0 2 2
0 2 2
2 1 0
– 15 8 13
19
– 0.3 3.5 0.8 7
25
18 10 13 17 8 12
10 16 9 11 18 13 16 11
9 13 21
7 12 20
15 20 16
5.4
2 5.1 2.5 10 5 –
6.8 – – 4.5 – 5.5 11 4
0.3 3.3 7
2.7 4.2 4
4.7 – 3.2
No No No No No Acute coronary syndrome (deceased); class V according to CD Duodenal and biliary leakage; class IIIb according to CD CVC infection-fever; class II according to CD No No No No
No No Pleural effusion-fever; class II according to CD No No No No No No No No
No No MOF (deceased); class V according to CD No No No
T stage N stage DRM (cm) No. of LN Morbidity
2 2 3 2
2
5
3 2 4 2 3 2
2 2 2 2 2 4 4 4
2 4 2
6 3 2
2 2 4
7 8 9 6 7 19
8 4 5 7 9 6 6 6
9 7 11
7 7 6
6 5 16
Hospital stay(days)
3 3 3 3
2
8 8 9 7
8
NPT for 20 days 25
4 2 5 3 2 3
3 2 2 3 2 4 4 3
3 3 6
3 3 3
3 3 6
Flatus passing Diet start (days) (days)
Langenbecks Arch Surg
13 11 3 2.3 1b 0 3 4a 5 2.1 – 7.2
3.05 3 – 31 32 33
34 35
1a 0 2
9.6 10
13 12 8 3 2 3
R0 R0 S3 R1 (focal invasion) S4, S5/7, S6 R0 R0 R1 (focal invasion)
10 0
3.5–5 granulomatosis nodules 0.6–1.6 5 1.2–2.3 – 30
MOF multiorgan failure, LN lymph node, R resection margin, POD postoperative day, VLE exploration video laparoscopy, CD Clavien-Dindo classification, CVC central venous catheter, DRM distal bowel resection margin
9 16 4 4 3 3
30 7 22 – 4 4 – 3 2
14 4\11 4\9
Intestinal obstruction; class IIIb according to CD No No Ictus cerebri; class IV according to CD No No 3 –
7
T stage N stage DRM (cm) No. of LN Morbidity Resection status of liver metastases Tumor size–colon Tumor size–liver (cm) (cm) (range) No. of cases
Table 3 (continued)
Flatus passing Diet start (days) (days)
Hospital stay(days)
Langenbecks Arch Surg
Two patients (5.7 %) died in the immediate postoperative period: an 81-year-old ASA III patient, who underwent an extended right colectomy associated to S4 resection died for heart failure on 16th postoperative day, after several intermittent subocclusive episodes. The second patient, an 80-year-old ASA IV patient, who underwent a right colectomy and S5 wedge resection, died for massive myocardial infarction 10 days after discharge. Final histology demonstrated clear oncological margins in all colic specimens. Histologic results are summarized in Table 3. The examination of the large bowel revealed a T4 lesion in 6 patients (17.1 % of cases), a T3 lesion in 26 (74.3 %), and a T2 lesion in 3 (8.6 %). The median number of harvested lymph nodes was 13 (range 7–25), and the nodal status recorded was as follows: N0 in 14 patients (40 % of cases), N1 in 10 (28.6 %), and N2 in 11 (31.4 %). On the metastatic side, overall, 65 hepatic masses have been resected in 34 patients. Among those, final histology revealed a benign lesion in six cases: as a consequence, three patients were downstaged to M0 disease. Among the 59 resections for malignancy, a microscopic focal infiltration of the edges of the specimens was found in six cases (10.2 %): these cases were labeled as R1 (19.4 % of the patients). After surgery, a follow-up was available for 25 metastatic patients out of the 31 who were treated with a curative intent: three patients were excluded for the absence of metastatic disease, one because she underwent a bioptic resection (80.6 %). The median follow-up was 19 months (range 8– 55). Six patients (24 %) died for progressive disease after a mean and median follow-up of 25 and 19 months, respectively (range 8–51). Four patients are disease free at the last followup (16 %), all other patients (60 %) developed recurrent disease and are currently following further treatments. Among these latter ones, four were eligible for a second surgery that is described in Table 4. All the six patients with residual disease (R1) showed recurrent disease to the liver, one also developed a distant metastasis to the adrenal gland; one patient died for disease progression. Finally, after surgery, all patients received adjuvant systemic chemotherapy according to the oncologists’ indication with the following regimens: XELOX (80 %), FOLFOX 4 (20 %), and in 30 % of cases XELOX or FOLFOX 4 in association with bevacizumab.
Discussion Laparoscopic colorectal resections for the treatment of neoplasms of the large bowel are currently well standardized [25–27]. Over 20 % of patients diagnosed with CRC also have
Langenbecks Arch Surg Table 4
Patients who underwent a second surgery
Patient no.
First surgery
Second surgery
Months after first surgery
3 8 9 16
S4 subsegmentectomy S3, S4b, S7, and S8 wedge resections S5 wedge resection S5 and S8 subsegmentectomies
S6 subsegmentectomy Left lateral sectionectomy (open because of gastric infiltration) S6-7, S5-7, S1, and S4 wedge resections S2, S5, S6 segmentectomies (open)
24 11 24 12
metastatic liver disease that represents an indication to perform hepatectomy: it is therefore necessary to correctly plan the surgery on both the large bowel and the liver. The optimal timing for surgical resection for patients with synchronous CRC and LM has been a topic of debate, and at present it continues to evolve [2]. Currently, two different approaches to the disease are proposed in experienced centers: a staged procedure, which consists of two surgeries, performed either on the primary tumor or on its metastases first, and a one-stage procedure that allows an oncologically radical operation on the bowel and the liver at the same time [28–30]. A recent multicenter international analysis comparing simultaneous versus staged approaches found equivalent morbidity and mortality rate, as well as similar long-term outcomes [2]. Capussotti et al. demonstrated that staged procedures are burdened by a higher incidence of postoperative complications and longer hospitalization, when compared to the results obtained in patients undergoing simultaneous CRC surgery and hepatic resections [1]. Because laparoscopic approach is considered ideal for the treatment of CRC, a minimally invasive approach for both the primary tumor and its hepatic metastases has also been proposed. Several studies have already reported encouraging results on the feasibility and safety of the laparoscopic one-step procedure [2, 9, 18, 19]. The procedure shows the advantages of a minimally invasive approach, at the same time maintaining the standard therapeutic outcomes of traditional surgery [31–38]. Advantages of laparoscopic approach include a significantly better postoperative course that allows an earlier discharge from hospital, with faster return to normal activities, and also, less trauma to the abdominal wall resulting in a reduced incidence of incisional hernias. Despite the excellent results reported, there is still an ongoing debate over the indications and drawbacks of combined laparoscopic colorectal and hepatic resections, and a larger amount of data is needed to draw definitive conclusions. This report verifies two different issues: firstly, the outcome of a combined surgical approach on both the large bowel and the liver in patients affected with metastatic CRC, and secondly, the safety and efficacy of laparoscopic approach on the same patients.
In patients with CRC and metastatic disease to the liver, the policy is to perform the resection of primary tumor associated to parenchymal-sparing resection of metastatic disease to the liver whenever possible, thus reducing the risk of postoperative hepatic failure, while obtaining the same oncologic outcomes of extended hepatic resections. Moreover, laparoscopic hepatic resection allows to approach easily on the liver in case of reintervention. From a surgical point of view, we decided to limit our indications to those patients needing minor hepatic resections because a significant experience with minor resections is mandatory before approaching major hepatic resections laparoscopically. Our results confirm that this approach is successful, since all procedures were completed through an entirely laparoscopic approach. Analysing postoperative outcomes, we can observe that the incidence of morbidity did not differ from the one reported for traditional approach: that must be differently interpreted and discussed. The fact that a comparable incidence of morbidity was observed is the evidence of the safety of laparoscopic approach over conventional open procedure, given a surgical setting of experienced laparoscopic surgeons. A short comment is also necessary with regard to the hospitalization. In the interest of safety, the patients were hospitalized for the same amount of time as for conventional procedure. However, this policy is likely to be modified as the experience will grow. When dealing with the margins status, we have to discuss on our 19.4 % rate of patients (10.6 % of all resections) who did not reached an R0 resection. From a surgical point of view, an R1, Bby necessity,^ resection was purposely performed in cases where a lesion was close to a major vessel, to obtain a wedge resection avoiding to perform a segmentectomy. Moreover, in all cases, only a focal invasion was found, and this possibility is well known to surgeons. This is the main reason why the surgical bed has always been extensively necrotized after resection, with the aim to extend the margins of resection, even if we are aware that this strategy can be debatable. From the oncological side, De Haas and colleagues stated that Bthe contraindication of R1 resection should be revisited in the current era of effective chemotherapy because survival is similar that of R0 resection^ [39]. With this in mind, performing a resection with such a small extent of residual
Langenbecks Arch Surg
disease allows to consign to the oncologist appropriately cytoreducted patients. In terms of mortality, it is not possible to draw significant conclusions given both the small number of patients in our series and the absence of a control group of patients undergoing surgery through a conventional approach. It is nevertheless licit to presume that the two perioperative deaths would have been present also using a more conventional approach, given their high-risk preoperative conditions. An interesting clinical scenario occurred when a patient came to our attention in an emergency setting, with an obstructing IVA stage colorectal cancer. This situation is frequently encountered in a surgical department performing both elective and emergency surgery. Until recently, the only possible option for a patient presenting such a diagnosis was a staged procedure, consisting of up to three interventions (the creation of a diverting stoma, a delayed colorectal resection and, finally, the hepatic resection), and has always been considered an absolute contraindication to a simultaneous approach. This patient, affected by an obstructive disease, also showed the presence of a single metastasis of S2. It was therefore decided to proceed with colorectal stenting as a bridge to surgery. The patient underwent laparoscopic colic and hepatic resections in one stage 2 weeks later and was discharged from hospital on 6th post operative day, after an oncologically radical resection performed in one time. It can therefore be concluded that, in highly selected patients, a single-stage approach to treat colorectal cancer metastatic to the liver could be favored over the conventional two-stage procedures, given the comparable mortality and morbidity, as well as similar long-term outcomes [2], with evident advantages in terms of global costs for the Health System. In fact, it must be underscored the importance of aggressive tumor biology as independent predictor of poor survival - regardless to the applied technique - in the prognosis of these patients [2, 40]. A few comments should be spent to describe our attitude toward chemotherapy. Since the possibility of obtaining a radical resection is still a surgeon’s dependent factor, the decision to perform surgery was drawn when a liver metastasis was thought to be resectable with an acceptable morbidity, without indicating a debilitating therapy prior to surgery. This is in agreement with the oncologists, who received the patient after surgery with an oncologically adequate cytoreducted tumor. Our approach takes in account both the comparable rate of R1 resections in patients with or without chemotherapy [41] and the claimed chemotherapy systematic use postoperatively, remaining neoadjuvant chemotherapy for CRCLM a matter of debate [42]. In spite of the limited follow-up and the restricted number of patient analyzed in this study, which do not consent to draw definitive conclusions, the time of recurrence in our R1 group did not impact on overall survival rate, compared with data reported in other experiences [41, 42].
In terms of surgical approach, we are convinced that with the increasing experience, this minimally invasive technique might underline, in the near future, some significant advantages over the conventional approach in terms of both postoperative course and global costs obtaining, in the meantime, the same safety and oncologically radicality.
References 1. Capussotti L, Ferrero A, Vigano L et al (2007) Major liver resections synchronous with colorectal surgery. Ann Surg Oncol 14:195–201 2. Mayo SC, Pulitano C, Marques H et al (2013) Surgical management of patients with synchronous colorectal liver metastasis: a multicenter international analysis. J Am Coll Surg 216(4):707–716 3. Fernandez FG, Drebin JA, Linehan DC et al (2004) Five-year survival after resection of hepatic metastases from colorectal cancer in patients screened by positron emission tomography with F-18 fluorodeoxyglucose (FDG-PET). Ann Surg 240: 438–447 4. Tomlinson JS, Jarnagin WR, DeMatteo RP et al (2007) Actual 10year survival after resection of colorectal liver metastases defines cure. J Clin Oncol 25:4575–4580 5. Memon MA, Beckingham IJ (2001) Surgical resection of colorectal liver metastases. Color Dis 3:361–373 6. Tanaka K, Shimada H, Matsuo K et al (2004) Outcome after simultaneous colorectal and hepatic resection for colorectal cancer with synchronous metastases. Surgery 136:650–659 7. De Santibanes E, Lassalle FB, McCormack L et al (2002) Simultaneous colorectal and hepatic resections for colorectal cancer: postoperative and longterm outcomes. J Am Coll Surg 195:196–202 8. Weber JC, Bachellier P, Oussoultzoglou E, Jaeck D (2003) Simultaneous resection of colorectal primary tumour and synchronous liver metastases. Br J Surg 90:956–962 9. Zhang HZ, Dong SX, Zhou ZX et al (2007) Simultaneous liver and colorectal resection for synchronous colorectal liver metastasis. Zhonghua Wai Ke Za Zhi 45(13):902–904 10. Martin R, Paty P, Fong Y et al (2003) Simultaneous liver and colorectal resections are safe for synchronous colorectal liver metastasis. J Am Coll Surg 197(2):233–241 11. Abu Hilal M, Di Fabio F, Abu Salameh M, Pearce NW (2012) Oncological efficiency analysis of laparoscopic liver resection for primary and metastatic cancer: a single-center UK experience. Arch Surg 147(1):42–48 12. Abu Hilal M, Underwood T, Zuccaro M et al (2010) Short- and medium-term results of totally laparoscopic resection for colorectal liver metastases. Br J Surg 97(6):927–933 13. Abu Hilal M, Di Fabio F, Teng MJ et al (2011) Single-centre comparative study of laparoscopic versus open right hepatectomy. J Gastrointest Surg 15(5):818–823 14. Abu Hilal M, McPhail MJ, Zeidan B et al (2008) Laparoscopic versus open left lateral hepatic sectionectomy: a comparative study. Eur J Surg Oncol 34(12):1285–1288 15. Farges O, Jagot P, Kirstetter P et al (2002) Prospective assessment of the safety and benefit of laparoscopic liver resections. J Hepatobiliary Pancreatol Surg 9:242–248 16. Mala T, Edwin B, Gladhaug I et al (2002) A comparative study of the short-term outcome following open and laparoscopic liver resection of colorectal metastases. Surg Endosc 16:1059–1063
Langenbecks Arch Surg 17. Di Fabio F, Whistance R, Rahman S et al (2012) Exploring the role of laparoscopic surgery in two-stage hepatectomy for bilobar colorectal liver metastases. J Laparoendosc Adv Surg Tech A 22(7):647–650 18. Yin Z, Liu C, Chen Y et al (2013) Timing of hepatectomy in resectable synchronous colorectal liver metastases (SCRLM): simultaneous or delayed? Hepatology 57(6):2346–2357 19. Akiyoshi T, Kuroyanagi H, Saiura A et al (2009) Simultaneous resection of colorectal cancer and synchronous liver metastases: initial experience of laparoscopy for colorectal cancer resection. Dig Surg 26(6):471–475, Epub 2010 Jan 8 20. Nguyen KT, Laurent A, Dagher I et al (2009) Minimally invasive liver resection for metastatic colorectal cancer: a multi-institutional, international report of safety, feasibility, and early outcomes. Ann Surg 250(5):842–848 21. Huh JW, Koh YS, Kim HR et al (2011) Comparison of laparoscopic and open colorectal resections for patients undergoing simultaneous R0 resection for liver metastases. Surg Endosc 25(1):193–198 22. Morino M, Famiglietti F (2013) Minimally invasive combined surgery: liver and colon-rectum; minimally invasive surgery of the liver. Springer, Italy, pp 123–130 23. Buell JF, Cherqui D, Geller DA et al (2009) World Consensus Conference on Laparoscopic Surgery. The international position on laparoscopic liver surgery: The Louisville Statement, 2008. Ann Surg 250(5):825–830 24. Dindo D, Demartines N, Clavien PA (2004) Classification of surgical complications: a new proposal with evaluation in a cohort of 6336 patients and results of a survey. Ann Surg 240(2):205–213 25. Aziz O, Darzi AW (2008) Laparoscopic resection for colorectal cancer: evidence to date. Surg Oncol Clin N Am 17:519–531 26. Koopmann MC, Heise CP (2008) Laparoscopic and minimally invasive resection of malignant colorectal disease. Surg Clin North Am 88:1047–1072, vii 27. Phillips RK (ed)(2005) A companion to specialist surgical practice: colorectal surgery, 3rd edn. London: Elsevier Saunders 28. Viganò L, Langella S, Ferrero A et al (2013) Colorectal cancer with synchronous resectable liver metastases: monocentric management in a hepatobiliary referral center improves survival outcomes. Ann Surg Oncol 20(3):938–945 29. Fahy BN, Fischer CP (2012) Synchronous resection of colorectal primary and hepatic metastasis. J Gastrointest Oncol 3(1):48–58 30. Slesser AA, Simillis C, Goldin R et al (2013) A meta-analysis comparing simultaneous versus delayed resections in patients with synchronous colorectal liver metastases. Surg Oncol 22(1):36–47
31. Tranchart H, Diop PS, Lainas P et al (2011) Laparoscopic major hepatectomy can be safely performed with colorectal surgery for synchronous colorectal liver metastasis. HPB (Oxford) 13(1):46–50 32. Kim SH, Lim SB, Ha YH et al (2008) Laparoscopic-assisted combined colon and liver resection for primary colorectal cancer with synchronous liver metastases: initial experience. World J Surg 32(12):2701–2706 33. Hayashi M, Komeda K, Inoue Y et al (2011) Simultaneous laparoscopic resection of colorectal cancer and synchronous metastatic liver tumor. Int Surg 96(1):74–81 34. Lee JS, Hong HT, Kim JH et al (2010) Simultaneous laparoscopic resection of primary colorectal cancer and metastatic liver tumor: initial experience of single institute. J Laparoendosc Adv Surg Tech A 20(8):683–687 35. Casaccia M, Famiglietti F, Andorno E et al (2010) Simultaneous laparoscopic anterior resection and left hepatic lobectomy for stage IV rectal cancer. JSLS 14(3):414–417 36. Spampinato MG, Mandalá L, Quarta G et al (2013) One-stage, totally laparoscopic major hepatectomy and colectomy for colorectal neoplasm with synchronous liver metastasis: safety, feasibility and shortterm outcome. Surgery 153(6):861–865 37. Hatwell C, Bretagnol F, Farges O et al (2013) Laparoscopic resection of colorectal cancer facilitates simultaneous surgery of synchronous liver metastases. Color Dis 15(1):21–28 38. Lupinacci RM, Andraus W, De Paiva Haddad LB et al (2014) Simultaneous laparoscopic resection of primary colorectal cancer and associated liver metastases: a systematic review. Tech Coloproctol 18(2):129–135 39. De Haas RJ, Wicherts DA, Flores E et al (2008) R1 resection by necessity for colorectal liver metastases: is it still a contraindication to surgery? Ann Surg 248(4):626–637 40. Truant S, Sèquier C, Leteurtre E et al (2014) Tumor biology of colorectal liver metastases is a more important factor in survival than surgical margin clearance in the era of modern chemotherapy regimens. HPB (Oxford). doi:10.1111/hpb 12316 41. Ayez N, Lalmahomed ZS, Eggermont AM et al (2012) Outcome of microscopic incomplete resection (R1) of colorectal liver metastases in the era of neoadjuvant chemotherapy. Ann Surg Oncol 19(5): 1618–1627 42. Tranchart H, Chirica M, Faron M et al (2013) Prognostic impact of positive surgical margins after resection of colorectal cancer liver metastases: reappraisal in the era of modern chemotherapy. World J Surg 37(11):2647–2654
ORIGINAL ARTICLE
Synchronous totally laparoscopic management of colorectal cancer and resectable liver metastases: a single center experience Stefano Berti & Elisa Francone & Michele Minuto & Pierfrancesco Bonfante & Carlo Sagnelli & Claudio Bianchi & Alessandra Tognoni & Emilio Falco
Received: 22 April 2014 / Accepted: 4 February 2015 # Springer-Verlag Berlin Heidelberg 2015
Abstract Purpose The simultaneous management of primary colorectal cancer and synchronous liver metastases has been reported extensively in open surgery. Data regarding feasibility, safety, and outcomes of the laparoscopic procedure is emerging from the experience of a few surgical centers. This paper aims at discussing the technique and results of a one-step laparoscopic approach for colorectal cancer and liver metastases resection on a series of 35 patients. Methods Between January 2008 and December 2013, 18 males and 17 females (median age 71 years) underwent colorectal and hepatic laparoscopic resection for colorectal metastatic cancer. Results Thirty-five colorectal resections and 66 liver resections were performed; no conversion to open surgery has been indicated. Median blood loss was 200 ml, median operative time 240 min, and median hospital stay was 8 days (range 4–30). According to Clavien-Dindo classification, two class II complications, two class IIIb complications, and one class IV complication were recorded. Two high-risk patients died within 30 days from surgery. S. Berti : E. Francone (*) : P. Bonfante : C. Sagnelli : C. Bianchi : E. Falco Department of Surgery, POLL–ASL 5, Via V. Veneto 197, 19100 La Spezia, Italy e-mail: [email protected] M. Minuto Department of Surgical Sciences (DISC), University of Genoa, Genoa, Italy M. Minuto Department of Surgery, Chirurgia 1 Unit, IRCCS AOU San Martino-IST, Genoa, Italy A. Tognoni Department of Oncology, POLL–ASL 5, La Spezia, Italy
Conclusions This series confirms the feasibility of synchronous laparoscopic colorectal and hepatic resections. To ensure the best outcomes, a careful selection of patients is needed. However, most patients can benefit from this surgical approach. Keywords Colorectal cancer . Liver metastases . Laparoscopic liver resection . Laparoscopic one-step procedure . Laparoscopic combined resection
Introduction Liver metastases (LM) are present at the time of diagnosis in up to 20 % of patients with colorectal cancer (CRC) [1, 2]. In these patients, surgery associated to neoadjuvant and/or adjuvant chemotherapy demonstrates an excellent survival rate [3–5]. The strategy of a Bone-step procedure^ (associating the hepatectomy to the colorectal resection) has demonstrated significant advantages in terms of lower postoperative complication rates, shorter hospital stay, and notable decrease in the global costs of treatment. This is also due to the elimination of a second surgical procedure necessary to treat metastases [1, 6–10]. From a strictly surgical point of view, laparoscopic surgery is now largely used in the treatment of CRC, and in the last decade, laparoscopic hepatectomies have been performed in many experienced centers. Abu Hilal et al. have analyzed the results obtained with the laparoscopic management of LM from CRC and concluded that a mini-invasive technique is not only feasible but also oncologically safe and effective [11–14]. Other authors obtained the same results in their series [1, 15–18]. These excellent results led a growing number of experienced laparoscopic surgeons to propose a one-step procedure
Langenbecks Arch Surg
for treating both the primary and the secondary in patients affected by metastatic CRC [9, 10, 19, 20], confirming not only the safety of this combined minimally invasive approach but also its advantages over the traditional open technique [21]. This single-step laparoscopic approach was started in our regional referral center for oncologic and laparoscopic surgery in 2008. This paper discusses the results obtained on a series of 35 patients undergoing synchronous colorectal and hepatic laparoscopic resection for CRC. Diagnosis and indications to surgery were achieved by submitting every patient to pancolonoscopy, computed tomography (CT) scan and magnetic resonance imaging (MRI).
Materials and methods Between January 2008 and December 2013 a total of 35 patients (18 males and 17 females) with a median age of 71 years (range 35–82) underwent a combined laparoscopic colorectal and liver resection for CRC with radiologic imaging of synchronous liver metastases. Over this period of time, two patients underwent an open right colectomy combined with right hepatectomy and segmentectomy of S4, S6, and S8, respectively. Prior to surgery, every surgical indication has been discussed in a multidisciplinary meeting, and only one patient, affected with low-rectal cancer, received neoadjuvant chemotherapy, according to the experts’ opinion. An R0-intended liver resection had been planned in 34 out of 35 patients, whereas one underwent a biopsy of the mass, to obtain a molecular typization of the tumor, and was therefore considered R2 resection. Patient selection for the laparoscopic resection of CRC and LM followed the criteria summarized by Morino [22], with some differences underlined in Table 1.
Table 1
Contraindications for the laparoscopic approach
Absolute contraindications
Relative contraindications
Performance status >2 Unresectable extrahepatic metastases
BMI >30 Need for major or complex (Louisville Class II) liver resections (GoR: C)
Perforated CRC
Extraperitoneal rectal cancer with difficult liver resections (GoR: C/D) Primary CRC >5 cm (GoR: D) R2 hepatic resections Previous open abdominal surgery
Modified from Morino and Famiglietti [22] BMI body mass index, CRC colorectal cancer, GoR grade of recommendation
Preoperatively, after the diagnosis of CRC was endoscopically obtained, liver function was assessed with blood evaluation of bilirubin, INR and albumin levels. CT scan was used to define loco-regional extension of the tumor, and to exclude extrahepatic disease. MRI was performed in selected cases to achieve a better characterization of both primary tumor and hepatic lesions. Thirty-four patients underwent elective treatment. One patient underwent an endoscopic stenting because of an obstructive cancer of the recto-sigmoidal junction that required urgent treatment, 10 days before the scheduled surgery. Four patients out of 35 (11.5 %) were preoperatively classified as ASA I, 15 (42.8 %) as ASA II, 14 (40 %) as ASA III, and 2 (5.7 %) as ASA IV. Colorectal resections consisted of ten right colectomies (two of which extended to the transverse colon), eight left colectomies, ten laparoscopic anterior resections (LAR) with partial mesorectal excision (PME), six laparoscopic low anterior resections (LLAR) with total mesorectal excision (TME), and one laparoscopic abdomino-perineal resection (LAPR). In this cohort of patients we performed 66 liver resections. According to Louisville classification [23], 17 class I and 18 class II resections were achieved. Types of surgery are summarized in Table 2. The overall morbidity, according to the Clavien-Dindo classification [24], is summarized in Table 3. Postoperatively, adjuvant chemotherapy was indicated after discussions among the experts. Surgical technique We will hereby describe only the technique used for the hepatectomy, since laparoscopic dissection of the large bowel is well standardized. Access to the abdomen was obtained using Hasson’s trocar under direct vision, either in right (for left sided lesions), or in left flank (for the right ones). Two 12-mm trocars were then positioned for colorectal resection. A third 12-mm trocar was used to perform the hepatectomy, and in 13 cases, a supplementary 5-mm trocar was used to ease the isolation of the hepatic pedicle, measure adopted in every patient in order to perform a Pringle manoeuvre in case of necessity. Once the peritoneum was entered and all the instruments were in place, the surgery on the large bowel was performed. This allows work on a healthy colic tissue, avoiding the venous congestion of the wall, that may be caused by Pringle manoeuvre performed in cases of difficult hepatic dissections. After the surgery on the colon/rectum, a laparoscopic ultrasound exploration of the entire liver was performed in every case, to allow a more precise definition of localization and extension of metastases, and to exactly establish the hepatic resection.
Sex
F M
F
F M F M
M
F F
F M M M F M M
F F
F M F
F
M
F
M
M F
1 2
3
4 5 6 7
8
9 10
11 12 13 14 15 16 17
18 19
20 21 22
23
24
25
26
27 28
59 75
82
76
76
80
81 78 62
68 66
78 65 71 78 65 71 58
74 63
71
78 58 35 71
81
48 76
Age
I II
III
III
IV
IV
III III II
II II
II II III III II II III
III II
III
III II I II
III
I II
ASA score
Low rectum Left colon
Sigmoid colon
Hepatic flexure locally advanced Cecum
Right colon
Left colon Left colon Sigmoid colon
Sigmoid colon Sigmoid colon
Cecum Cecum Sigmoid colon Hepatic flexure Rectal sigmoid junction Rectal sigmoid junction Rectal sigmoid junction
Sigmoid colon Left colon
Rectal sigmoid junction
Upper rectum Low rectum Rectal sigmoid junction Low rectum
Sigmoid colon Synchronous sigmoid and low rectum Transverse colon
Localization of T
Characteristics of the 35 patients and their surgeries
Number
Table 2
5 2-3-5-6
2-3
2-3
4b-5
5
3 4-6 5-8
4 3
6 3 7-8 1 4 5-8 4a-4b
5 4-5-8
3-4-7-8
5-7 4 2 3-5-7
4
2 3
Localization of M (segment)
Left colectomy according to Valdoni LLAR+ileostomy Left colectomy
Right colectomy+ cholecystectomy Right colectomy+ duodenal resection Right colectomy
Left colectomy LAR (+ ileostomy and ovariectomy) Left colectomy Left colectomy LLAR
Right colectomy Right colectomy LAR Right colectomy LAR LLAR LAR
LAR Left colectomy
LAR
Extended right colectomy LAR LLAR LAR LLAR
LLAR APR
Surgery of T
W.R. S5 W.R. S2+S3+S5+S6
W.R. S2+S3
Subsegmentectomy S4b+S5 en bloc W.R. S2+S3
W.R. S5
W.R. S3 W.R. S4b+S6 Subsegmentectomy S5+S8
W.R. S5 W.R. S4+S8 subsegmen tectomy S5 W.R. S6 W.R. S3 W.R. S7+S8 W.R. S1 W.R. S4b Subsegmentectomy S5+S8 W.R. S4b+subsegmen tectomy S4a+S2 W.R. S4b W.R. S3
W.R. S5+S7 W.R. S4a+S4b W.R. S2 Subsegmentectomy S3+S5+S7 (RF aided) W.R. S3+S4b+S7+S8
Subsegmentectomy S4
W.R. S2 W.R. S3
Surgery of M
No No
No
No
No
No
No No No
No No
No No No Yes No No No
No No
No
No No No Yes
Yes
No No
Pringle
Pfannenstiel Pfannenstiel
Pfannenstiel
Subumbilical
Left lower quadrant
Left lower quadrant
Pfannenstiel Pfannenstiel Pfannenstiel
Pfannenstiel Pfannenstiel
Right subcostal Right subcostal Suprainguinal left Right subcostal Suprainguinal left Pfannenstiel Pfannenstiel
Suprainguinal left Right subcostal
Suprainguinal left
Suprainguinal left Suprainguinal left Suprainguinal left Right subcostal
Right subcostal
Suprainguinal left Suprainguinal left
Specimen extraction site
350 420
230
220
295
180
225 320 240
180 220
120 120 240 220 240 310 285
180 180
240
250 240 180 450
255
120 165
Operation time (min)
220 240
200
200
350
200
200 250 800
150 200
300 150 300 500 70 1000 450
200 250
300
300 150 100 700
500
70 100
Blood loss (cc)
Langenbecks Arch Surg
ASA score American Society of Anesthesiologists score, WR Wedge resection, RF radio frequency, LAR laparoscopic anterior resection, LLAR laparoscopic low anterior resection, APR abdominal perineal resection, S hepatic segment
120 265 Subumbilical W.R. S3 M 35
82
II
Sigmoid colon
3
Left colectomy
No
160 200 140 200 100 310 345 275 320 210 Pfannenstiel Pfannenstiel Soprainguinal right Pfannenstiel Subumbilical F M M M F 30 31 32 33 34
76 74 79 64 81
III II III I III
Rectal sigmoid junction Left colon Right colon Cecum Rectum
3-4 2-4-5-6-7-8 5-7-8 3-4-5/7-6 2
LAR Left colectomy Right colectomy Right colectomy LAR
No No No Yes No
350 410 Pfannenstiel No
W.R. S3+S5+S6+S7+S8+RF for the lesion on the hilar plate W.R. S3+S4 W.R. S2+S4+S5+S6+S7+S8 W.R. S7+W.R. RF aided S5+S8 W.R. S3+S4+S5/7+S6 W.R. S2 Right colectomy M 29
60
II
Right colon
3-5-6-7-8+hilar plate
Surgery of M Age Sex Number
Table 2 (continued)
ASA score
Localization of T
Localization of M (segment)
Surgery of T
Pringle
Specimen extraction site
Operation time (min)
Blood loss (cc)
Langenbecks Arch Surg
After this evaluation, the lobe with the lesion(s) was completely mobilized by dissecting the suspending ligaments and exposing the posterior retroperitoneal surface of the liver. Hepatic wedge resections (WR) were then performed using Harmonic Scalpel (Ethicon Ultracision© harmonic scalpel, Johnson & Johnson Medical©), beginning with the incision of Glisson’s capsule, and then proceeding into the parenchyma surrounding the tumor, until its inferior plane was reached. Once the tumor had been removed, the resection margin was extensively coagulated, as an adjunctive attempt to obtain an oncologically radical dissection in cases of microscopic residual disease on the surgical bed. Pringle manoeuvre was necessary in only two particularly challenging resections of segments 7 and 8 respectively, out of the 66 performed. After dissection haemostasis was obtained using either wet bipolar cauterization or laparoscopic clips, when necessary. Finally, hepatic bed was always checked for biliary leaks and the breaches eventually secured with crossed stitches. At the end of the procedure, autologous fibrin glue was applied if needed. At the beginning of our experience, the extraction of the specimens was obtained through a transverse incision, omolateral to the colic resection (subcostal for right resections and supra-inguinal for left ones). In the last 14 cases, after performing the totally intracorporeal side-to-side intestinal anastomosis, a mini-Pfannenstiel was preferred, minimizing the possibility of incisional hernias.
Results All the procedures were performed entirely laparoscopically, with no patient needing a conversion to open surgery or to a video-assisted procedure. Median blood loss was 200 ml (range 70–1000), with a median operative time of 240 min (range 120–450) (Table 2). Median hospitalization was 8 days (range 4–30) (Table 3). The overall morbidity, according to Clavien-Dindo classification [24], is summarized in Table 3. Two class II complications (a pleural effusion and a central venous catheter infection, both successfully treated with antibiotics) and two class IIIb complications requiring a re-operation occurred. Among these latter ones, one patient who underwent an en bloc resection for locally advanced right colon cancer developed a duodenal fistula and required a laparoscopic duodenal wedge resection on fifth postoperative day; the other one underwent a laparoscopic adhesiolysis on seventh postoperative day because of an intestinal obstruction. One patient was struck by ictus cerebri on fifth postoperative day (class IV).
Tumor size–colon Tumor size–liver (cm) (cm) (range)
3 5 9
2.2 3.2 3.8
2 3 2.2
4 4.7 3.5 3.5 5.7 2.3 4.5 –
4 4.2 8 – 1 7
4.3
4
1.6 3.5 2.5 4.5
No. of cases
1 2 3
4 5 6
7 8 9
10 11 12 13 14 15 16 17
18 19 20 21 22 23
24
25
26 27 28 29
1.5 1–1.5 0.8–1.5 0.6–2
2.1
5.2
1 3.5 2 3.5–5 4 sclerotic nodule 4.5
2.7–4.7 2.2 angioma 1 0.5–1 5.5 6 8.5 4.3–6
1–1.2 2–4.2 2
0.7–1 3.2–4.5 0.4
3.7 7.5 6
Final histology and surgical outcome
Table 3
R0 R0 R0 R0
R0
R0
R0 R0 R0 R1 (focal invasion) – R0
R0 – R0 R1 (focal invasion) R0 R0 R0 R1 (focal invasion)
R0 R0 R2
R0 R0 R0
R1 (focal invasion) R0 R0
Resection status of liver metastases
2 3 3 3
3
4b
4a 3 3 3 2 3
3 3 3 4 3 3 4 3
3 3 3
3 4 3
3 3 3
0 0 1b 2a
1
1b
2b 1 1a 1 0 0
2 0 2 0 0 2 0 1
0 2 2
0 2 2
2 1 0
– 15 8 13
19
– 0.3 3.5 0.8 7
25
18 10 13 17 8 12
10 16 9 11 18 13 16 11
9 13 21
7 12 20
15 20 16
5.4
2 5.1 2.5 10 5 –
6.8 – – 4.5 – 5.5 11 4
0.3 3.3 7
2.7 4.2 4
4.7 – 3.2
No No No No No Acute coronary syndrome (deceased); class V according to CD Duodenal and biliary leakage; class IIIb according to CD CVC infection-fever; class II according to CD No No No No
No No Pleural effusion-fever; class II according to CD No No No No No No No No
No No MOF (deceased); class V according to CD No No No
T stage N stage DRM (cm) No. of LN Morbidity
2 2 3 2
2
5
3 2 4 2 3 2
2 2 2 2 2 4 4 4
2 4 2
6 3 2
2 2 4
7 8 9 6 7 19
8 4 5 7 9 6 6 6
9 7 11
7 7 6
6 5 16
Hospital stay(days)
3 3 3 3
2
8 8 9 7
8
NPT for 20 days 25
4 2 5 3 2 3
3 2 2 3 2 4 4 3
3 3 6
3 3 3
3 3 6
Flatus passing Diet start (days) (days)
Langenbecks Arch Surg
13 11 3 2.3 1b 0 3 4a 5 2.1 – 7.2
3.05 3 – 31 32 33
34 35
1a 0 2
9.6 10
13 12 8 3 2 3
R0 R0 S3 R1 (focal invasion) S4, S5/7, S6 R0 R0 R1 (focal invasion)
10 0
3.5–5 granulomatosis nodules 0.6–1.6 5 1.2–2.3 – 30
MOF multiorgan failure, LN lymph node, R resection margin, POD postoperative day, VLE exploration video laparoscopy, CD Clavien-Dindo classification, CVC central venous catheter, DRM distal bowel resection margin
9 16 4 4 3 3
30 7 22 – 4 4 – 3 2
14 4\11 4\9
Intestinal obstruction; class IIIb according to CD No No Ictus cerebri; class IV according to CD No No 3 –
7
T stage N stage DRM (cm) No. of LN Morbidity Resection status of liver metastases Tumor size–colon Tumor size–liver (cm) (cm) (range) No. of cases
Table 3 (continued)
Flatus passing Diet start (days) (days)
Hospital stay(days)
Langenbecks Arch Surg
Two patients (5.7 %) died in the immediate postoperative period: an 81-year-old ASA III patient, who underwent an extended right colectomy associated to S4 resection died for heart failure on 16th postoperative day, after several intermittent subocclusive episodes. The second patient, an 80-year-old ASA IV patient, who underwent a right colectomy and S5 wedge resection, died for massive myocardial infarction 10 days after discharge. Final histology demonstrated clear oncological margins in all colic specimens. Histologic results are summarized in Table 3. The examination of the large bowel revealed a T4 lesion in 6 patients (17.1 % of cases), a T3 lesion in 26 (74.3 %), and a T2 lesion in 3 (8.6 %). The median number of harvested lymph nodes was 13 (range 7–25), and the nodal status recorded was as follows: N0 in 14 patients (40 % of cases), N1 in 10 (28.6 %), and N2 in 11 (31.4 %). On the metastatic side, overall, 65 hepatic masses have been resected in 34 patients. Among those, final histology revealed a benign lesion in six cases: as a consequence, three patients were downstaged to M0 disease. Among the 59 resections for malignancy, a microscopic focal infiltration of the edges of the specimens was found in six cases (10.2 %): these cases were labeled as R1 (19.4 % of the patients). After surgery, a follow-up was available for 25 metastatic patients out of the 31 who were treated with a curative intent: three patients were excluded for the absence of metastatic disease, one because she underwent a bioptic resection (80.6 %). The median follow-up was 19 months (range 8– 55). Six patients (24 %) died for progressive disease after a mean and median follow-up of 25 and 19 months, respectively (range 8–51). Four patients are disease free at the last followup (16 %), all other patients (60 %) developed recurrent disease and are currently following further treatments. Among these latter ones, four were eligible for a second surgery that is described in Table 4. All the six patients with residual disease (R1) showed recurrent disease to the liver, one also developed a distant metastasis to the adrenal gland; one patient died for disease progression. Finally, after surgery, all patients received adjuvant systemic chemotherapy according to the oncologists’ indication with the following regimens: XELOX (80 %), FOLFOX 4 (20 %), and in 30 % of cases XELOX or FOLFOX 4 in association with bevacizumab.
Discussion Laparoscopic colorectal resections for the treatment of neoplasms of the large bowel are currently well standardized [25–27]. Over 20 % of patients diagnosed with CRC also have
Langenbecks Arch Surg Table 4
Patients who underwent a second surgery
Patient no.
First surgery
Second surgery
Months after first surgery
3 8 9 16
S4 subsegmentectomy S3, S4b, S7, and S8 wedge resections S5 wedge resection S5 and S8 subsegmentectomies
S6 subsegmentectomy Left lateral sectionectomy (open because of gastric infiltration) S6-7, S5-7, S1, and S4 wedge resections S2, S5, S6 segmentectomies (open)
24 11 24 12
metastatic liver disease that represents an indication to perform hepatectomy: it is therefore necessary to correctly plan the surgery on both the large bowel and the liver. The optimal timing for surgical resection for patients with synchronous CRC and LM has been a topic of debate, and at present it continues to evolve [2]. Currently, two different approaches to the disease are proposed in experienced centers: a staged procedure, which consists of two surgeries, performed either on the primary tumor or on its metastases first, and a one-stage procedure that allows an oncologically radical operation on the bowel and the liver at the same time [28–30]. A recent multicenter international analysis comparing simultaneous versus staged approaches found equivalent morbidity and mortality rate, as well as similar long-term outcomes [2]. Capussotti et al. demonstrated that staged procedures are burdened by a higher incidence of postoperative complications and longer hospitalization, when compared to the results obtained in patients undergoing simultaneous CRC surgery and hepatic resections [1]. Because laparoscopic approach is considered ideal for the treatment of CRC, a minimally invasive approach for both the primary tumor and its hepatic metastases has also been proposed. Several studies have already reported encouraging results on the feasibility and safety of the laparoscopic one-step procedure [2, 9, 18, 19]. The procedure shows the advantages of a minimally invasive approach, at the same time maintaining the standard therapeutic outcomes of traditional surgery [31–38]. Advantages of laparoscopic approach include a significantly better postoperative course that allows an earlier discharge from hospital, with faster return to normal activities, and also, less trauma to the abdominal wall resulting in a reduced incidence of incisional hernias. Despite the excellent results reported, there is still an ongoing debate over the indications and drawbacks of combined laparoscopic colorectal and hepatic resections, and a larger amount of data is needed to draw definitive conclusions. This report verifies two different issues: firstly, the outcome of a combined surgical approach on both the large bowel and the liver in patients affected with metastatic CRC, and secondly, the safety and efficacy of laparoscopic approach on the same patients.
In patients with CRC and metastatic disease to the liver, the policy is to perform the resection of primary tumor associated to parenchymal-sparing resection of metastatic disease to the liver whenever possible, thus reducing the risk of postoperative hepatic failure, while obtaining the same oncologic outcomes of extended hepatic resections. Moreover, laparoscopic hepatic resection allows to approach easily on the liver in case of reintervention. From a surgical point of view, we decided to limit our indications to those patients needing minor hepatic resections because a significant experience with minor resections is mandatory before approaching major hepatic resections laparoscopically. Our results confirm that this approach is successful, since all procedures were completed through an entirely laparoscopic approach. Analysing postoperative outcomes, we can observe that the incidence of morbidity did not differ from the one reported for traditional approach: that must be differently interpreted and discussed. The fact that a comparable incidence of morbidity was observed is the evidence of the safety of laparoscopic approach over conventional open procedure, given a surgical setting of experienced laparoscopic surgeons. A short comment is also necessary with regard to the hospitalization. In the interest of safety, the patients were hospitalized for the same amount of time as for conventional procedure. However, this policy is likely to be modified as the experience will grow. When dealing with the margins status, we have to discuss on our 19.4 % rate of patients (10.6 % of all resections) who did not reached an R0 resection. From a surgical point of view, an R1, Bby necessity,^ resection was purposely performed in cases where a lesion was close to a major vessel, to obtain a wedge resection avoiding to perform a segmentectomy. Moreover, in all cases, only a focal invasion was found, and this possibility is well known to surgeons. This is the main reason why the surgical bed has always been extensively necrotized after resection, with the aim to extend the margins of resection, even if we are aware that this strategy can be debatable. From the oncological side, De Haas and colleagues stated that Bthe contraindication of R1 resection should be revisited in the current era of effective chemotherapy because survival is similar that of R0 resection^ [39]. With this in mind, performing a resection with such a small extent of residual
Langenbecks Arch Surg
disease allows to consign to the oncologist appropriately cytoreducted patients. In terms of mortality, it is not possible to draw significant conclusions given both the small number of patients in our series and the absence of a control group of patients undergoing surgery through a conventional approach. It is nevertheless licit to presume that the two perioperative deaths would have been present also using a more conventional approach, given their high-risk preoperative conditions. An interesting clinical scenario occurred when a patient came to our attention in an emergency setting, with an obstructing IVA stage colorectal cancer. This situation is frequently encountered in a surgical department performing both elective and emergency surgery. Until recently, the only possible option for a patient presenting such a diagnosis was a staged procedure, consisting of up to three interventions (the creation of a diverting stoma, a delayed colorectal resection and, finally, the hepatic resection), and has always been considered an absolute contraindication to a simultaneous approach. This patient, affected by an obstructive disease, also showed the presence of a single metastasis of S2. It was therefore decided to proceed with colorectal stenting as a bridge to surgery. The patient underwent laparoscopic colic and hepatic resections in one stage 2 weeks later and was discharged from hospital on 6th post operative day, after an oncologically radical resection performed in one time. It can therefore be concluded that, in highly selected patients, a single-stage approach to treat colorectal cancer metastatic to the liver could be favored over the conventional two-stage procedures, given the comparable mortality and morbidity, as well as similar long-term outcomes [2], with evident advantages in terms of global costs for the Health System. In fact, it must be underscored the importance of aggressive tumor biology as independent predictor of poor survival - regardless to the applied technique - in the prognosis of these patients [2, 40]. A few comments should be spent to describe our attitude toward chemotherapy. Since the possibility of obtaining a radical resection is still a surgeon’s dependent factor, the decision to perform surgery was drawn when a liver metastasis was thought to be resectable with an acceptable morbidity, without indicating a debilitating therapy prior to surgery. This is in agreement with the oncologists, who received the patient after surgery with an oncologically adequate cytoreducted tumor. Our approach takes in account both the comparable rate of R1 resections in patients with or without chemotherapy [41] and the claimed chemotherapy systematic use postoperatively, remaining neoadjuvant chemotherapy for CRCLM a matter of debate [42]. In spite of the limited follow-up and the restricted number of patient analyzed in this study, which do not consent to draw definitive conclusions, the time of recurrence in our R1 group did not impact on overall survival rate, compared with data reported in other experiences [41, 42].
In terms of surgical approach, we are convinced that with the increasing experience, this minimally invasive technique might underline, in the near future, some significant advantages over the conventional approach in terms of both postoperative course and global costs obtaining, in the meantime, the same safety and oncologically radicality.
References 1. Capussotti L, Ferrero A, Vigano L et al (2007) Major liver resections synchronous with colorectal surgery. Ann Surg Oncol 14:195–201 2. Mayo SC, Pulitano C, Marques H et al (2013) Surgical management of patients with synchronous colorectal liver metastasis: a multicenter international analysis. J Am Coll Surg 216(4):707–716 3. Fernandez FG, Drebin JA, Linehan DC et al (2004) Five-year survival after resection of hepatic metastases from colorectal cancer in patients screened by positron emission tomography with F-18 fluorodeoxyglucose (FDG-PET). Ann Surg 240: 438–447 4. Tomlinson JS, Jarnagin WR, DeMatteo RP et al (2007) Actual 10year survival after resection of colorectal liver metastases defines cure. J Clin Oncol 25:4575–4580 5. Memon MA, Beckingham IJ (2001) Surgical resection of colorectal liver metastases. Color Dis 3:361–373 6. Tanaka K, Shimada H, Matsuo K et al (2004) Outcome after simultaneous colorectal and hepatic resection for colorectal cancer with synchronous metastases. Surgery 136:650–659 7. De Santibanes E, Lassalle FB, McCormack L et al (2002) Simultaneous colorectal and hepatic resections for colorectal cancer: postoperative and longterm outcomes. J Am Coll Surg 195:196–202 8. Weber JC, Bachellier P, Oussoultzoglou E, Jaeck D (2003) Simultaneous resection of colorectal primary tumour and synchronous liver metastases. Br J Surg 90:956–962 9. Zhang HZ, Dong SX, Zhou ZX et al (2007) Simultaneous liver and colorectal resection for synchronous colorectal liver metastasis. Zhonghua Wai Ke Za Zhi 45(13):902–904 10. Martin R, Paty P, Fong Y et al (2003) Simultaneous liver and colorectal resections are safe for synchronous colorectal liver metastasis. J Am Coll Surg 197(2):233–241 11. Abu Hilal M, Di Fabio F, Abu Salameh M, Pearce NW (2012) Oncological efficiency analysis of laparoscopic liver resection for primary and metastatic cancer: a single-center UK experience. Arch Surg 147(1):42–48 12. Abu Hilal M, Underwood T, Zuccaro M et al (2010) Short- and medium-term results of totally laparoscopic resection for colorectal liver metastases. Br J Surg 97(6):927–933 13. Abu Hilal M, Di Fabio F, Teng MJ et al (2011) Single-centre comparative study of laparoscopic versus open right hepatectomy. J Gastrointest Surg 15(5):818–823 14. Abu Hilal M, McPhail MJ, Zeidan B et al (2008) Laparoscopic versus open left lateral hepatic sectionectomy: a comparative study. Eur J Surg Oncol 34(12):1285–1288 15. Farges O, Jagot P, Kirstetter P et al (2002) Prospective assessment of the safety and benefit of laparoscopic liver resections. J Hepatobiliary Pancreatol Surg 9:242–248 16. Mala T, Edwin B, Gladhaug I et al (2002) A comparative study of the short-term outcome following open and laparoscopic liver resection of colorectal metastases. Surg Endosc 16:1059–1063
Langenbecks Arch Surg 17. Di Fabio F, Whistance R, Rahman S et al (2012) Exploring the role of laparoscopic surgery in two-stage hepatectomy for bilobar colorectal liver metastases. J Laparoendosc Adv Surg Tech A 22(7):647–650 18. Yin Z, Liu C, Chen Y et al (2013) Timing of hepatectomy in resectable synchronous colorectal liver metastases (SCRLM): simultaneous or delayed? Hepatology 57(6):2346–2357 19. Akiyoshi T, Kuroyanagi H, Saiura A et al (2009) Simultaneous resection of colorectal cancer and synchronous liver metastases: initial experience of laparoscopy for colorectal cancer resection. Dig Surg 26(6):471–475, Epub 2010 Jan 8 20. Nguyen KT, Laurent A, Dagher I et al (2009) Minimally invasive liver resection for metastatic colorectal cancer: a multi-institutional, international report of safety, feasibility, and early outcomes. Ann Surg 250(5):842–848 21. Huh JW, Koh YS, Kim HR et al (2011) Comparison of laparoscopic and open colorectal resections for patients undergoing simultaneous R0 resection for liver metastases. Surg Endosc 25(1):193–198 22. Morino M, Famiglietti F (2013) Minimally invasive combined surgery: liver and colon-rectum; minimally invasive surgery of the liver. Springer, Italy, pp 123–130 23. Buell JF, Cherqui D, Geller DA et al (2009) World Consensus Conference on Laparoscopic Surgery. The international position on laparoscopic liver surgery: The Louisville Statement, 2008. Ann Surg 250(5):825–830 24. Dindo D, Demartines N, Clavien PA (2004) Classification of surgical complications: a new proposal with evaluation in a cohort of 6336 patients and results of a survey. Ann Surg 240(2):205–213 25. Aziz O, Darzi AW (2008) Laparoscopic resection for colorectal cancer: evidence to date. Surg Oncol Clin N Am 17:519–531 26. Koopmann MC, Heise CP (2008) Laparoscopic and minimally invasive resection of malignant colorectal disease. Surg Clin North Am 88:1047–1072, vii 27. Phillips RK (ed)(2005) A companion to specialist surgical practice: colorectal surgery, 3rd edn. London: Elsevier Saunders 28. Viganò L, Langella S, Ferrero A et al (2013) Colorectal cancer with synchronous resectable liver metastases: monocentric management in a hepatobiliary referral center improves survival outcomes. Ann Surg Oncol 20(3):938–945 29. Fahy BN, Fischer CP (2012) Synchronous resection of colorectal primary and hepatic metastasis. J Gastrointest Oncol 3(1):48–58 30. Slesser AA, Simillis C, Goldin R et al (2013) A meta-analysis comparing simultaneous versus delayed resections in patients with synchronous colorectal liver metastases. Surg Oncol 22(1):36–47
31. Tranchart H, Diop PS, Lainas P et al (2011) Laparoscopic major hepatectomy can be safely performed with colorectal surgery for synchronous colorectal liver metastasis. HPB (Oxford) 13(1):46–50 32. Kim SH, Lim SB, Ha YH et al (2008) Laparoscopic-assisted combined colon and liver resection for primary colorectal cancer with synchronous liver metastases: initial experience. World J Surg 32(12):2701–2706 33. Hayashi M, Komeda K, Inoue Y et al (2011) Simultaneous laparoscopic resection of colorectal cancer and synchronous metastatic liver tumor. Int Surg 96(1):74–81 34. Lee JS, Hong HT, Kim JH et al (2010) Simultaneous laparoscopic resection of primary colorectal cancer and metastatic liver tumor: initial experience of single institute. J Laparoendosc Adv Surg Tech A 20(8):683–687 35. Casaccia M, Famiglietti F, Andorno E et al (2010) Simultaneous laparoscopic anterior resection and left hepatic lobectomy for stage IV rectal cancer. JSLS 14(3):414–417 36. Spampinato MG, Mandalá L, Quarta G et al (2013) One-stage, totally laparoscopic major hepatectomy and colectomy for colorectal neoplasm with synchronous liver metastasis: safety, feasibility and shortterm outcome. Surgery 153(6):861–865 37. Hatwell C, Bretagnol F, Farges O et al (2013) Laparoscopic resection of colorectal cancer facilitates simultaneous surgery of synchronous liver metastases. Color Dis 15(1):21–28 38. Lupinacci RM, Andraus W, De Paiva Haddad LB et al (2014) Simultaneous laparoscopic resection of primary colorectal cancer and associated liver metastases: a systematic review. Tech Coloproctol 18(2):129–135 39. De Haas RJ, Wicherts DA, Flores E et al (2008) R1 resection by necessity for colorectal liver metastases: is it still a contraindication to surgery? Ann Surg 248(4):626–637 40. Truant S, Sèquier C, Leteurtre E et al (2014) Tumor biology of colorectal liver metastases is a more important factor in survival than surgical margin clearance in the era of modern chemotherapy regimens. HPB (Oxford). doi:10.1111/hpb 12316 41. Ayez N, Lalmahomed ZS, Eggermont AM et al (2012) Outcome of microscopic incomplete resection (R1) of colorectal liver metastases in the era of neoadjuvant chemotherapy. Ann Surg Oncol 19(5): 1618–1627 42. Tranchart H, Chirica M, Faron M et al (2013) Prognostic impact of positive surgical margins after resection of colorectal cancer liver metastases: reappraisal in the era of modern chemotherapy. World J Surg 37(11):2647–2654
