Oncological outcome after laparoscopic ‘no-touch’ versus ‘touch’ left pancreatectomy for pancreatic adenocarcinoma

doi:10.21203/rs.3.rs-2105153/v1

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Oncological outcome after laparoscopic ‘no-touch’ versus ‘touch’ left pancreatectomy for pancreatic adenocarcinoma

https://doi.org/10.21203/rs.3.rs-2105153/v1

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Background: The validity of laparoscopic distal pancreatectomy in left-sided pancreatic adenocarcinoma (PDAC) is still unclear. However, a meticulous surgical dissection through a “no-touch” technique might allow a radical oncological resection with minimal risk of tumor dissemination and seeding. This study aims to evaluate the oncological outcomes of the laparoscopic “no touch” technique versus the “touch” technique

Methods: From 2001 to 2020, we analyzed retrospectively 45 patients undergoing LDP (laparoscopic distal pancreatectomy) for PDAC from two centers. Factors associated with overall (OS), disease-free (DFS) survival and Time to recurrence (TTR) were identified.

Results. The OS rates in the ‘no-touch’ and ‘touch’ groups were 95% vs 78% (1-year OS); 50% vs 50% (3-year OS), respectively (p=0.60). The DFS rates in the ‘no-touch’ and ‘touch’ groups were 72 % vs 57 % (1-year DFS); 32% vs 28 % (3-year DFS), respectively (p=0.11). The TTR rates in the ‘no-touch’ and ‘touch’ groups were 77 % vs 61 % (1-year TTR); 54% vs 30 % (3-year TTR); 46% vs 11 % (5-year TTR); respectively (p=0.02) In multivariate analysis the only factors were Touch technique (OR= 2.62, p= 0.02) and lymphovascular emboli (OR= 4.8; p=0.002).

Conclusion. We advise the ‘no-touch’ technique in patients with resectable PDAC in the pancreatic body and tail. Although this study does not provide definitive proof of superiority, no apparent downsides are present for the ‘no-touch’ technique in this setting although there could be oncological benefits.

Laparoscopic

pancreas adenocarcinoma

outcome

survival

oncology

In 30% of patients, pancreatic ductal adenocarcinoma (PDAC) in the body and tail of the pancreas is associated to adjacent organ or vessel invasion. In only 15–20% of patients, surgical resection is possible at the time of diagnosis, being the only curative treatment for PDAC.¹ Based on two randomized trials, laparoscopic distal pancreatectomy (LDP) is widely accepted as a standard surgical procedure for left-sided pancreatic tumors.^2–5 However, the validity of the laparoscopic approach is still unclear for PDAC since the mobilization and holding of the pancreatic body during laparoscopic dissection (‘touch’ technique), may cause cancer cell dissemination through the blood stream via the portal vein (PV), theoretically increasing the risk of distant metastases. Strasberg et al. emphasized a meticulous surgical dissection with formal lymphadenectomy and the adoption of ‘no-touch’ techniques in order to obtain a radical oncological resection and minimizing the risk of tumor dissemination and seeding.⁶ A laparoscopic ‘no-touch’ technique might minimize the spread of cancer cells via the hematogenous metastatic route in patients with PDAC. However, studies comparing a ‘no-touch’ versus a ‘touch’ technique are exiguous. ⁷ Although there is no randomized study regarding LDP versus open distal pancreatectomy (ODP) in patients with PDAC, LDP is a well-accepted approach in selected patients. A recent comparative study found no significant differences between the laparoscopic and open approach groups for 3-year recurrence-free and overall survival rate.⁸ Recently, the international randomized DIPLOMA trial was completed which studies the non-inferiority of minimally invasive distal pancreatectomy versus ODP regarding the microscopically radical resection rate in patients with resectable PDAC.⁹

To date, data on laparoscopic technique standardization, particularly for PDAC, are scarce. Asbun et al. reported their clockwise approach for dissection, combined with the progressive stepwise compression technique for pancreatic transection, which resulted in a very low rate of postoperative pancreatic fistula (POPF) rate did not report on cancer recurrence as an outcome. ¹⁰ Furthermore, only few studies have reported on oncological results concerning a ‘en-bloc technique’ on laparoscopic distal pancreatectomy for both benign and malignant conditions.^11–13

The aim of this study is to evaluate the surgical results and the oncological outcomes between the ‘no-touch’ vs the ‘touch’ technique across two university hospitals.

Patients

From 2001 to 2020, we analyzed the data of 174 consecutive patients from two university hospitals (IMM and Amsterdam UMC) with PDAC in the pancreatic body or tail.

In IMM the two techniques have been adopted since 2001 as was in Amsterdam UMC during their entire inclusion period (2013–2020). Before 2013, LDP was not performed in Amsterdam UMC. Procedures were performed by 4 surgeons (IMM 3, Amsterdam UMC 1) We excluded 65 patients after ODP, 54 patients with other cancers (metastatic disease from renal cancer, sarcoma, etc…).

We analyzed 55 patients undergoing LDP for PDAC. A senior surgeon assisted by one or two senior trainees or fellows performed the procedures. All patients had pre-operatively evaluation using computed tomography (CT) of the abdomen and pelvis. In one center (IMM) magnetic resonance imaging (MRI) was performed routinely to exclude liver metastasis. Endoscopic ultrasound with biopsy was performed if needed. The clinical records of these patients were retrospectively reviewed.

Surgical procedure

Patients were positioned in decubitus with split legs and bent at the knees. Typically, four ports are inserted. For the camera a 10/12-mm port was placed near the umbilicus. In addition, three 5-mm trocars were placed at the left upper quadrant and subxyphoidal area. Left colon and splenic flexure was medially mobilized. Optionally, an additional 10/12 mm port was placed below the right costal margin if a ultrasound was required. The greater omentum was divided from left to right and the transverse mesocolon was separated from the Gerota fascia. The superior margin was then dissected including Gerota fascia. A soft grasper was placed on the Gerota fascia in order to continue the dissection without touching the pancreas (‘no-touch’ technique). This included the use of a vessel loop in Amsterdam UMC. ^7,14 Mobilization of the body and tail of the pancreas with Gerota fascia was performed “en bloc” while exposing laterally to medially, the surface of the left kidney and left renal vein. The pancreas was retracted superiorly and anteriorly, and the dissection behind the neck of the pancreas was continued from caudad to cephalad to expose the junction between the splenic vein and the superior mesenteric vein. The dissection of the inferior margin and the development of the posterior plane were continued clockwise¹⁵ towards the splenic/superior mesenteric vein junction. The inferior mesenteric vein was exposed too. The pancreas was then dissected from the hepatic artery and the coeliac trunk performing a full nodal clearance including lymph node station 8. Close to the stomach, the dissection was continued along the superior edge of the pancreas from medial to lateral, transecting the posterior gastric artery if any. The posterior branch of the splenic artery/vein was ligated and divided as the distal pancreas was approached, preserving the left gastroepiploic pedicle. The section of the tissues between the pancreas and the splenic hilum completed the “en bloc” LDP. The final step was to use a non-absorbable monofilament suture to over sewn the stump of the main pancreatic duct and the stump of the pancreas (IMM) or to staple the pancreas using a “graded compression” as technique as described by Asbun et al in Amsterdam UMC. In IMM, the spleen was preserved by ligation of the splenic vessels (the Warshaw technique) whereas the spleen was resected in Amsterdam UMC.¹⁶ The resected specimen was placed in a plastic bag and retrieved through a suprapubic small incision or an enlarged umbilical port. A drain was placed in the splenic cavity with the tip and the transection plane of the pancreas.

In summary, our ‘no-touch’ technique was based on two important steps. First, Gerota’s fascia was included, exposing the left kidney, left renal vein, and left adrenal vessels/gland to ensure a negative margin, this is the plane of the posterior radical antegrade modular pancreatosplenectomy without excision of the left adrenal gland.^17,18 Second, lymphadenectomy of the common hepatic artery and the celiac trunk was performed, as well as dissection of the superior mesenteric artery's neuroplexus on the left side.

Outcome measures

Morbidity was assessed with the Clavien-Dindo classification was used.¹⁹ The International Study Group of Pancreatic Surgery (ISGPS) definitions were used to classify pancreatic fistula and post-pancreatectomy hemorrhage (PPH).^20–21 Blood tumor marker measurements (carcinoembryonic antigen and carbohydrate antigen 19 − 9), contrast-enhanced CT, and/or MRI were performed every 3 months after discharge as part of the follow-up evaluation or on indication. The overall survival (OS) was considered as interval between the surgery and last follow-up (death or alive) while the disease-free survival (DFS) was calculated as interval between the surgery and death or recurrence (first event). The Time to recurrence (TTR) was the time from date of curative surgery to the time of recurrence. ^22,23 A margin width > 1mm was classified as R0 resection, while a margin width ≤ 1mm was classified as R1 resection.

Statistical Analysis

All quantitative data are expressed as median (interquartile range: IQR). Qualitative data are expressed as percentages. The Kruskal-Wallis test for continuous variables and Pearson’s chi-square test were used when applicable, or Fisher’s exact test for categorical variables. Survival rates were calculated using the Kaplan–Meier method, and groups were compared with the log-rank test. Pathological and perioperative variables were assessed as predictors of outcomes using Cox proportional hazards models. Factors significantly associated with TTR were identified using univariable and multivariable Cox analyses. Statistical analyses were performed using SPSS 20.0 (SPSS Inc, Chicago, IL, United States). A p-value ≤ 0.05 was considered to be statistically significant.

Ethics

Patient’s records were anonymized prior to analysis. No additional ethical review was required.

Patient demographics

Overall, 55 patients after LDP for PDAC were included. Clinico-demographic characteristics of the ‘no-touch’ and ‘touch’ groups were not statistically different as shown in Table 1.

Table 1

Patient demographics
	No-touch n = 41	Touch n = 14	p
Sex			0.82
Male	22 (53.7)	8 (57.1)
Female	19 (46.3)	6 (42.9)
Age	67.2 [59.5–74.5]	66.2 [54.2–77.5]	0.75
Asa score			0.45
I	11 (26.8)	4 (28.6)
II	24 (58.5)	6 (42.9)
III	6 (14.6)	4 (28.6)
BMI	25.5 [22.7–28.6]	23.4 [21.9–24.7]	0.36
Localization			0.18
Body	20 (48.7)	11 (78.6)
Tail	21 (51.3)	3 (21.4)
CA19.9 (median)	125 [49–607]	48 [31–84]	0.39
CEA (median)	2.9 [1.6–5.5]	0.8 [0.5–2.5]	0.01
Neoadjuvant chemotherapy	6 (15)	2 (15.4)	0.97
Neoadjuvant Radiotherapy	2 (4.9)	0	0.40
n = number [ ] = IQR; ( ) = percentage; CEA = carcinoembryonic antigen; Asa = American Society of Anesthesiologists.

Intra- and postoperative outcome

Intraoperative factors and postoperative complications are summarized in Table 2.

Table 2

Intra- and postoperative outcome
	No-touch n = 41	Touch n = 14	p
Operative time (median, min)	245 [196–300]	270 [240–330]	0.30
EBL (median, ml)	200[100–400]	150 [50–725]	0.86
Conversion	4 (9.8)	5 (35.7)	0.02
Splenectomy	22 (53.7)	4 (29)	0.14
Splenic Vessel resection	32 (78)	12 (86)	0.54
Post operative complication CD I-IV	24 (58.5)	9 (64.3)	0.70
CD ≥ III	11 (26.8)	4 (28.6)	0.89
Length of hospital stay	11 [7–18]	18 [9–42.5]	0.13
Postoperative pancreatic fistula	10 (24.4)	4 (28.6)	0.75
Grade B	5 (15.6)	2 (14.3)
Grade C	0	1 (7.1)
Post-pancreatectomy hemorrhage			0.42
Grade B	3 (7.3)	1 (7.1)
Grade C	1 (3.1)	1 (7.1)
n = number [ ] = IQR; ( ) = percentage; CD = Clavien-Dindo ; EBL = Estimated blood loss

There were no difference concerning operative time, estimated blood loss across the two group. Patients that underwent splenectomy were 22 (53.7%) for ‘no touch’ group and 5 (35.7%) for ‘touch’ group p = 0.05).

The conversion rate was lower in the ‘no-touch’ group 4 (9.8%) vs 5 (35.7%); p = 0.02. The rate of postoperative complications, including POPF and PPH did not differ between the two groups.

Histopathology

Histological examination with all details are shown in Table 3. The rate of R1 resection was for ‘no touch’ group 7 (17%) and for ‘touch’ group was 3 (21); p = 0.70.

The median tumor size was 34.5 mm [28.5–44.5] and 24.5[18.7–31.2] for ‘no-touch’ and ‘touch’group, respectively. The median number of lymph nodes resected in all patients was 17, 17 [13–25] for ‘no-touch’ vs 16 [13–21] (p = 0.73) and number of positive lymph node was not different across the two group (p = 0.93). Tumor differentiation and TNM stage were not different for the two groups.

Table 3

Histopathology
	No-touch n = 41	Touch n = 14	p
Tumor size (median, mm)	34.5 [28.5–44.5]	24.5[18.7–31.2]	0.03
Perineural invasion	30 (75)	10 (83)	0.54
Lymphovascular emboli	15 (47)	5 (46)	0.93
Harvested lymph nodes	17 [13–25]	16 [13–21]	0.73
Positive lymph nodes	1 [0–3]	1 [0-3.2]	0.93
R1 rate	7 (17)	3 (21)	0.70
T stage			0.09
1	2 (5.3)	4 (31)	0.80
2	13 (34.2)	3 (23)
3	21 (55.3)	6 (46.2)
4	2 (5.3)	0
N stage			0.80
0	16 (39)	6 (43)
1	22 (53)	7 (50)
x	3 (8)	1 (7)
n = number [ ] = range; ( ) = percentage;

Oncological outcome

The access to adjuvant chemotherapy and adjuvant radiotherapy did not differ between the groups as shown in Table 4. Recurrence (distant and local recurrence) occurred in 18 patients (43.8%) in the ‘no-touch’ group and in 12 patients (85.7%) in the ‘touch’ group (p = 0.01). The location of recurrence significantly differed between the two groups (p = 0.03).

Table 4

Oncological outcome. Table 4. Univariate and Multivariate Analysis for TTR
		Touch n = 14	p
Adjuvant chemotherapy	24 (58)	8 (57)	1
Adjuvant radiotherapy	12 (29)	1 (7)	0.14
Recurrence	18 (43.8)	12 (85.7)	0.007
Site of recurrence			0.01
Local	5 (15.6)	4 (30.8)
Distant	11 (26.8)	8 (57)
Type of recurrence			0.03
Carcinosis	3 (7.3)	3 (21.4)
Liver	8 (19)	3 (21)
Pulmonary	0 (0)	2 (14)
n = number; ( ) = percentage.

The OS rates in the ‘no-touch’ and ‘touch’ groups were 95% vs 78% (1-year OS); 50% vs 50% (3-year OS), respectively (p = 0.60). The DFS rates in the ‘no-touch’ and ‘touch’ groups were 72% vs 57% (1-year DFS); 32% vs 28% (3-year DFS), respectively (p = 0.11). The TTR rates in the ‘no-touch’ and ‘touch’ groups were 77% vs 61% (1-years TTR); 54% vs 30% (3-year TTR); 46% vs 11% (5-year TTR), respectively (p = 0.02), as shown in Fig. 1.

In univariate analysis, significant predictors of TTR were Touch technique (OR 2.36; p = 0.02), lymphovascular emboli (OR = 4.38; p = 0.003). In multivariate analysis the only factors were Touch technique (OR = 2.62, p = 0.02) and lymphovascular emboli (OR = 4.8; p = 0.002), as shown in Table 5.

Table 5

Univariate and Multivariate Analysis for TTR
					Multivariate Analysis
	OR	CI	p value	OR	CI	p value
Age < 65/ ≥ 65	0.81	0.39–1.70	0.59
Sex, M/F	1.07	0.57–2.013	0.81
ASA I II/III	0.93	0.35–2.44	0.88
EBL < 200/≥ 200*	0.13	0.84–3.64	0.13
T 1–2/3	1.8	0.85–3.86	0.12
Lymph nodes harvested ≤ 17/ >17 *	1.34	0.64–2.79	0.43
Positive Lymph nodes yes/no	1.2	0.58–2.63	0.57
Splenic vessels resection	1.03	0.41–2.34	0.94
Splenectomy	1.19	0.55–2.55	0.65
Perineural invasion	2.1	0.74–6.3	0.15
Lymphovascular emboli	4.38	1.65–11.63	0.003	4.8	1.79–12.89	0.002
R1 yes/no	0.68	0.23–1.97	0.48
Adjuvant Chemotherapy	0.96	0.54–1.70	0.90
Touch	2.36	1.12–4.99	0.02	2.62	1.16–5.88	0.02
• The cut-off values for EBL and lymph node harvested was set on the mean value of the whole study population.

This first retrospective bi-center study to describe the results of ‘no-touch’ vs ‘touch’ laparoscopic left pancreatosplenectomy in patients with PDAC found the ‘no-touch’ technique to be associated with improved oncological outcome. These associations included improved 1-year TTR 77% vs 61% (p = 0.02); 3-year TTR 54% vs 30% (p = 0.02) and 5-year TTR 46% vs 11% (p = 0.02); recurrence rate (43.8% vs 85.7% p = 0.007), distant recurrence rate (26.8% vs. 57%, p = 0.01) and also for the type of recurrence. These results show that in our series ‘touch groups’ tend to recurrence more frequently and even earlier.

The type of recurrence and the median time to recurrence and patterns of disease recurrence after resection of pancreatic cancer is theme of great debate. Jones RP et al. showed in their study in a multivariate analysis that positive resection margin and local invasion were significantly associated with poor survival and that local recurrence also trended to being significantly associated with worse survival (p = 0.054).²⁴ In other words, the recurrence can indirectly affect the survival. In our study, we differentiate the type of survival and we believe that TTR rather than DFS may be the optimal study endpoint for predicting early recurrence. By the way, OS and DFS was superior in No touch group but the p value was not significant.

There have been studies that have talked about the ‘no touch’ technique about the resection of pancreatic adenocarcinoma. ^7,14,25,26 All of them advocate this technique based on the theoretical principle that less carcinoma dissemination occurs and that Gerota's fascia may function as a barrier against protease-mediated invasion of cancer cells.

About the survival analysis only Hiorota et al. showed in their 16 patients series that the 1- and 5-year OS survival rates were 86 and 71% and at 1- and 5-year DFS rates were 72 and 57%, 7 were positive for anterior serosal invasion. ²⁵ This is at our knowledge the only comparative study with a standardized mini invasive technique.

The result of our OS is in line with other study. ^27–29 Oncological surgery necessitates a radical resection, adequate lymphadenectomy, and meticulous “no-touch” dissection to avoid seeding and tumor cell dissemination. ^25,26 Strasberg et al. proposed radical antegrade modular pancreatosplenectomy (RAMPS) as a surgical procedure for pancreatic cancer in the body and tail of the pancreas. In this technique the dissection begins from the medial to the lateral side, following the early division of the neck of the pancreas and the early ligation of the splenic vessels. Traditional distal pancreatosplenectomy, on the other hand, is performed from left to right, with mobilization of the pancreatic tail and spleen.³⁰ RAMPS can, therefore, be considered as a surgical procedure that uses a no-touch isolation technique. ²⁶ Mitchem et al. compared anterior vs posterior RAMPS and they affirmed that RAMPS is associated with high negative tangential margin rates and very satisfactory survival rates for this aggressive tumor.¹⁷

The conversion rate was lower in the ‘no-touch’ group. Several studies have identified and evaluated preoperative predictors of conversion, such as patients with vascular proximity (< 1 cm) of the tumor on preoperative imaging, undergoing a subtotal pancreatectomy, tumor located in the body of the pancreas, preoperative findings of malignancy, resection extending to the neighboring organs, and surgeon expertise, which would aid in the proper selection of an operative approach. ^31–35 The higher rate in the touch group of current study can be explained to the suboptimal exposure of the Gerota fascia and that manipulation of the pancreas can cause bleeding from peripancreatic vessels, in other words behind the Gerota's fascia, there is no way to dissect retropancreatic vasculature that could bleed and force the surgeon to convert urgently.

The concepts of the ‘no-touch’ technique from current study is comparable with removal of the Gerota fascia. A hanging and clamping maneuver of the peripancreatic retroperitoneal tissues not only allows proper clearance of tissue along the SMA, celiac artery, and abdominal aorta, but also allows for easier dissection of the plane posterior to the Gerota fascia. Resecting cancer wrapped within the Gerota fascia may act as a barrier against protease-mediated cancer invasion. Strasberg et al., chose two dissection planes based on the extent of the cancers' retroperitoneal invasion. ^25,30,36 They dissected along the anterior surface of the adrenal gland if the cancer did not invade the gland, and along the posterior plane of the adrenal gland if the cancer invaded the gland or penetrated deeper. Their technique is similar to ours, but they only remove the medial part of Gerota fascia, on the contrary we try to use the whole Gerota fascia to mobilize the pancreatic block, laparoscopically. Their method, however, is not associated with the no-touch method, which is the main feature of our technique. By clamping and tractioning to the left the Gerota fascia we can ameliorate the exposition of the retroperitoneal tissue improving the clearance of the nervous and lymphatic tissue along the SMA and celiac artery. ⁷ A large international study also found an association between resecting Gerota’s fascia and improved survival. ³⁷ The difference between ‘no-touch’ and ‘touch’ could also be explained by a difference of including Gerota in the dissection specimen. However, one would then probably expect a higher R1 resection rate in the ‘touch’ group which was not confirmed by the present study. The rate of R1 resection was not statistically different across the two group (‘no touch’ group 17% and for ‘touch’ group was 21%; p = 0.70.).

The rate of patients that underwent splenectomy was not significantly different; 53.7% of the patients in the ‘no touch’ group vs 29% of the patients in ‘touch’ group underwent splenectomy.

A consensus conference of the International Study Group on Pancreatic Surgery (ISGPS) established that standard lymphadenectomy during DP should include stations 10 (nodes at the splenic hilum), 11 (nodes along the splenic artery), and 18 (nodes along the inferior border of the pancreatic body-tail)³⁸. However, the frequency of tumor involvement and the specific prognostic impact of these LN stations remain unknown.

Based on the low rate of station 10 involvement reported in Eastern and Western series, some authors suggested that splenectomy could be avoided in patients with body tumors and no suspected splenic or splenic hilum involvement in preoperative imaging.^39,40 In particular Collard et al suggest that routine splenectomy is not mandatory during distal pancreatectomy for PDAC, since fewer patients have splenic hilum station 10 LNs than previously expected and preoperative CT is accurate to diagnose tumoral involvement of the spleen or splenic hilum by contiguity.

On the contrary another Italian study advocate the performance of routine splenectomy to ensure an adequate lymphonodes staging and tumor clearance because lymphnodes at the splenic hilum resulted to be an independent prognostic factor on multivariable analysis.⁴¹

Our goal is not to evaluate the oncological efficacy of splenectomy because our series is very small and other multicenter studies will have to be done to stratify the need for splenectomy. In our opinion, oncological radical resection must also be achieved in removing the lymph nodes in the posterior part of the pancreas. In our series, the number of lymph nodes harvested is not different between the two groups, but this could be explained by the fact that during the study, we did not have standardization of the evaluation of the lymph nodes.

In addition, concerning short term outcome distal pancreatectomy with splenectomy can worsen the short-term prognosis in terms of postoperative comorbidity⁴²

In multivariate analysis of risks factors the Touch technique (OR = 2.41, p = 0.05) and lymphovascular emboli (OR = 5.39; p = 0.02) are identified as independent factor influencing DFS, and in our series lymphovascular emboli did not differ across the two group. Splenectomy and splenic vessel resection did not shown to affect the DFS. These findings support the notion that the ‘no-touch’ technique should be adopted if possible.

Concerning post-operative complications and POPF we did not find any significant difference across the two groups By the way the only case of POPF grade C was in the touch group. At the moment there is no consensus on the pancreatic transection during distal pancreatectomy to reduce postoperative pancreatic fistula (POPF), but meta-analysis showed that a reinforced stapling in DP is safe and seems to reduce POPF grade B/C with similar mortality rates, postoperative bleeding, and reoperation rate.⁴³

We do not have any patients treated with this stapler in this study.

The results of the current study should be interpreted in light of several limitations. First, and most importantly, selection bias is present because of the study's retrospective character which might have led that a technique was chosen by favorable patients or disease characteristics. Although the effect of this bias was will be minimal since the demographics and preoperative details did not differ between the techniques, no causal relationship can be established based on a retrospective study. Nevertheless, since there seem to be no obvious downsides to the ‘no-touch’ approach in terms of morbidity or operating time we advise to use this approach. Second, bias may have been introduced due to the change in technique in IMM. Hereby, more surgical experience could have been present in the second period. This is also suggested by the higher conversion rate in the ‘touch’ group. However, this would still emphasize our advice that adequate surgical technique influences oncological outcomes, including survival. Third, the number of included patients is low and therefore the statistical power was decreased. Since the laparoscopic approach specifically on PDAC was our topic of interest, unfortunately, a considerable amount of patients were excluded. Fourth, heterogeneity was introduced since data from two different centers were include. Also several surgeons performed the operation and therefore this could have led to different outcomes because of surgeon-specific characteristics.

The main strength of this study is the comparison between two surgical approaches for LDP in patients with pancreatic cancer in two experienced high-volume centers.

Despite the lack of randomized studies, we advise a ‘no-touch’ technique in patients with resectable PDAC in the pancreatic body and tail based on this retrospective bi-center study. Although this study does not provide definitive proof of superiority, no apparent downsides are present for the ‘no-touch’ technique in this setting although there could be oncological benefits. Ultimately, only randomized trials will have to confirm the superiority of a ‘no-touch’ technique but one can argue whether there truly is a ‘equipose’ which would require theoretical benefits of a ‘touch’ technique’ which were not objectified by this study.

Amsterdam UMC = Amsterdam University Medical Centers

DFS = Disease Free Survival

IMM = Institut Mutualiste Montsouris

LDP = Laparoscopic distal pancreatectomy

N = lymph nodes

OS = Overall Survival

ODP = open distal pancreatectomy

PDAC = pancreatic ductal adenocarcinoma

POPF = Postoperative pancreatic fistula

PPH = postpancreatectomy hemorrhage

TTR = time to recurrence

SMA = superior mesenteric artery

Acknowledgements

Not applicable.

Authors' contributions

AM, EVB and SU: drafted the manuscript

AM, EVB and AC edited the manuscript

AM statistical analysis

ET, SB, JMF, BG, ORB, OS and MGB: co-authored the writing of the manuscript

OS and MGB: scientific supervision, methodology, global work supervision, reviews manuscript

All authors read and approved the final manuscript

Funding

No funding was obtained for this study.

Availability of data and materials

The datasets used and/or analysed during the current study are available from

the corresponding author on reasonable request.

Ethics approval and consent to participate

All methods of our study were carried out in accordance with relevant guidelines and regulations. Data collection and analysis followed the ethical guidelines of the World Medical Association Declaration of Helsinki. The study was approved by the Human Ethics Committee of Amsterdam UMC, University of Amsterdam and the Human Ethics Committee of Institut Mutualiste Montsouris, Paris. The CEPAR and the Clinical Research Unit of the IMM (Comité d’Éthique IMM) has review the article and approved this article research with a number of reference (CEPAR: 2022-10).

Written informed consent was obtained from the patients and/or their legal guardians.

Consent for publication

Competing interests

The authors declare that they have no competing interests.

Disclosure: The authors of this manuscript have no conflicts of interest to disclose.

Maloney S, et al. Optimal Upfront Treatment in Surgically Resectable Pancreatic Cancer Candidates: A High-Volume Center Retrospective Analysis. J Clin Med. 2021;10:2700.
De Rooij T, et al. Minimally Invasive Versus Open Distal Pancreatectomy (LEOPARD): A Multicenter Patient-blinded Randomized Controlled Trial. Ann Surg. 2019;269:2–9.
Björnsson B, Larsson AL, Hjalmarsson C, Gasslander T, Sandström P. Comparison of the duration of hospital stay after laparoscopic or open distal pancreatectomy: randomized controlled trial. Br J Surg. 2020;107:1281–8.
Nakamura M, Nakashima H. Laparoscopic distal pancreatectomy and pancreatoduodenectomy: is it worthwhile? A meta-analysis of laparoscopic pancreatectomy. J Hepatobiliary Pancreat Sci. 2013;20:421–8.
Mehrabi A, et al. A systematic review and meta-analysis of laparoscopic versus open distal pancreatectomy for benign and malignant lesions of the pancreas: It’s time to randomize. Surgery. 2015;157:45–55.
Strasberg SM, Drebin JA, Linehan D. Radical antegrade modular pancreatosplenectomy. Surgery. 2003;133:521–7.
Abu Hilal M, et al. Laparoscopic radical ‘no-touch’ left pancreatosplenectomy for pancreatic ductal adenocarcinoma: technique and results. Surg Endosc. 2016;30:3830–8.
Chen K, et al. Laparoscopic versus open distal pancreatectomy for pancreatic ductal adenocarcinoma: a single-center propensity score matching study. Updates Surg. 2020;72:387–97.
van Hilst J, et al. Minimally invasive versus open distal pancreatectomy for pancreatic ductal adenocarcinoma (DIPLOMA): study protocol for a randomized controlled trial. Trials 22, (2021).
Asbun HJ, et al. Technique and audited outcomes of laparoscopic distal pancreatectomy combining the clockwise approach, progressive stepwise compression technique, and staple line reinforcement. Surg Endosc. 2020;34:231–9.
Kawaguchi Y, Fuks D, Nomi T, Levard H, Gayet B. Laparoscopic distal pancreatectomy employing radical en bloc procedure for adenocarcinoma: Technical details and outcomes. Surgery. 2015;157:1106–12.
Lee SH, et al. Minimally invasive RAMPS in well-selected left-sided pancreatic cancer within Yonsei criteria: long-term (> median 3 years) oncologic outcomes. Surg Endosc. 2014;28:2848–55.
Kim HS, Hong TH, You YK, Park JS, Yoon DS. Radical antegrade modular pancreatosplenectomy (RAMPS) versus conventional distal pancreatectomy for left-sided pancreatic cancer: findings of a multicenter, retrospective, propensity score matching study. Surg Today. 2021;51:1775–86.
Vissers FL, et al. Laparoscopic Radical Left Pancreatectomy for Pancreatic Cancer: Surgical Strategy and Technique Video. J. Vis. Exp. 2020, 1–6 (2020).
Asbun HJ, Stauffer JA. Laparoscopic approach to distal and subtotal pancreatectomy: a clockwise technique. Surg Endosc. 2011;25:2643–9.
Warshaw AL. Conservation of the Spleen With Distal Pancreatectomy. Arch Surg. 1988;123:550–3.
Mitchem JB, et al. Long-Term Results of Resection of Adenocarcinoma of the Body and Tail of the Pancreas Using Radical Antegrade Modular Pancreatosplenectomy Procedure. J Am Coll Surg. 2012;214:46–52.
Shimada K, Sakamoto Y, Sano T, Kosuge T. Prognostic factors after distal pancreatectomy with extended lymphadenectomy for invasive pancreatic adenocarcinoma of the body and tail. Surgery. 2006;139:288–95.
Clavien PA, et al. The Clavien-Dindo classification of surgical complications: five-year experience. Ann Surg. 2009;250:187–96.
Bassi C, et al. Postoperative pancreatic fistula: An international study group (ISGPF) definition. Surgery. 2005;138:8–13.
Wente MN, et al. Postpancreatectomy hemorrhage (PPH)–An International Study Group of Pancreatic Surgery (ISGPS) definition. Surgery. 2007;142:20–5.
McLean KA, et al. Death following pulmonary complications of surgery before and during the SARS-CoV-2 pandemic. Br J Surg. 2021;108:1448–64.
Liu Y, Yang T, Wei YW. What is the difference between overall survival, recurrence-free survival and time-to-recurrence? Br J Surg. 2020;107:e634–4.
Jones RP, et al. Patterns of Recurrence After Resection of Pancreatic Ductal Adenocarcinoma: A Secondary Analysis of the ESPAC-4 Randomized Adjuvant Chemotherapy Trial. JAMA Surg. 2019;154:1038–48.
Hirota M, et al. Distal pancreatectomy using a no-touch isolation technique. Scand J Surg. 2012;101:156–9.
Kuroki T, Eguchi S. No-touch isolation techniques for pancreatic cancer. Surg Today. 2017;47:8–13.
Kwon J, et al. Clinical Outcome of RAMPS for Left-Sided Pancreatic Ductal Adenocarcinoma: A Comparison of Anterior RAMPS versus Posterior RAMPS for Patients without Periadrenal Infiltration. Biomedicines 9, (2021).
Kooby DA, et al. A Multicenter Analysis of Distal Pancreatectomy for Adenocarcinoma: Is Laparoscopic Resection Appropriate? J Am Coll Surg. 2010;210:779–85.
Zhang H, et al. Comparison of minimal invasive versus open radical antegrade modular pancreatosplenectomy (RAMPS) for pancreatic ductal adenocarcinoma: a single center retrospective study. Surg Endosc. 2021;35:3763–73.
Strasberg SM, Drebin JA, Linehan D. Radical antegrade modular pancreatosplenectomy. Surgery. 2003;133:521–7.
Lof S, et al. Outcomes of Elective and Emergency Conversion in Minimally Invasive Distal Pancreatectomy for Pancreatic Ductal Adenocarcinoma: An International Multicenter Propensity Score-matched Study. Ann Surg. 2021;274:E1001–7.
Casadei R, et al. Laparoscopic versus open distal pancreatectomy in pancreatic tumours: A case-control study. Updates Surg. 2010;62:171–4.
Casadei R, et al. Laparoscopic distal pancreatectomy: which factors are related to open conversion? Lessons learned from 68 consecutive procedures in a high-volume pancreatic center. Surg Endosc. 2018;32:3839–45.
Partelli S, et al. Preoperative predictive factors of laparoscopic distal pancreatectomy difficulty. HPB. 2020;22:1766–74.
Goh BKP, et al. Factors associated with and consequences of open conversion after laparoscopic distal pancreatectomy: initial experience at a single institution. ANZ J Surg. 2017;87:E271–5.
Strasberg SM, Linehan DC, Hawkins WG. Radical Antegrade Modular Pancreatosplenectomy Procedure for Adenocarcinoma of the Body and Tail of the Pancreas: Ability to Obtain Negative Tangential Margins. J Am Coll Surg. 2007;204:244–9.
Korrel M, et al. Predictors for Survival in an International Cohort of Patients Undergoing Distal Pancreatectomy for Pancreatic Ductal Adenocarcinoma. Ann Surg Oncol. 2021;28:1079–87.
Tol JAMG, et al. Definition of a standard lymphadenectomy in surgery for pancreatic ductal adenocarcinoma: a consensus statement by the International Study Group on Pancreatic Surgery (ISGPS). Surgery. 2014;156:591–600.
Kim SH, et al. Proposal for splenectomy-omitting radical distal pancreatectomy in well-selected left-sided pancreatic cancer: multicenter survey study. J Hepatobiliary Pancreat Sci. 2013;20:375–81.
Collard M, et al. Is Routine Splenectomy Justified for All Left-Sided Pancreatic Cancers? Histological Reappraisal of Splenic Hilar Lymphadenectomy. Ann Surg Oncol. 2019;26:1071–8.
Malleo G, et al. Reappraisal of nodal staging and study of lymph node station involvement in distal pancreatectomy for body-tail pancreatic ductal adenocarcinoma. Eur J Surg Oncol. 2020;46:1734–41.
He Z, et al. Clinical comparison of distal pancreatectomy with or without splenectomy: a meta-analysis. PLoS One 9, (2014).
Oweira H, et al. Using a Reinforced Stapler Decreases the Incidence of Postoperative Pancreatic Fistula After Distal Pancreatectomy: A Systematic Review and Meta-Analysis. World J Surg. 2022;46:1969–79.

No competing interests reported.

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Oncological outcome after laparoscopic ‘no-touch’ versus ‘touch’ left pancreatectomy for pancreatic adenocarcinoma

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Surgical procedure

Outcome measures

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Intra- and postoperative outcome

Histopathology

Oncological outcome

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