“Laparoscopic Para-Aortic Lymph Node Sampling” First Approach for Pancreatic Adenocarcinoma as an Oncological Practice

Abstract

Background:

In the setting of pancreatic ductal adenocarcinoma (PDAC), para-aortic lymph node (PALN) involvement is considered as a metastasis disease. To date, no morphological examination can effectively identify lymph node metastasis, and a significant number of patients undergo futile invasive laparotomy for PALN involvement. From an oncological point of view, laparoscopy represents a better approach for PALN sampling. The main aim of the study is to propose a laparoscopic PALN sampling first approach. We describe the surgical technique and demonstrate its technical feasibility as a routine approach as the first surgical step before pancreaticoduodenectomy for localized PDAC.

Materials and Methods:

During a first step of staging laparoscopy, PALN sampling was done for 31 patients with localized PDAC between November 2015 and February 2017. Demographic data and intraoperative, postoperative, and pathological criteria were evaluated. The surgical technique is described in detail.

Results:

The median operative time was 35 (range 18–65) minutes. The median number of PALN analyzed per patient was 2 (range 1–5). Four (13%) of 31 patients had positive PALN in frozen section analysis. No severe complication was reported for patients with positive PALN, receiving laparoscopic exploration and PALN sampling. The median hospital stay for patients with positive PALN was 2 (range 1–7) days.

Conclusion:

To avoid futile laparotomy, a staging laparoscopy is usually carried out. We report the feasibility and safety of laparoscopic PALN sampling and suggest its systematic realization during staging laparoscopy as a first step in patients with localized PDAC before pancreaticoduodenectomy.

Introduction

The prognosis of patients with localized (resectable or borderline) pancreatic ductal adenocarcinoma (PDAC) remains poor. Surgical resection remains the only curative treatment for patients with PDAC. However, even if patients undergo complete surgical resection with completion of adjuvant chemotherapy, the overall 5-year survival rate is around 25% with high rates of early recurrence.^1–3 This dismal prognosis is, in part, related to the high frequency of distant lymph node (LN) metastasis, undiagnosed preoperatively. LN metastasis of PDAC primarily involves peripancreatic nodes and eventually spreads to distant LNs, including the para-aortic LNs (PALN group 16b of the Japanese Classification).^4–8

We recently reported that metastasis to PALNs implies systemic metastasis, and resection is therefore not recommended.⁵

Although cross-sectional imaging has improved considerably during the last decade, providing fairly reliable predictors of vascular invasion in pancreatic cancer, the preoperative diagnosis of LN involvement in pancreatic cancer, is still hazardous.⁹ LN size remains the most frequently used criterion, although not accurate on morphologic imaging.^10–12

PALN dissection during radical pancreatectomy for PDAC should be systematically performed.⁵ For most centers, staging laparoscopy is considered as the first step of the surgical procedure before pancreatic resection. However, the feasibility, safety, and efficacy of laparoscopic PALN sampling and its oncologic impact have never been reported in the setting of PDAC.

From an oncological point of view, a minimally invasive laparoscopic approach should be the preferred option for peritoneal staging and PALN sampling, as the first step of pancreaticoduodenectomy with regard to quality of life and time to induction of chemotherapy especially in situations of palliative care.

To address this issue, we aimed to describe the surgical technique and demonstrate that laparoscopic PALN sampling is technically feasible, not time consuming, and could have an oncological impact on the management of nonresectable/metastatic PDAC.

Materials and Methods

Study patients

Laparoscopic PALN sampling during staging laparoscopy was attempted in 31 patients with resectable or borderline PDAC between November 2015 and February 2017.

Resectable or borderline anatomic staging of PDAC was defined using the NCCN classification.¹³

Preoperative patient assessment was carried out using multidetector contrast-enhanced computed tomography, magnetic resonance imaging, endoscopic ultrasonography, and/or positron emission tomography (PET), following European Society for Medical Oncology (ESMO) guidelines.¹⁴

Upfront surgery and neoadjuvant chemotherapy, with or without chemoradiation, followed by surgery were used for patients with resectable and borderline PDAC, respectively, according to ESMO guidelines.

The Institutional Review Board of Rouen University hospital approved this study (Study number E2018-78).

Surgical technique and steps

Position

The patient was placed in supine split-leg position, with the surgeon between the patient's legs. The first assistant stood on the right of the patient and the second assistant on the left side. The operating room nurse was positioned just behind the patient to the left. The surgical team had access to two screens placed on either side of the patient's head.

Placement of the trocars

The pneumoperitoneum was insufflated through a 12 mm midline trocar placed 2 cm above the umbilicus with the open entry technique, and pneumoperitoneum pressure was maintained between 12 and 14 mmHg. The camera was introduced through the trocar, and the abdominal cavity was explored. After careful inspection of the abdominal cavity, by visual control, two operating trocars of 12 mm were placed on the right and left midclavicular line ∼1 to 2 cm cranial to the camera trocar. Then a 5 mm epigastric trocar was placed 1 to 2 cm under the xiphoid process. An additional 5 mm trocar for retraction was placed on the left anterior axillary line at the level of the umbilicus. Other trocars were placed if necessary.

Liver exploration, including posterior liver surface

The liver was raised up allowing examination of its posterior surface. Routine liver ultrasound is recommended at this step.

Proximal jejunal mesentery and lesser sac exploration

The transverse colon was retracted to examine the proximal jejunal mesentery. In the absence of metastases, by dividing the gastrocolic ligament using an ultrasonic dissector entered the lesser sac. In the absence of metastases, the duodenum was mobilized to examine the paraduodenal retroperitoneum.

Kocher maneuver

The first assistant retracted the liver with a fenestrated clamp introduced by the 5 mm epigastric trocar (Supplementary Videos 1 and 2). The right colonic angle was freed from its retroperitoneal attachments with an ultrasonic dissector. The right prerenal fascia was visible on the left of the screen and the duodenum on the right. The first assistant retracted the duodenum to the right and the second assistant pulled the transverse colon down; the posterior attachments of the duodenum were then gently freed with the ultrasonic dissector. A Kocher maneuver was performed, freeing the anterior surfaces of the inferior vena cava, aorta, and left renal vein, until incising the Treitz's ligament.

PALN sampling/lymphadenectomy of the aortocaval tissue

The second assistant retracted the second duodenal portion to the left (Supplementary Videos 3 and 4). The nodal dissection was started with the ultrasonic dissector by harvesting a 5 cm portion of the lymphocellular aortocaval tissue located below the left renal vein (group 16b of the Japanese Classification).⁴ We paid special attention to lymphostasis. The PALN sample was removed from the abdomen using a plastic surgical bag. Frozen section (FS) analysis was performed.

Results

Main results are shown in Table 1.

Table 1.

Characteristics of Patients, Tumors, and Therapy, N = 31

Patient characteristics ^a	PALN+(n = 4)	PALN–(n = 27)	Total (n = 31)
Age (years), median (range)	58 (41–68)	64 (50–78)	62 (41–78)
Gender, n (%)
Male	3	17	20 (64)
Female	1	10	11 (36)
BMI, kg/m², (mean ± SD)	25 ± 7.2	23 ± 4.5	23 ± 5.6
Tumor characteristics
Resectability, stage of PDAC^b, n (%)
PR	3	14	17 (54)
BR	1	13	14 (46)
Tumor size (mm), (mean ± SD)	24 ± 7	26 ± 11	26 ± 12
Tumor location
Head/neck	4	19	23
Uncus	0	8	8
Preoperative CA 19-9 (UI/mL), median (range)	152 (45–740)	208 (12–1030)	190 (12–1030)
Treatment characteristics
Neoadjuvant therapy, n (%)	2	12	14 (46)
FOLFIRINOX-based induction chemotherapy	1	8	9 (29)
FOLFIRINOX with chemoradiation	1	4	5 (16)
PALN sampling
Duration of laparoscopic staging with PALN sampling (minutes), median (range)	40 (25–60)	32 (18–65)	35 (18–65)
Conversion rate	0	0	0
No. of PALN analyzed/patient, median (range)	2 (1–4)	2 (1–5)	2 (1–5)
No. of patients with positive PALN (FS), n (%)	4	0	4 (13)
No. of patients with positive PALN (PE), n (%)	4	0	4 (13)

Baseline.

Before surgery, based on vascular anatomy according to NCCN classification.

BMI, body mass index; BR, borderline resectable; FS, frozen section; PALN, para-aortic lymph node; PDAC, pancreatic ductal adenocarcinoma; PE, paraffin-embedded sample analysis; PR, potentially resectable.

The median operative time was 35 (range 18–65) minutes.

The median numbers of PALN analyzed per patient was 2 (range 1–5). Four (13%) of 31 patients had positive PALN in FS analysis, and these results were confirmed by final pathological analysis. With regard to PALN positivity, no difference was observed between potentially resectable and borderline resectable PDAC.

Surgical outcomes for patients with positive PALN, receiving laparoscopic exploration and PALN sampling, are shown in Table 2. No severe complication was reported. We reported 9% of lymphatic complications (n = 3) in all 31 patients. In total, among these 3 patients, only 1 had only surgical exploration with LN dissection. Two patients developed a total of 3 postoperative complications. The median hospital stay for patients with positive PALN was 2 (range 1–7) days. The median delay to chemotherapy for patients with positive PALN was 10 (range 7–21) days.

Table 2.

Surgical Outcomes for Patients with Positive Para-Aortic Lymph Nodes, Receiving Laparoscopic Exploration and Para-Aortic Lymph Nodes, Only

Surgical outcomes for PALN+group	Patient 1	Patient 2	Patient 3	Patient 4
Initial hospitalization
Postoperative complication	None	DGE ISGPS grade ANo collection on CT scan	None	None
Duration of stay (days)	1	7	2	2
Readmission	No	No	Yes	No
Reason for readmission			DGE ISGPS grade APersistent inflammatory biological syndromeIntra-abdominal fluid collection on CT scan
Duration of stay (days)	—	—	3	—
Delay to chemotherapy (days)	7	12	21	10

n = 4.

CT, computed tomography; DGE, delayed gastric emptying; ISGPS International study group of pancreatic surgery; PALN, para-aortic lymph node.

Discussion

We describe herein the surgical technique of laparoscopic PALN sampling and report its feasibility, safety, and efficacy. Indeed, laparoscopic PALN sampling is technically feasible with regard to the absence of conversion to laparotomy and with acceptable operative time. No severe adverse event was reported. Moreover, we believe laparoscopic PALN sampling to be effective and consistent with published data on PALN sampling done by open surgical approach with regard to the median number of harvested LNs (n = 2, range [1–5]) and PALN involvement in FS (13%).⁵

From an oncological point of view, this approach allows an improvement in clinical practices in term of access to palliative care; the median time to the first chemotherapy cycle for patients with positive PALN was 10 days.

PALN involvement is commonly detected among patients with resectable pancreatic head carcinoma, with rates ranging from 8% to 26%.^{4,6,7,15–17} As others, we previously demonstrated that metastasis to LN16 implies systemic metastasis with regard to poor overall and disease-free survival (15.7 and 8.4 months, respectively).⁵ In that sense, when the biopsy samples obtained from para-aortic nodes are histologically positive, radical surgery with extended lymphadenectomy and soft tissue clearance should be abandoned.

Although noninvasive imaging is commonly used to identify most patients with unresectable PDAC, with regard to vascular involvement or liver metastases, a significant number (8% to 26%) of patients undergo invasive laparotomy only to discover that the disease is unresectable, due to PALN involvement. The risk of associated postoperative complications for exploratory laparotomy remains high (>30%), and this practice no longer corresponds to modern oncological and palliative care: fast access to chemotherapy, early rehabilitation, and quality of life.¹⁸

The WHO describes palliative care as the total active care of patients whose disease is not responsive to curative treatment. Management of psychological, social, and spiritual concerns but also control of symptoms is paramount. The goal of palliative care is to achieve the best quality of life for patients and their families.¹⁹

Hashimoto et al. suggested that staging laparoscopy, while avoiding laparotomy and unsuccessful resection, could lead to rapid induction of chemotherapy for unresectable PDAC.²⁰ In addition, Morris et al. reported better quality of life lasting up to 6 months with diagnostic laparoscopy in comparison with direct laparotomy due to the negative impact of unnecessary laparotomy.²¹ Finally, Beenen et al. proposed full minimally invasive management with regard to quality of life, for patients with unresectable PDAC found at staging laparoscopy, especially in an era of self-expandable metal stents with low axial force and flared ends.²² Staging laparoscopy is now largely admitted in oncosurgical practices, to avoid futile laparotomy.^23,24

The main postoperative risk in the setting of LN sampling is chyle leak. Several studies have demonstrated equivalence between several surgical ultrasonic or bipolar energy devices with regard to tissue sealing.^25–27 Tanaka et al.²⁸ evaluated the burst pressure (defined as the maximum pressure before leakage of the sealed vessels) and performed histological analyses of the sealed vessels by comparing ultrasonic devices and combined ultrasonic and bipolar energy device. Although a broader histological seal was observed using a device with combined ultrasonic and bipolar energies, no significant difference could be found for burst pressure. These results are consistent with the study of Milsom et al.²⁹ With regard to the efficacy of these ultrasonic and thermal (bipolar) energies in sealing lymphatics, there are fewer data available. Novitsky et al. demonstrated that the use of bipolar vessel sealer produced reliable and durable sealing of large lymphatic vessels in a porcine model.³⁰ At present there is no clear evidence to support the use of either advanced bipolar or ultrasonic devices in preference to other, especially in sealing lymphatics. It is likely that the surgeon will use several laparoscopic sources of energy (or hybrid instruments incorporating multiple technologies) depending on the personal preferences and their surgical experience.

Preoperative diagnosis of LN involvement in pancreatic cancer is hazardous,⁹ and LN size remains the most frequently used criterion, although not accurate on morphologic imaging.^10,11 Studies on the preoperative detection of LN involvement by imaging modalities have yielded disappointing results.¹⁷ In the study of Imai et al., all patients suspected of having PALN metastases on preoperative images had no histological confirmation, whereas 6 patients with no suspicion turned out to have PALN metastases.¹⁶ Although 18F-fluorodeoxyglucose (FDG)-PET has been reported to be superior to morphologic imaging as it provides functional data,³¹ the actual sensitivity of FDG-PET for LN metastases of pancreatic cancer has been reported to be between 46% and 71%, with a specificity ranging between 63% and 100%.¹⁶ These poor results do not justify its routine use to detect LN involvement, and systematic PALN sampling represents a more reliable intraoperative approach. In our opinion, systematic PALN sampling should be recommended, and a laparoscopic approach should be standardized.

Conclusion

Staging laparoscopy is already a standardized technique and is usually carried out, but associated laparoscopic PALN sampling has never been reported until now.

We report the feasibility and safety of laparoscopic PALN sampling and suggest its systematic realization during staging laparoscopy as a first step in patients with localized PDAC before pancreaticoduodenectomy.

Footnotes

Acknowledgments

The authors are grateful to Nikki Sabourin-Gibbs, Rouen University Hospital, for editing the article. None of the authors receive financial support.

Disclosure Statement

No competing financial interests exist.

Supplementary Material

References

Neoptolemos

, Palmer

, Ghaneh

, et al. Comparison of adjuvant gemcitabine and capecitabine with gemcitabine monotherapy in patients with resected pancreatic cancer (ESPAC-4): A multicentre, open-label, randomised, phase 3 trial. Lancet, 2017; 389:1011–1024.

Neoptolemos

, Stocken

, Tudur Smith

, et al. Adjuvant 5-fluorouracil and folinic acid vs observation for pancreatic cancer: Composite data from the ESPAC-1 and -3(v1) trials. Br J Cancer, 2009; 100:246–250.

Oettle

, Post

, Neuhaus

, et al. Adjuvant chemotherapy with gemcitabine vs observation in patients undergoing curative-intent resection of pancreatic cancer: A randomized controlled trial. JAMA, 2007; 297:267–277.

Japan Pancreas, Society. Classification of Pancreatic Carcinoma. 1st English ed. Tokyo, Japan: Kanehara, 1996.

Schwarz

, Lupinacci

, Svrcek

, et al. Para-aortic lymph node sampling in pancreatic head adenocarcinoma. Br J Surg, 2014; 101:530–538.

Shimada

, Sakamoto

, Sano

, Kosuge

. The role of paraaortic lymph node involvement on early recurrence and survival after macroscopic curative resection with extended lymphadenectomy for pancreatic carcinoma. J Am Coll Surg, 2006; 203:345–352.

Yoshida

, Matsumoto

, Sasaki

, et al. Outcome of paraaortic node-positive pancreatic head and bile duct adenocarcinoma. Am J Surg, 2004; 187:736–740.

Yamada

, Nakao

, Fujii

, et al. Pancreatic cancer with paraaortic lymph node metastasis: A contraindication for radical surgery?. Pancreas, 2009; 38:e13–7.

Soriano

, Castells

, Ayuso

, et al. Preoperative staging and tumor resectability assessment of pancreatic cancer: Prospective study comparing endoscopic ultrasonography, helical computed tomography, magnetic resonance imaging, and angiography. Am J Gastroenterol, 2004; 99:492–501.

10.

de Bondt

, Nelemans

, Hofman

, et al. Detection of lymph node metastases in head and neck cancer: A meta-analysis comparing US, USgFNAC, CT and MR imaging. Eur J Radiol, 2007; 64:266–272.

11.

Karmazanovsky

, Fedorov

, Kubyshkin

, Kotchatkov

. Pancreatic head cancer: Accuracy of CT in determination of resectability. Abdom Imaging, 2005; 30:488–500.

12.

Pietryga

, Morgan

. Imaging preoperatively for pancreatic adenocarcinoma. J Gastrointest Oncol, 2015; 6:343–357.

13.

Tempero

, Malafa

, Al-Hawary

, et al. Pancreatic Adenocarcinoma, Version 2.2017, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw, 2017; 15:1028–1061.

14.

Ducreux

, Cuhna

, Caramella

, et al. Cancer of the pancreas: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol, 2015; 26 Suppl 5:v56–68.

15.

Doi

, Kami

, Ito

, et al. Prognostic implication of para-aortic lymph node metastasis in resectable pancreatic cancer. World J Surg, 2007; 31:147–154; Sakai M, Nakao A, Kaneko T, et al. Para-aortic lymph node metastasis in carcinoma of the head of the pancreas. Surgery 2005;31:606–611.

16.

Imai

, Doi

, Kanazawa

, et al. Preoperative assessment of para-aortic lymph node metastasis in patients with pancreatic cancer. Int J Clin Oncol, 2010; 15:294–300.

17.

Kayahara

, Nagakawa

, Ohta

, et al. Analysis of paraaortic lymph node involvement in pancreatic carcinoma: A significant indication for surgery?. Cancer, 1999; 85:583–590.

18.

Lesurtel

, Dehni

, Tiret

, et al. Palliative surgery for unresectable pancreatic and periampullary cancer: A reappraisal. J Gastrointest Surg, 2006; 10:286–291.

19.

Organization

. WHO Definition of Palliative Care. Available at: www.who.int/cancer/palliative/definition/en (accessed March 5, 2019).

20.

Hashimoto

, Chikamoto

, Sakata

, et al. Staging laparoscopy leads to rapid induction of chemotherapy for unresectable pancreatobiliary cancers. Asian J Endosc Surg, 2015; 8:59–62.

21.

Morris

, Gurusamy

, Sheringham

, Davidson

. Cost-effectiveness of diagnostic laparoscopy for assessing resectability in pancreatic and periampullary cancer. BMC Gastroenterol, 2015; 15:44.

22.

Beenen

, van Roest

, Sieders

, et al. Staging laparoscopy in patients scheduled for pancreaticoduodenectomy minimizes hospitalization in the remaining life time when metastatic carcinoma is found. Eur J Surg Oncol, 2014; 40:989–994.

23.

Allen

, Gurusamy

, Takwoingi

, et al. Diagnostic accuracy of laparoscopy following computed tomography (CT) scanning for assessing the resectability with curative intent in pancreatic and periampullary cancer. Cochrane Database Syst Rev, 2016; 7:CD009323.

24.

De Rosa

, Cameron

, Gomez

. Indications for staging laparoscopy in pancreatic cancer. HPB (Oxford) 2016; 18:13–20.

25.

Gie

, Matthey-Gie

, Marques-Vidal

, et al. Impact of the Ultrasonic scalpel on the amount of drained lymph after axillary or inguinal lymphadenectomy. BMC Surg, 2017; 17:27.

26.

Matthey-Gie

, Gie

, Deretti

, et al. Prospective randomized study to compare lymphocele and lymphorrhea control following inguinal and axillary therapeutic lymph node dissection with or without the use of an ultrasonic scalpel. Ann Surg Oncol, 2016; 23:1716–1720.

27.

Seehofer

, Mogl

, Boas-Knoop

, et al. Safety and efficacy of new integrated bipolar and ultrasonic scissors compared to conventional laparoscopic 5-mm sealing and cutting instruments. Surg Endosc, 2012; 26:2541–2549.

28.

Tanaka

, Gitelis

, Meiselman

, et al. Evaluation of vessel sealing performance among ultrasonic devices in a porcine model. Surg Innov, 2015; 22:338–343.

29.

Milsom

, Trencheva

, Monette

, et al. Evaluation of the safety, efficacy, and versatility of a new surgical energy device (THUNDERBEAT) in comparison with Harmonic ACE, LigaSure V, and EnSeal devices in a porcine model. J Laparoendosc Adv Surg Tech A, 2012; 22:378–386.

30.

Novitsky

, Rosen

, Harrell

, et al. Evaluation of the efficacy of the electrosurgical bipolar vessel sealer (LigaSure) devices in sealing lymphatic vessels. Surg Innov, 2005; 12:155–160.

31.

Kauhanen

, Komar

, Seppanen

, et al. A prospective diagnostic accuracy study of 18F-fluorodeoxyglucose positron emission tomography/computed tomography, multidetector row computed tomography, and magnetic resonance imaging in primary diagnosis and staging of pancreatic cancer. Ann Surg, 2009; 250:957–963.

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