Laparoscopic Enucleation of Pancreatic Neoplasms: A Single-Center Experience and Outcomes

Abstract

Background:

Laparoscopic technique has been increasingly applied in the treatment of selected pancreatic tumors. The aim of this study is to evaluate the experience with laparoscopic enucleation of pancreatic neoplasms (LEPNs), for selected pancreatic diseases, at a high-volume referral center.

Methods:

Between May 2012 and October 2020, LEPNs was attempted in 16 patients with selected pancreatic neoplasms. The localization of tumors, etiology, indications, and clinical outcomes were analyzed.

Results:

Sixteen patients were included. LEPN was successfully performed in 13 patients, 3 conversions to open procedure were required. The definitive histopathological result of the resected pieces showed prevalence of intraductal papillary mucinous neoplasms. Postoperative major complications occurred for 3 patients (18.7%), the 3 of them presented postoperative pancreatic fistula (POPF). The median hospital stay was 4.5 days (range 2–7) for patients without POPF and 14.6 days (3–30) for those who presented with POPF. No deaths were registered. During a median follow-up of 43.8 months (0.2–109), no new-onset exocrine or endocrine insufficiency was diagnosed, no patient experienced tumor recurrence and, the 4 patients who underwent LEPN for insulinoma, remained asymptomatic.

Conclusion:

LEPNs has become a valuable alternative for patients with benign or low risk of malignancy tumors. Appropriate preoperative imaging is key for localization. Whenever feasible, this technique not only reduces the risks of exocrine and endocrine insufficiency, but also adds the well-known advantages of minimally invasive techniques, making it a safe and feasible treatment.

Introduction

Open procedures such as pancreatoduodenectomy and distal pancreatectomy are well-known techniques for the treatment of pancreatic neoplasms. Although they usually offer appropriate oncological results, these procedures represent a significant loss of pancreatic parenchyma and could contribute to both endocrine and exocrine pancreatic insufficiencies. These complications truly affect patients' quality of life and become especially undesirable in patients with benign or premalignant lesions.^1,2

Pancreatic enucleation (PE), as a parenchymal sparing surgery, reduces the loss of healthy parenchyma, decreasing the probability of insufficiency complications. Moreover, it enables preservation of the spleen and its immunological role.³ Therefore, it is rapidly becoming the preferred surgical option for a wide spectrum of pancreatic neoplasms, such as intraductal papillary mucinous neoplasms (IPMNs), neuroendocrine tumors (pNETs), serous cystadenomas (SCN) and mucinous cystadenomas (MCN), and solid pseudopapillary neoplasms (SPNs).^4,5

In the rise of minimally invasive surgery, laparoscopic enucleation of pancreatic neoplasms (LEPNs) is considered an ideal procedure, combining the advantages of both techniques.^6,7 However, laparoscopic approach to the pancreas still represents a challenge, even for specialized surgeons.

Overall, the LEPN experience is still poor and so its role remains uncertain. To analyze indications, techniques, and outcomes of LEPNs, we carried out a retrospective study for selected pancreatic diseases, at our institution over an 8-year period.

Patients and Methods

Patients

Patients who underwent LEPNs, by the hepatopancreatobiliary section of our institution between May 2012 and October 2020, were identified. All data were retrospectively collected using our institutional electronic medical records and stored in a remote database. Demographic, clinical, operative, and postoperative data were collected.

For preoperative clinical staging, transabdominal ultrasonography (US) and contrast-enhanced computed tomographic (CT) scan were first recommended for all patients, with the aim of localizing the tumors and identifying possible malignant disease.

In cases of cystic neoplasms, subsequently, magnetic resonance cholangiopancreatography (MRCP) was performed to clarify the tumor's relationship with the main pancreatic duct (MPD), pancreatic parenchyma, neighboring soft tissues, and vascular network. Moreover, MRCP and endoscopic ultrasonography (EUS) with or without fine-needle aspiration (FNA) were mainly indicated to differentiate IPMN from other cystic lesions and to evaluate possible “worrisome features.”⁸ Only patients with negative Sendai criteria were considered for enucleation.

Hyperinsulinism was diagnosed by clinical symptoms and biochemical analysis.

The patient selection criteria were based on the following characteristics of the tumor: size of the lesion ≤0 mm, a distance from the MPD of at least 2–3 mm, and no evidence of malignancy.⁹

It is important to highlight that the decision of performing LEPNs was always taken during the preoperative step by a multidisciplinary board.

The IRB approval or waiver statement criteria from 45 CFR 461[Sec.116(d)] have been met based on:

1. The research involves minimal risk, as the review of subjects' medical records is for limited information. The information is not sensitive in nature, and the data are derived from clinically indicated procedures. There is an extremely low probability of harm to subjects' status, employment, or insurability. The precaution taken to limit the record review to specified data and double coding of the data further minimize the major risk, which is breach of confidentiality. Contacting subjects to obtain their consent could be considered an invasion of privacy and cause subjects undue anxiety.

2. The rights and welfare of the individual would not be adversely affected because the clinically indicated surgical procedure and the associated blood chemistry values were already completed, or would be completed, regardless of the research. None of the results of the research would affect the clinical decisions about the individual's care because the results are analyzed after the fact. Subjects are not deprived of clinical care to which they would normally be entitled.

3. The research could not be practicably carried out without a waiver. Identifying and contacting the thousands of potential subjects, although not impossible, would not be feasible for a review of their medical records for information that would not change the care they would have already have received.

4. It would not be appropriate to provide these subjects with information about the results of the research as the results would have no affect on the subjects. The surgical procedure and postsurgical care have both been completed for these subjects. There is no anticipated benefit to subjects that would change what has already occurred.

Surgical technique

The technique of LEPNs has already been described in several studies.¹⁰ Patients are placed in a supine position. The laparoscopic approach requires four trocars, with the surgeon on the right side of the patient, with the first assistant. Through a window in the gastrocolic ligament, created using Hook cautery or an ultrasonic device (Ultracision, Johnson & Johnson, Cincinnati, OH), the body and the tail of the pancreas are exposed. The head of the pancreas is exposed by dissection of the mesocolic attachment, using a Nathason liver retractor (Nathanson Liver Retractors, COOK MEDICAL, Bloomington) for this maneuver.

A Kocher maneuver must be performed to explore the posterior surface of the head. An ultrasonic examination of the pancreas is performed with a laparoscopic US (L44LA intraoperative probe, 13-2 MHz, 36 mm; Hitachi, Tokio, Japan) to appropriately locate the tumor. Dissection is performed and the vessels of the tumor are secured with clips. A single drain is left.

Postoperative course

Clavien–Dindo classification was used to graduate postoperative morbidity. Grades III–V were considered as major complications.¹²

Following the International Study Group of Pancreatic Fistula (ISGPF) last report,¹¹ postoperative pancreatic fistula (POPF) was defined as a drain output of any measurable volume of fluid with an amylase level greater than three times the upper limit of normal amylase, on or after postoperative day 3, associated with a clinically relevant development; if it has no clinical impact, no fistula should be reported. In our institution, we have protocolized the management of the measurement of drainage amylase; on the 3rd postoperative day we take a sample of the abdominal drainage and measure the amylase.

If it is lower than three times the upper limit of normal serum amylase activity, we remove the drainage; if not, we repeat the procedure 48 hours later, if now the result is lower, we remove the drainage, otherwise the patient is discharged with it. On follow-up, the drainage will be removed according to its daily debit volume, patient's symptoms, and the result of a CT performed to exclude residual collections.

In the case of grade B or C fistulas, medical management has to be multidisciplinary, taking into account the patient's general condition, symptoms, CT results, etc. Each case must be individually approached.

Operative mortality was defined as any death, occurring within 30 days after surgery in or out of the hospital or after 30 days subsequent to the operation.

Patient follow-up included clinical evaluation and blood test 7–10 days after discharge, and then subsequently after 1, 3, and 6 months.

Surgery outcomes were also measured with an imaging study: US every 6 months and MRCP 1 year after treatment or earlier if recurrence was suspected.

Exocrine and endocrine postoperative functions were analyzed. The presence of new-onset or worsening diabetes was diagnosed considering blood glucose levels. The requirement of oral pancreatic enzymes defined new-onset exocrine insufficiency. There is no gold standard available for diagnosis, easy to apply in daily clinical practice, but when available fecal elastase (EF) test constitutes a rapid and economic diagnostic method (EF <200 mcg/g is a sign of exocrine pancreatic insufficiency).¹³

Statistical analysis

Data were analyzed using STATA MP -13 (Statacorp LLC, TX, EEUU). Numerical data are shown as a standard deviation, or median and range when appropriate. χ² or Fisher's exact test was used to compare categorical variables. However, an independent sample t-test was used for continuous variables. A P-value of ≤.05 was considered statistically significant, with a 95% confidence interval.

Results

A total of 16 patients underwent LEPNs during the study period. Patient characteristics are presented in Table 1. The mean age of patients was 49 ± 16 years. In total, 5 out of 16 (31%) were men. Twelve patients (75%) were asymptomatic, and their pancreatic lesion was discovered incidentally. The 4 remaining patients presented with symptomatic hypoglycemia. Two patients had preoperative diabetes mellitus.

Table 1.

Baseline Patients Characteristics

Age (year)	49.7 (CI: 38–63)
Gender (male/female)	5/16
Mean BMI	27.8 (CI: 26.1–29)
Comorbidity
Type 2 diabetes	2 (12.5%)
Cardiopulmonary disease	4 (25%)
Symptoms
Yes	4 (25%)
No	12 (75%)
Diagnostic technique
MRCP	14 (87.5%)
Ecoendoscopy	5 (31%)
CT	16 (100%)

BMI, body mass index; CI, confidence interval; CT, contrast-enhanced computed tomographic; MRCP, magnetic resonance cholangiopancreatography.

CT scan and/or MRCP was used for preoperative evaluation. EUS-FNA was required for 5 patients (31.2%), indicated to differentiate IPMN from other cystic lesions and to evaluate possible “worrisome features.”

After laparoscopic exploration, conversion to open surgery was required for 3 patients (18.7%), because of inability to locate the tumor; despite that, enucleation was successfully performed. The mean duration of surgery was 182 ± 69 minutes with minimal blood loss, requiring no blood transfusion.

The tumor was most frequently located in the head/neck of the pancreas [11 patients (68.7%)]. The mean diameter of the resected lesions was 1.6 ± 1 cm. The final histopathological results showed prevalence of pNETs. Details on histopathology are described in Table 2. Surgical margins were negative in all patients.

Table 2.

Surgical Outcomes

Open conversion	3 (18.7%)
Operating time (minutes)	182.2 (CI: 120–210)
Tumor location
Head–neck	11 (68.7%)
Body	3 (18.7%)
Tail	2 (12.5%)
Mean size	1.6 cm (CI: 0.6–2.6)
Type of tumor
IPMN	MD-IPMN 1 (6.3%) BD-IPMN 5 (31.3%)
pNET	Insulinoma 4 (25%)
pNET	Nonfunctional 3 (18.7%)
Serous cystadenoma	3 (18.7%)
Negative margins	16 (100%)

BD-IPMN, branch duct intraductal papillary mucinous neoplasms; CI, confidence interval; IPMN, intraductal papillary mucinous neoplasms; MD-IPMN, main duct intraductal papillary mucinous neoplasms; pNET, pancreatic neuroendocrine tumor.

Postoperative major complications occurred in 3 patients (18.7%), the 3 of them presented POPF (grade B for 1 patient and grade C for 2 patients) and were readmitted to hospital: 1 patient required intravenous antibiotics, 1 patient required an emergency angiography, and 1 patient presented multiple complications requiring an exploratory laparoscopy, a new percutaneous drainage, and two emergency angiographies. The mean length of hospital stay was 4.5 days (range 2–7) for patients without POPF and 14.6 (3–30) days for patients with POPF. No deaths were registered during the analyzed period, Table 3.

Table 3.

Postoperative Outcomes

Postoperative hospital stay (days):	Patients with fistula 14.6 (3–30) without fistula 4.5 (2–7)
Overall complications
Minor complications (grade I–II)	4 (28.6%)
Major complications (grade III)	3 (18.7%)
Pancreatic fistula	3 (18.7%)
Grade B	1 (33%)
Grade C	2 (66%)
Readmission	4 (28.6%)
Cardiopulmonary complication	1 (6%)
Emergency angiography	2 (12.5%)
Reoperation	1 (6%)
Percutaneous drainage	1 (6%)
Mortality	0
Follow-up (months)	43.8 (0.2–109)

During a median follow-up of 43.8 months (0.2–109), no patient experienced tumor recurrence, new-onset exocrine, or endocrine insufficiency. The 4 patients diagnosed with insulinoma remained asymptomatic.

Discussion

Pancreas surgery still represents one of the most challenging areas of gastrointestinal surgery, associated with up to a 50% morbidity and 5% mortality.^14,15 Nowadays, several pancreatic lesions are treated with parenchyma-sparing techniques.^3,16 The main benefit is to achieve a reduction in the risk of developing both exocrine and/or endocrine postoperative insufficiency.^4,17,18 Whenever feasible, LEPNs, as a parenchyma-sparing approach, not only decreases the probability of insufficiency complications, but also has the potential benefit of minimizing the risks of anastomosis complications and blood loss.

It also reduces operative time and postoperative hospital stay. Although this technique was initially described by Gagner et al.,¹⁹ owing to the few pancreatic neoplasms suitable for LEPNs, articles reported in the literature are rare, as given in Table 4. In this study we reported our experience, showing that LEPNs is a feasible and safe procedure for the treatment of selected cases of benign or low risk of malignancy tumors.

Table 4.

Main Published Series of Laparoscopic Pancreatic Enucleation

Author	Year	n	Conversion rate	POPF	Morbidity	Mortality	Pancreatic exocrine or endocrine insufficiency
Ayav et al.²³	2005	19	30%	NA	42%	0	NA
Luo et al.²⁰	2009	16	7.7%	25%	NA	0	0
Dedieu et al.⁴⁰	2011	23	8.7%	13%	17%	4%	0
Costi et al.²⁹	2013	25	12%	32%	56%	0	NA
Choi et al.⁷	2014	11	0	9.1%	9.1%	0	0
Zhang et al.³²	2016	15	6.7%	20%	20%	0	0
Cienfuegos et al.¹⁸	2017	36	0	8.3%	16.6%	5.5%	11%
Xu et al.	2020	66	4.5%	19.7%	24.2%	NA	NA
Present study	2021	16	18.7%	18.7%	18.7%	0	0

NA, not apply; POPF, postoperative pancreatic fistula.

PE has become the standard treatment of pNETs.²⁰ Other indications are SCN and MCN, SPN, and IPMN.^16,21 Among our patients, pNETs were the most frequent indication (43.7%), followed by IPMN (37.3%).

Contrary to an open approach, laparoscopic surgery lacks manual palpation, which is why adequate preoperative localization is crucial.²² In our experience, CT complemented with MRCP is the best imaging method to characterize the lesion. MRCP allows us to measure the distance between a lesion and the MPD and evaluate possible “worrisome features” in the case of IPMN.^3,8,23 Five of our patients required EUS-FNA. EUS allows high-resolution imaging of the pancreas. It detects mural thickening, nodules, microcalcifications, and communication with the MPD, among others, which may not be visible on imaging studies. EUS-FNA can provide additional information.

Among the tumor markers measured in the cyst fluid, carcinoembryonic antigen (CEA) has the highest value. A very low CEA level (<5) is highly suggestive of a serous cystadenoma, whereas a high value (>800) outlines more toward a cystadenocarcinoma.²⁴ In contrast, high amylase levels evidence communication with the Wirsung duct.²⁵ Intracystic glucose sampling may also be measured to help in the diagnosis of mucinous cystic neoplasms. McCarty et al. had recently published a systematic review and meta-analysis to evaluate the diagnostic performance of intracystic glucose and reported a cutoff of <50 mg/dL to be associated with mucinous cystic neoplasms.²⁶

In contrast to other groups, we consider intraoperative ultrasonography (IOUS) key for locating the tumor and to guarantee that a safe distance between the tumor and the MPD is preserved, otherwise LEPNs might be contraindicated.^27,28

In this series, LEPNs was achieved successfully in 13 patients, 3 patients (18.7%) required a laparotomy because of inability to locate the tumor, similar numbers are shown in other reported series.^23,29

In support of previous studies,^7,30,31 our experience confirmed that LEPNs could benefit patients with reduced postoperative pain, shorter hospital stay, quicker recovery to normal activity, and better cosmetic appearances, as compared with the open approach.

There was no operative mortality in our series. POPF is the most common complication after enucleation as demonstrated in several studies, Table 4. Among our patients, we described an overall postoperative morbidity and POPF rate of 18.7%. Our 3 cases with POPF were readmitted to hospital. One was grade B and only required intravenous antibiotics. The surgery drainage was finally removed 47 days after surgery.

The 2 remaining cases presented a grade C POPF. One of them required an emergency angiography, on the 5th postoperative day, after showing changes in the drainage debit and hematocrit drop. Angiography showed a pancreatic branch in the proximal third of the splenic artery with altered morphology, in relation to a surgical site hematoma; it was embolized with coils. The patient presented a favorable evolution after the procedure and the drainage was removed after 60 days.

The last case was the most complex, since the patient presented a severe postoperative pancreatitis, having to be reoperated on the 4th day after surgery; non-pathological findings were evidenced, and the whole presentation was interpreted as part of a systemic inflammatory response syndrome.

Among other postoperative complications, a pulmonary embolism with the need of immediate anticoagulant treatment was developed; presented fever and a new percutaneous drainage had to be placed; required two emergency angiographies that evidenced a pseudoaneurysm of the pancreaticoduodenal branch of the gastric artery and an active gastroduodenal artery bleeding; in both cases embolization was performed. After 62 days the drainage was removed, and during a follow-up of 7 years, the patient had not presented any further complications.

Contrary to Zhang's results,³² our 3 cases were enucleations of tumors located in the head/neck region. Costi et al.²⁹ had already described poorer outcomes with right-sided procedures.

As mentioned, POPF is the most frequent complication after enucleation. Previous studies had reported that POPF rate after LEPNs was higher than after open surgery.³³ However, in our series we report a POPF rate of 18.7% that is lower than that reported in the media. These results are similar to other studies, like Dalla Valle et al.³⁴ who performed a systematic review >63 articles, showing a POPF incidence rate of 45.9% for the open approach and 28.5% for the minimally invasive approach.

Deficiencies in postoperative pancreatic function could truly affect patients' quality of life.^35–37 In our group, we observed no endocrine or exocrine pancreatic insufficiency after surgery, consonantly with several other studies. Moreover, during the follow-up, we have no tumor recurrences. This reflects that LEPNs is an adequate technique, as long as the criteria selection is followed and the definitive histopathological results do not reveal signs of malignancy. Beyond this observation, regular follow-up examinations are crucial to detect recurrence.^38–40

The main drawbacks of this study are the small size of the population and its retrospective nature; however, as already mentioned, most of the series are limited by a small sample size since the overall experience in LEPNs to date is still sparse. In contrast, our strengths are that the whole evaluation was performed in a single center, with patients treated with homogeneous criteria by the same group of surgeons.

Conclusion

LEPNs has become a valuable therapeutic alternative for patients with benign or low risk of malignancy lesions. Preoperative localization of the lesion should be performed with a combination of appropriate imaging modalities. Invariably, the addition of IOUS provides crucial information, and should be routinely used. Whenever feasible, this technique not only reduces the risk of exocrine and endocrine deficiency, but also adds the well-known advantages of minimally invasive approach, making it a safe and feasible option.

Footnotes

Declaration of Patient Consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Author's Contributions

All the authors have made substantial contributions to this article and have read and approved the attached version. None of them has any direct or indirect commercial financial incentive associated with the publication of this article and all the funding involved in this study has been provided by our institution. All authors have read and comply with the requirements set forth in instructions for authors. There has been no duplicate publication or submission elsewhere and the article is not under consideration by another journal. In addition, the information contained in these pages has not been published electronically. Subject to acceptance, the authors will transfer copyright to the publisher.

Disclosure Statement

There are no conflicts of interest. None of the authors has any direct or indirect commercial financial incentive associated with the publication of this article.

Funding Information

The author(s) received no financial support for the research, authorship, and/or publication of this article.

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