Duodenal neuroendocrine tumours in morbidly obese: Amalgamated strategy to optimise outcome.

The association of gastroenteropancreatic neuroendocrine tumours (GEP-NETs) with obesity has been reported and researched on. Rendering of a laparoscopic treatment treating these concurring pathologies in unison has not been described. Two morbidly obese patients with duodenal NETs underwent a resectional procedure, with curative intent, in the form of laparoscopic subtotal gastrectomy with roux-en-y gastrojejunostomy with partial duodenectomy and a laparoscopic one-anastomosis gastric bypass-mini gastric bypass with remnant gastrectomy and partial duodenectomy. Both patients had an uneventful convalescence with acceptable weight loss and no evidence of tumour recurrence on follow-up. The indolent nature of NETs, as compared to the morbidity of obesity provides the rationale for treating this particular cohort of patients with a surgical procedure that would serve to remove the tumour and also provide therapeutic benefit for obesity. With experience in advanced laparoscopic procedures, this can be accomplished safely with acceptable results.

INTRODUCTION

The gastroenteropancreatic neuroendocrine tumours (GEP-NETs) are a heterogeneous group of neoplasms with a variable biologic behaviour which have remained elusive with regards to the aetiology of the sporadic variant. The significance lies in the fact that it is the second most prevalent gastrointestinal tract (GIT) cancer after colorectal malignancies with an incidence of 7.4/100,000 population. Duodenal NETs (D-NETs) with an incidence of 1–2.5/100,000 population comprises 2%–5% of GEP-NETs and approximately 1%–3% of primary duodenal malignancies. NETs comprise approximately 1% of reported tumours associated with bariatric surgery.[1] There have been only a few isolated reports of D-NETs in obese patients who were anticipating a bariatric surgery. For the bariatric surgeon, it is imperative that the optimal treatment of these concurrent neoplastic and metabolic pathology be rendered to the patient in unison as cancer, in general, is not an absolute contraindication for bariatric surgery. We present a critical appraisal of literature and describe our experience of accomplishing this intended mode of treatment based on the philosophy of minimal access surgery for D-NETs in the setting of bariatric surgery.

METHODS

The study was approved by the institution's ethical committee. All patients entering the bariatric surgery program at our tertiary care centre undergo a standardised pre-operative evaluation by a multi-disciplinary team. A screening esophagoduodenoscopy (EGD) is performed in all patients to look for upper gastrointestinal lesions [Figure 1]. Two patients were found to have a duodenal lesion, which on histopathology revealed well-differentiated NET. The patients subsequently underwent further focussed evaluation to plan out the surgical procedure. Considering the patient characteristics (the altered physio-metabolic state of morbid obesity) and the concurrent neoplastic pathology [Table 1], it was decided to subject the patients to a resectional procedure which would remove the tumour and also serve a therapeutic purpose for morbid obesity. Patient-A underwent laparoscopic subtotal gastrectomy with roux-en-y gastrojejunostomy with partial duodenectomy removing the culpable segment of intestine en-bloc with the resected stomach [Figure 1]. Patient-B underwent laparoscopic one-anastomosis gastric bypass (OAGB-MGB) with remnant gastrectomy and partial duodenectomy. No lymphadenectomy was performed in view of the small size of tumour and no avid lesion suggestive of lymph node metastasis detected on whole-body positron emission tomography-computed tomography (PET-CT) with Gallium-68 DOTATATE scan (somatostatin analogue Tyr3-octreotate or TATE labelled with the PET tracer gallium-68 via the chelating agent dodecanetetraacetic acid). A comprehensive review of the literature was done searching the various online databases (PubMed, EMBASE, MEDLINE) with the following keywords-obesity, bariatric surgery, laparoscopic surgery, NETs, duodenal NETs, duodenal tumours, carcinoid tumours.

Figure 1

(a) Endoscopic image of one of the two patients showing the duodenal nodule. (b) Depiction of port placement for the laparoscopic procedure. (c) Intraoperative picture showing transection of the duodenum distal to the lesion with endostapler (Echelon 45 Endopath, Blue Load, Ethicon Endo-Surgery, Cincinnati, OH, USA). (d) Histopathology showing labelled Ki-67 antibody in the lesion (black arrow)

Table 1

Patient characteristics

Variable	Patient-A	Patient-B
Age	45	55
Sex	Female	Male
Height (cm)	160	170
Weight (kg)	117	122
BMI (kg/m2)	45.7	42.2
Co-morbidities	Hypertension Sleep apnoea	Hypertension
EGD findings	Small duodenal nodule in first part of duodenum	Small submucosal lesion in first part of duodenum
Dotanoc-PET CT findings	Dotanoc avid enhancing nodular lesion in first part of duodenum. No regional node or metastasis	Dotanoc avid enhancing lesion in first part of duodenum. No regional node or metastasis
Operative details
Procedure	Laparoscopic subtotal gastrectomy with roux-en-y gastrojejunostomy with partial duodenectomy	Laparoscopic one-anastomosis gastric bypass (OAGB-MGB) with remnant gastrectomy and partial duodenectomy
Blood loss (ml)	20	15
Post-operative complications	Vomiting off and on for 2 postoperative days	None
Length of stay	5 days	4 days
Histopathology examination
Size of tumour (cm)	0.8 × 0.8	1.5 × 1
Microscopic	Well-differentiated NET	Well-differentiated NET
Chromogranin-A	Positive	Positive
Ki-67 index (%)	2	3
Grade	1	2

BMI: Body mass index, EGD: Esophagogastroduodenoscopy, NET: Neuroendocrine tumours, PET: Positron emission tomography, CT: Computed tomography, OAGB-MGB: One-anastomosis gastric bypass-mini gastric bypass

RESULTS

Both patients had an uneventful post-operative recovery with no complication greater than Clavien-Dindo grade 1. Histopathology revealed a grade 1 and grade 2 well-differentiated NET respectively for the two patients [Figure 1]. Thirteen and 14 months post-operatively, percent of excess weight loss (%EWL) is 55% and 62% respectively, with no other symptoms or evidence of tumour recurrence.

DISCUSSION

Studies have documented the high incidence of NETs among the obese population conceivably due to the increased prevalence of preoperative endoscopic evaluation before bariatric surgery, increased physician awareness and contributory environmental factors. Certain biologic features of this neoplasm, namely, the association with obesity and metabolic syndrome, their low grade and indolent nature with majority (66%) having a low risk for regional nodal metastasis and their response to surgical intervention with an exceptional survival of >95% for Stage I D-NETs[2] lays the treatment foundation of this unique pathoneoplastic entity based on the philosophy of minimal invasive surgery.

Very few cases of GEP-NETs associated with bariatric surgery have been reported, with the predominant site being the stomach or ileum. Our search had shown two previous reports on D-NETs treated concomitantly, although, with non-laparoscopic approaches, in conjunction with a bariatric procedure.[34] Obesity increases the risk of several cancers and accounts for the genesis of up to 20% of all cancers. Metabolic syndrome is strongly associated with GIT cancers, including the NETs, in terms of greater severity and size of the tumour and Ki67% proliferation index. Chronic low-grade inflammation with the resultant effects of abnormal cytokine production and inflammatory signalling eventually leads to the genesis of obesity-related neoplasms.

Non-functioning NETs have significantly lower, and more size-dependent, local invasive potential. Fitzgerald et al.[2] reported a low risk for nodal metastasis for neoplasms less than 2 cm in size, not involving the muscularis propria. Neoplasms <1 cm and 1–2 cm not involving the muscularis propria had a 2% and 4.7% risk for nodal metastasis, respectively, while lesions >2 cm in size or involving the muscularis propria had a risk of 20.8% for regional nodal disease.[5]

A pre-operative EGD in a patient anticipating bariatric surgery is pivotal as a multitude of pathological findings may be encountered, which may have a bearing on the intended mode of surgical therapy. Studies including systematic review and meta-analysis show that a pre-operative EGD detects an abnormal finding in up to 56%–90% of cases resulting in a delay or change of surgical plan in up to 10% of these cases.[6] The American Society for Gastrointestinal Endoscopy, along with the Society of American Gastrointestinal and Endoscopic Surgeons and the American Society for Metabolic and Bariatric Surgery recommends that the decision to perform EGD before bariatric surgery should be personalised. Based on the significant proportion of findings, we believe that all bariatric patients must undergo an EGD preoperatively.

The presence of any neoplasm is unfortunate for a patient, but the presence of a D-NET in an obese patient is fortuitous considering the fact that a resectional procedure aimed at ameliorating both the problems in one shot may find preference in the mind of the surgeon. Active malignancy is not an absolute contraindication for bariatric surgery, and considering the risks associated with obesity and the fact that a bariatric procedure is less likely to hinder any future therapies,[5] it is advantageous to resect this indolent tumour as a component of the bariatric procedure. Span and Idress reported a D-NET in an obese patient wherein the envisioned treatment of endoscopic resection was aborted due to concern of deeper invasion[4] and an open procedure with duodenal resection in conjunction with vertical sleeve gastrectomy was done. In a series of ten patients with non-ampullary tumours including one NET, Stauffer et al. demonstrated successful laparoscopic partial sleeve duodenectomy as a modality of treatment precluding the morbidity of pancreaticoduodenectomy and averting an open incision.[7]

The duodenum has a thinner wall than the stomach and submucosal dissection may expose the duodenal wall to bile and pancreatic juice, making it vulnerable to perforation. A high perforation rate of 40%–67% was reported in a small case series describing ESD in duodenal carcinoid tumours.[8] Any such complication in the background of morbid obesity is expected to have a worse outcome and accordingly, prudence would be to extirpate the lesion surgically rather than endoscopically.

The clinical profile of the two patients with regard to their morbid obesity and associated co-morbidities merited a bariatric procedure that would have favourable long-term outcomes with minimal complications. A combined restrictive and malabsorptive procedure with some modification to accommodate the intention of resecting the associated tumour was ideally suited for the two patients. An OAGB-MGB procedure was chosen for patient-B specifically to address the voluminous and non-vegetarian nature of his diet. The execution of the concomitant gastro-duodenal resection with the intended bariatric procedure was accomplished in both cases without the need of extra ports and minimal extra time of approximately 40 min. As compared to an isolated bariatric procedure, these two extended procedures did not incur any additional morbidity or length of stay for the patients, achieved an acceptable %EWL and rendered the patient tumour-free. This highlights the advantage of a laparoscopic approach and establishes the safety and efficacy of a concomitant gastro-duodenal resection that can be undertaken to treat such patients.

CONCLUSION

The co-existence of the NET with obesity poses a challenge to the surgeon to deliver a treatment that remedies this distinctive pathoneoplastic entity. The indolent nature of the NET and the co-morbidity of obesity make surgical resection the most effectual treatment which would address both these issues. The practice of endoscopic evaluation before a bariatric procedure helps in planning out the most appropriate treatment. The possibility of an incomplete endoscopic removal of a lesion due to deeper invasion and the associated inherent risk of perforation alludes that surgical resection should be the treatment in this clinical situation. Complex laparoscopic resectional procedures for duodenal tumours can be safely accomplished, averting the need of a pancreaticoduodenectomy. The decision for a specific bariatric procedure in a patient can be taken on its own merits and the remnant gastrectomy along with duodenectomy of the first part of duodenum bearing the tumour with negative resection margins addresses the treatment of incidentally detected tumour adequately and safely.

Informed consent

Informed consent was obtained from all individual participants included in the study.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patients have given their consent for 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.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflict of interest.