Keywords
central pancreatectomy - pancreaticojejunal anastomosis - pNET
The uprising indications for abdomen computed tomography (CT) scan have led to increased
diagnosis of low or intermediate malignancy tumors in the past few years.[1] Neuroendocrine tumors of the pancreas (pNETs) constitute as a rare, heterogeneous
group of pancreatic neoplasms arising from the neuroendocrine system of the gut. It
is estimated that less than 3% of pancreatic tumors prove to be pNETs. They may coexist
with pituitary adenoma and parathyroid hyperplasia within the multiple endocrine neoplasia
type 1. pNETs are divided into two groups, functional (F-pNETs) and nonfunctional
(NF-pNETs) tumors and they appear to have a wide prognostic range, because they may
have benign, uncertain, or malignant behavior.[2] In 2010, World Health Organization (WHO) offered a histological classification of
pNETs, which were divided based on the Ki67% index into three groups: Grade I when
Ki67≤2%, Grade II when Ki67 = 3–20%, and Grade III when Ki67 > 20%, and this classification
was clinical validated to successfully predict metastases or recurrences.[3]
Therapeutically, pancreatoduodenectomy (PD) and distal pancreatectomy (DP) with or
without preserving the spleen have been used for the resection of benign or intermediate
malignancy tumors, such as pNETs. However, these techniques resulted in the resection
of a large portion of healthy pancreatic tissue, increasing the risk of pancreatic
endocrine and exocrine disfunction. Large population studies revealed that the incidence
of new-onset diabetes mellitus (NODM) and exocrine pancreatic insufficiency after
PG was up to 22.2 and 49.1%, respectively.[4] Also NODM occurrence ranges in 14–30.5% after DP.[5]
[6]
Furthermore, enucleation of benign lesion such as insulinomas has also been performed.
However, enucleation of tumors located at the pancreatic body is not always feasible,
because the tumors often infiltrate to the main pancreatic duct. As a result, an alternative
technique has been proposed, called central pancreatectomy (CP), for the resection
of solitary, small tumors located at the pancreatic neck or proximal body, which do
not need extended lymphatic clearance, preserving as much healthy pancreatic tissue
as possible.[7]
CP is a parenchyma-sparing segmental resection where the cephalic stump is sutured
or anastomosed to a Roux-en-Y jejunal loop—the distal stump is anastomosed to the
aforementioned loop or to the stomach. It was first performed in 1957 by Guillemin
and Bessot for a patient with pancreatitis[8] later it was performed by Letton and Wilson for severe traumatic injury of the pancreatic
body[9] and afterward it had limited use in trauma and benign conditions. CP had limited
use until 1998 that became apparent that CP had a place in pancreatic surgery for
benign or low-grade malignant tumors.[10] In 2008, a study regarding a single-center experience of 50 cases with low-grade
malignant neoplasms concluded that CP leads to effective preservation of both cephalic
and distal pancreatic remnants without a significant increase in postoperative morbidity
compared with conventional pancreatectomy.[11] A study in 2010 revealed that CP had lower rate of new-onset, lower rate of worsening
diabetes and decreased insulin requirements, compared to DP.[12]
Laparoscopic CP has been previously performed[13] and CP without anastomosis has also been reported, as an effective procedure with
lower morbidity and reduced length of hospital stay, compared with patients undergoing
CP with an anastomosis.[14]
It is of note that CP has been successfully performed for the treatment of various
conditions. Specifically, CP is indicated for the resection of intraductal papillary
mucinous neoplasm (IPMN), mucinous cystic neoplasm, serous cystadenomas, solid pseudopapillary
neoplasms and nonneoplastic cysts not suitable for enucleation, isolated metastases
to the pancreas, focal chronic pancreatitis with Wirsung's duct stenosis, and pancreatic
trauma.[15]
[16] An exception to these indications could be the IPMN of the main duct, due to the
difficulty of preoperative and intraoperative diagnosis of definite negative margins,
thus increasing the risk for recurrence.[7]
In the recent consensus guidelines update for the management of patients with pNETs,
surgical resection for NF-pNET is preserved for patients with tumors > 2cm and tumors < 2 cm
Grade II (based on proliferation index Ki67 <20%). Surgical intervention could be
enucleation or local resection, while more extended resections, such as PD and DP,
are reserved for selected cases.[17]
The objective of our study was to share the experience of our center in open CP with
pancreaticojejunal anastomosis (PJA) for pancreatic neck/proximal body NF NETs.
Materials and Methods
In 1 year, two male patients were admitted to our department with asymptomatic pancreatic
lesion, which was found incidentally on CT scan. Patient 1 was 77 years of age and
his medical history revealed arterial hypertension, hyperuricemia, diabetes mellitus
II (diagnosed 4 years ago), and carotid disease ([Table 1]). He was tested for gastrin, chromogranin A, adrenocorticotropic hormone (ACTH),
and growth hormone (GH) secretion and was found negative. Subsequently, magnetic resonance
imaging (MRI) and endoscopic ultrasound/fine-needle biopsy/pathological examination
were performed to determine the location, size, and proliferation index Ki67 of the
lesion. MRI revealed mass at the proximal pancreatic body of 1.45 cm in patient 1,
but the EUS revealed mass with size 1.7 × 1.4 cm ([Fig. 1]). Histopathological examination of biopsy taken from the EUS of the patient 1 revealed
pNET with Ki67 3 to 20% (Grade II).
Table 1
Clinical and postoperative data
|
Gender
|
Age
|
Medical history
|
Type of surgery—duration (min)
|
Duration of hospital stay (d)
|
Drainage amylase levels mean (min—max) IU/L
|
Duration of leakage (d)
|
Grade of fistulae[a]
|
|
Patient 1
|
M
|
77
|
AH, HU, DMII, carotid disease
|
CP with PJA (360)
|
18 (1st)
6 (2nd)
|
16,072 (1,568–38,823)
|
30
|
B
|
|
Patient 2
|
M
|
72
|
AF, sleep apnea, renal impairment
|
CP with PJA (445)
|
15
|
11869 (3,858–34,235)
|
20
|
Biochemical leak (former A)
|
Abbreviations: AF, atrial fibrillation; AH, arterial hypertension; CP, central pancreatectomy;
DM II, diabetes mellitus II; HU, hyperuricemia; PJA, pancreaticojejunal anastomosis.
a Based on 2016 revised criteria of the International Study Group on Pancreatic Fistula.
Fig. 1 (A) computed tomography and (B) endoscopic ultrasound of patient 1 showing the pancreatic lesion.
Patient 2 was 72 years of age and his medical history included atrial fibrillation,
sleep apnea, and renal impairment, without the need for dialysis ([Table 1]). His blood sample turned out to be negative for gastrin, chromogranin A, ACTH and
GH secretion, and the patient also had normal bilirubin levels. The MRI of patient
2 revealed hypervascular solid mass of proximal pancreatic body of 2.51 cm, compatible
with pNET, without pathological lymph nodes or apparent distant metastasis ([Fig. 2]). Since his lesion exerted the limit of 2 cm and based on the MRI characteristics,
it was decided to proceed with CP rather than enucleation, due to the high risk of
injuring the Wirsung's duct.[18]
Fig. 2 Magnetic resonance imaging showing the pancreatic lesion of (A) patient 1 and (B) patient 2.
As a result, both our patients exhibited NF pNET sized > 2cm or with proliferation
marker Ki67 < 20%; thus, they were fulfilling the criteria for segmental pancreatectomy.[17] Informed consent of the patients was obtained following a detailed explanation of
the procedure and the associated risks.
Results
Both our patients underwent CP with distal PJA with Roux-en-Y reconstruction. Regarding
the surgical technique, after Kocher maneuver, the posterior wall of pancreatic body
was detached from the superior mesentery vessels ([Fig. 3]) and the proximal body was resected, yielding 1 cm free of the lesion. The splenic
vessels were retained. The proximal remaining pancreas was primarily closed with hemostatic
sutures (horizontal mattress). Afterward, a jejunal loop was used for the creation
of a handmade end-to-side PJA with the distal end of the remaining pancreas in two
layers of sutures. At the same jejunal loop, just a few cm further of the anastomosis,
the head and neck of the pancreas were approximated using complementary sutures, as
a jejunal patch ([Fig. 4]). In both the patients, drain was placed near the PJA.
Fig. 3 During surgery, the posterior wall of pancreatic body is getting detached from the
superior mesentery vessels. Arrow indicates the lesion of patient 2.
Fig. 4 Creation of pancreaticojejunal anastomosis with jejunal patch (as indicated by the
arrow).
Pathology examination of patient 1 revealed pNET, sized 1.45 cm, Grade II. Histopathology
examination of the patient's 2 specimen confirmed the diagnosis of pNET Grade I with
lesion size 2.8 cm. In both the specimens, the margins were free.
Early postoperatively both patients exhibited signs of pancreatic fistula (PF) but
reoperation or interventional radiologic procedures were not required in any of them.
The fistulae of patients 1 and 2 were classified based on the 2016 revised criteria
of the International Study Group on Pancreatic Fistula as Grade B (persistent drainage
>3 weeks) and biochemical leak (former Grade A), respectively[19]
[20] ([Table 1]).
Specifically, patient 1 from the 1st postoperative day (POD) exhibited elevated amylase
levels from the abdominal drain (mean amylase 16,072 IU/L, ranged between 1,568 and
38,823 IU/L), with output less than 200 mL/day and leukocytosis until the 10th POD,
though he did not present with fever or hemodynamic instability. Patient 1 was discharged
on the 16th POD with the drain in place. The patient came back for follow-up on the
24th POD with mild abdominal discomfort and leukocytosis. CT scan was performed, which
identified small intraperitoneal fluid collection near the PJA (∼100 mL). Readministration
to the hospital was decided for broad-spectrum antibiotic (ciprofloxacin and metronidazole)
treatment. The patient had significant clinical improvement, and the drainage gradually
dropped to 20 mL/day. As a result, the drain was removed 6 days later, the patient
discharged on the same day, and he was in excellent physical condition during the
next follow-up visit.
On the other hand, patient 2 presented on the 1st POD with a biochemical leak with
amylase more than three time times of the upper limit of the normal serum amylase
(mean amylase from drainage 11,869 IU/L, ranged between 3,858 and 34,235 IU/L), with
output equal or less than 100 mL/day, without septic complications (fever, leukocytosis,
etc.). Otherwise his postoperative course was uncomplicated and he was discharged
on the 13th POD. He came back a week later (on the 20th POD) for clinical examination,
was found in good clinical condition and had his abdominal drain removed, since the
daily output was less than 20 mL/day.
After discharge, both patients were advised to get a thorough evaluation from an oncologist.
At 6 months follow-up, none of them was needed complementary administration of pancreatic
enzymes, none of them developed NODM II, and none of them had a recurrence of the
disease.
Discussion
CP compared with PD and DP showed significantly reduced mortality and lower rates
of postoperative deaths, making CP preferable for benign or low-grade malignant tumors.[21]
[22] As far as the function of the remaining pancreatic tissue is concerned, in a median
follow-up of 36 months after CP, the rates of new-onset exocrine and endocrine insufficiency
were 6 and 2%, respectively.[23]
In our study, none of our patients reported signs/symptoms of exocrine dysfunction,
such as steatorrhea, flatulence, weight loss, and/or other signs of unjustified malnutrition
and none of them reported NODM. It is worth mentioning that patient 1 already had
diabetes mellitus II, diagnosed several years prior to surgery and was under treatment
with vildagliptin, metformin/glimepiride. After surgery, he needed insulin to maintain
glucose control, though his glycemic control even before surgery was poor, as indicated
by high (ranged between 7.5 and 8.5%.) glycated hemoglobin A1c.
Regarding the surgical technique, we prefer pancreatectomy with PJA to pancreatogastric
anastomosis. Previous studies have shown that pancreatogastric anastomosis was associated
with higher risk of abdominal postoperative complications, such as abdominal collections
and PF.[24] On the other hand, a large meta-analysis concluded that there were no differences
regarding the rate of clinically significant PF, postoperative hemorrhage, or delayed
gastric emptying.[25]
In our study, none of our patients exhibit postoperative hemorrhage, but both presented
with PF; the first had only biochemical leakage and the other one developed Grade
B PF, without septic complications. In many studies, PF has been described as the
most common complication after CP, with an incidence variation up to 63%.[23]
[24] One explanation for this high prevalence of post-CP formation of PF lays to the
fact that CP has two points that might leak, the proximal head stump, which is “patched”
to the jejunum, and the distal one, which is anastomosed to the jejunal loop. Furthermore,
the anastomosis is performed on a soft pancreas usually with a normal diameter main
pancreatic duct, because of the benign or low-grade malignant tumors that constitute
indications for CP.[24]
With respect to the limitations issued by our small sample, we might conclude that
CP as a parenchyma-sparing technique could provide adequate, functional remaining
pancreatic tissue, because none of our patients developed NODM or needed pancreatic
enzymes supplements. Furthermore, small pancreatic leakage (Grade A or B) could be
treated conservatively and diminished automatically without septic complications.
In conclusion, CP with Roux-en-Y PJA and jejunal patch to the proximal pancreatic
stump might be considered as safe and effective technique for low or intermediate
malignancy tumors.
