Sorin T Alexndrescu , ,, Andrei C Zlte , Rzvn T Grigorie , Mihne Ionescu , Irinel Popescu , c

a Fundeni Clinical Institute, Dan Setlacec Centre of General Surgery and Liver Transplantation, Sos. Fundeni nr. 258, sector 2, Bucharest, Romania

b Carol Davila University of Medicine and Pharmacy, Bucharest, Romania

c Titu Maiorescu University, Faculty of Medicine, Bucharest, Romania

To the Editor:

Many patients with tumors of the pancreatic head or of the ampulla of Vater require endoscopic manipulation of the duode- nal papilla in order to achieve tumor biopsy or for common bile duct stenting. These interventional endoscopy approaches may lead to acute pancreatitis. The iatrogenic acute pancreatitis will influ- ence the surgical strategy in patients scheduled for pancreatico- duodenectomy (PD). Due to the small number of cases, the surgical strategy in patients who require PD in the context of acute pan- creatitis has not been standardized. The most meaningful strategy is to postpone the operation until clinic, enzymatic and radiologic remission of the pancreatitis is achieved. Even when these crite- ria are fulfilled, sometimes, during laparotomy one can observe the persistence of steatonecrosis (small foci of necrosis of the fatty tis- sue around the pancreas) and edema of the pancreas. In such in- stances, because of the pancreatic stump pancreatitis, the risk of pancreato-jejunal/gastric (PJA/PGA) anastomosis postoperative leak is extremely high [1] . Therefore, avoidance of the pancreatic anas- tomosis during PD and the performance of an external drainage of the pancreatic stump may represent an option, assuming the for- mation of a deliberate external pancreatic fistula. Afterwards, the internalization of the fistula can be performed during a second op- eration, usually by a pancreato-jejunostomy (“two stage” PD) [2] .

Herein, we presented a “two-stage” approach in a patient with acute pancreatitis necessitating PD for adenocarcinoma of the am- pulla of Vater. As an innovation, internalization of the deliberate external pancreatic fistula (resulting from the first operation) was performed by a fistula-jejunostomy (FJS).

A 62-year-old female patient was diagnosed by computed to- mography (CT) scan and endoscopy with tumor of ampulla of Vater in another hospital. One month later the patient was referred to our HPB center for treatment. During hospitalization, another en- doscopy was performed, and a biopsy from the tumor was taken. After biopsy, the patient developed acute pancreatitis (amylase 2333 U/L, lipase 5558 U/L). CT scan revealed intermediate severity acute pancreatitis - Balthazar D: enlargement of the pancreas, in- flammatory changes in pancreas and peripancreatic fat, ill-defined single peripancreatic fluid collection (without pancreatic necrosis). Under conservative treatment, seven days later, the serologic level of amylase and lipase became normal, and the CT scan performed two weeks later revealed radiologic remission of the acute pan- creatitis. Pathologic examination of the biopsy specimen revealed a G2 periampullary adenocarcinoma. Thus, three weeks after the biopsy, in the context of serologic and radiologic remission of the acute pancreatitis, the patient underwent PD. During the laparo- tomy, acute pancreatitis with edema of the pancreatic tissue and steatonecrosis (foci of necrosis of the fatty tissue around the pan- creas were 2-4 mm in diameter - too small to be identified on CT scan) were observed. Thus, the PD (with hepaticojejunostomy and precolic gastrojejunostomy) was performed, but the pancreato- digestive anastomosis was postponed, due to the increased risk of fistula. A pig-tail catheter (10 Fr) was placed adjacent to the pan- creatic stump, in order to achieve a deliberate external pancreatic fistula. The hepaticojejunostomy was performed at 25 cm from the cut-edge of the small bowel, preserving this bowel length for fu- ture anastomosis between the pancreas and jejunum. The postop- erative course was uneventful, and the patient was discharged on the 16th postoperative day (POD) with an external pancreatic fis- tula, drained through the pig-tail catheter. Oral intake of pancreatic enzyme supplements was recommended.

Pathologic examination of the PD specimen revealed a G2 ade- nocarcinoma of the ampulla of Vater (pT3pN1M0), acute inflam- mation and edema of the pancreas, as well as necrosis of the fatty tissue around the pancreatic head.

Although the patient did not present any sign of sepsis, the on- cologist was reluctant to give adjuvant chemotherapy due to the external pancreatic fistula. The 3- and 6-month follow-up CT scan did not reveal local recurrence or metastatic disease and the serum levels of CEA and CA 19-9 were within normal ranges.

Fig. 1. The performance of the posterior part of the fistula-jejunostomy with sepa- rate stitches.

Fig. 2. The fistula-jejunostomy completed.

Thus, six months after PD, a laparotomy was performed in order to internalize the external pancreatic fistula.

After laparotomy, the pig-tail drain served as a palpatory guide for identification of the fistula tract. The adhesions between the fistula tract (around the external drainage tube) and the small bowel and stomach were dissected. The fistula tract was transected at the level of the parietal peritoneum and the external part of the drain was cut-out. Because the thickness of the fistula tract was around 5 mm, we decided to perform a FJS. The jejunal stump (proximal to the hepaticojejunostomy) was identified and it was mobilized to allow the performance of a tension-free anastomosis between this jejunal loop and external pancreatic fistula.

An incision of the whole wall of the mobilized jejunal loop was done on its antimesenteric site, in order to perform the anasto- mosis. Four polydioxanone suture (PDS) 5.0 stiches were placed through the entire posterior wall of the fistula (from outside to inside) and then they were passed through the entire wall of the jejunum (from inside to outside) ( Fig. 1 ). Other two PDS 5.0 stiches were also placed in the same manner between the “corners” of the jejunal incision and fistula tract. The four stiches placed through the posterior wall were tied. The pig-tail drain was used for stent- ing the anastomosis (FJS). Thus, the drain was passed inside the jejunum through the incision performed before. Other four stiches were similarly placed through the anterior wall of the fistula and jejunum and were tied along with the two “corner” stiches ( Fig. 2 ). Two drains were placed near the FJS. The postoperative course was uneventful, and the patient was discharged on the 7th POD.

Two years after the performance of FJS, the patient is in a good clinical condition and disease-free.

It is reasonable for the patients with acute pancreatitis who re- quire PD to delay the resection until complete remission of acute pancreatitis. The timing of the operation should be based on the clinical status of the patient, as well as on the enzymatic and ra- diologic remission of the pancreatitis. Although these criteria were fulfilled in this case, there were still macroscopic signs of pancre- atitis at surgery, confirmed by microscopic examination (pathology report revealed steatonecrosis and edema of the pancreas). The de- lay of the PD was taken into account, but it raises also some con- cerns: (1) The timeline for complete pathologic remission of the pancreatitis could not be assessed based on clinical, enzymatic and radiological features, as long as the operation was performed more than one week after amylase, lipase and CT scan features became normal; thus, it would have been difficult to estimate the time of the next operation; (2) The timespan from the diagnosis of the tu- mor already exceeded 8 weeks, and a longer waiting time could increase the risk of progression to incurability (e.g., metastases de- velopment); (3) Postoperative immune dysfunction induced by la- parotomy could also contribute to tumor progression. By these rea- sons, it was decided to continue with PD.

Of course, this strategy implies some risks, of which the most frightening are abdominal sepsis (due to the contamination of the future pancreatic stump) and postoperative fistula of the pancreato-jejunal/gastric anastomosis (postoperative pancreatic fis- tula, POPF). Each of these conditions may lead to a hemorrhage [3] with fatal outcome in up to 54% of the patients [4] , due to the septic or enzymatic erosion of vascular structures (e.g., portal vein, gastro-duodenal artery stump, etc.). By avoiding the performance of pancreato-jejunal anastomosis, the risk of peritoneal cavity con- tamination with enteric content is ruled out, thus decreasing the risk of peritoneal sepsis. Furthermore, the intestinal juice composi- tion (enterokinase) is the cause of activation of pro-enzymes pro- duced by the pancreas (trypsinogen, chymotrypsinogen) into active enzymes able to produce lysis of the adjacent structures, mainly vascular structures. Thus, in the case of deliberate external pan- creatic fistula (without performing pancreato-jejunal anastomosis), the pancreatic pro-enzymes will not be activated, decreasing the risk of hemorrhage. By contrary, a fistula of the pancreato-jejunal anastomosis may lead to the leakage of intestinal juice in the peritoneum, activating proenzymes and increasing the risk of fatal bleeding. The above-mentioned conditions (POPF and abdominal septic foci) are more likely to occur in patients who undergo PD in the context of an acute pancreatitis [1] . Thus, the risk of devel- oping a clinically relevant POPF (grade B or C) is higher in patients presenting acute pancreatitis, than in those with normal pancre- atic tissue. By all the above-mentioned reasons, the performance of the PD associated with external drainage of the pancreatic stump (avoiding pancreatico-jejunal/gastric anastomosis) will lead to a biochemical leak (former grade A POPF), decreasing the risk of a grade B or C POPF [5] . Thus, the risk of developing postoperative fatal complications decreases dramatically, since the postoperative mortality rate after biochemical leak is almost 0, while in patients with grade B or C POPF requiring reoperation the mortality rate is as high as 37% [6] . Therefore, other authors considered that delay- ing the pancreato-enteric/gastric anastomosis for 3 to 10 months can represent a safe approach in selected high-risk patients [7] .

The second operation aimed the internalization of the external pancreatic fistula. The authors reporting such “two-staged” PD usu- ally fulfilled this goal by a pancreatico-enteric anastomosis [2 , 7] . However, by using this approach, more than 20% of the patients developed postoperative pancreatitis or pancreatic fistula after the second operation [7] . To avoid such complications that are due to the manipulation of the pancreas, a fistula-jejunostomy could be used for internalization of the external pancreatic fistula, instead of a pancreatico-enteric anastomosis [8-10] . The main advantages of this approach are represented by a less extensive dissection of the adhesions and the lack of pancreatic manipulation. Both advantages could improve outcome after the second operation. Nair et al. [9] and Luo et al. [10] reported no pancreatic leak after this operation. This type of pancreatic fistula internalization could also represent an attractive option in patients who develop persistent POPF after PD, in order to avoid extensive dissection around the previously performed pancreatico-jejunal anastomosis. This approach has been already described by Bassi et al. since 20 0 0 [8] in a patient with external pancreatic fistula after PD with pancreatico-jejunostomy.

In conclusion, to the best of our knowledge, this is the first case report in the literature of a patient with acute pancreatitis who underwent a scheduled “two-staged” PD with internalization of the deliberated external pancreatic fistula by fistula-jejunostomy. Such an approach could be taken into account in patients who need PD in the context of an acute pancreatitis.

CRediT authorship contribution statement

Sorin T Alexandrescu:Conceptualization, Supervision, Writ- ing - review & editing.Andrei C Zlate:Writing - original draft.Razvan T Grigorie:Writing - original draft.Mihnea Ionescu:Con- ceptualization.Irinel Popescu:Supervision, Validation.

Funding

None.

Ethical approval

This study was approved by the Ethical Committee of Fundeni Clinical Institute, Bucharest, Romania.

Competing interest

No benefits in any form have been received or will be received from a commercial party related directly or indirectly to the sub- ject of this article.