Author Affiliations: Department of Hepatobiliary & Pancreatovascular Surgery, First Affiliated Hospital of Xiamen University; Oncologic Center of Xiamen, Xiamen 361003, China (Zhou YM, Wu LP, Su X and Li B); The 4th Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438, China (Zhang XF and Shi LH)

Corresponding Author: Bin Li, MS, Department of Hepatobiliary & Pancreatovascular Surgery, First Affiliated Hospital of Xiamen University, Xiamen 361003, China (Tel: 86-592-2139708; Fax: 86-592-2139908; Email: Binl1962@sina.cn)

 

© 2014, Hepatobiliary Pancreat Dis Int. All rights reserved.

doi: 10.1016/S1499-3872(14)60032-1

 

Contributors: ZYM and LB participated in the design and coordination of the study, carried out the critical appraisal of studies and wrote the manuscript. ZXF, WLP, SX and SLH developed the literature search, carried out the extraction of data, and assisted in the critical appraisal of included studies. All authors read and approved the final manuscript. LB is the guarantor.

Funding: None.

Ethical approval: This study was approved by the Ethics Committee of our hospital.

Competing interest: No benefits in any form have been received or will be received from a commercial party related directly or indirectly to the subject of this article.

BACKGROUND: Postoperative pancreatic fistula is one of the most common complications after pancreatectomy. This study aimed to assess the occurrence and severity of pancreatic fistula after central pancreatectomy.

 

METHODS: The medical records of 13 patients who had undergone central pancreatectomy were retrospectively studied, together with a literature review of studies including at least five cases of central pancreatectomy. Pancreatic fistula was defined and graded according to the recommendations of the International Study Group on Pancreatic Fistula (ISGPF).

 

RESULTS: No death was observed in the 13 patients. Pancreatic fistula developed in 7 patients and was successfully treated non-operatively. None of these patients required re-operation. A total of 40 studies involving 867 patients who underwent central pancreatectomy were reviewed. The overall pancreatic fistula rate of the patients was 33.4% (0-100%). Of 279 patients, 250 (89.6%) had grade A or B fistulae of ISGPF and were treated non-operatively, and the remaining 29 (10.4%) had grade C fistulae of ISGPF. In 194 patients, 15 (7.7%) were re-operated upon. Only one patient with grade C fistula of ISGPF died from multiple organ failure after re-operation.

 

CONCLUSION: Despite the relatively high occurrence, most pancreatic fistulae after central pancreatectomy are recognized a grade A or B fistula of ISGPF, which can be treated conservatively or by mini-invasive approaches.

 

(Hepatobiliary Pancreat Dis Int 2014;13:203-208)

 

KEY WORDS: pancreas; central pancreatectomy; pancreatic fistula

 

Postoperative pancreatic fistula is one of the most common complications after pancreatectomy, often resulting in intra-abdominal abscess and bleeding, wound infection, respiratory complications, sepsis, and prolonged postoperative hospitalization.^[1-16] Since the first report of central pancreatectomy (CP) in 1957, it has been increasingly used to remove benign or low-grade malignant tumors located in the neck and body of the pancreas. Unlike other conventional major pancreatic resections, CP has the advantages of preserving the integrity of the gastrointestinal tract and splenic function and sparing maximal pancreatic endocrine and exocrine function by avoiding extended resection of the pancreas.^[17-20] However, the high pancreatic fistula rate has been one of the major shortcomings of the procedure.^[20-23] The introduction of the International Study Group on Pancreatic Fistula (ISGPF) definition offers a standardized way to document pancreatic fistula related complications.^[16] This study aimed to assess the occurrence and severity of pancreatic fistula after CP.

 

 

The medical records of 13 patients who had undergone CP between January 2006 and July 2011 were retrospectively reviewed. Informed consent was obtained from these patients and the study was approved by the Ethics Committee of our hospital. In this series, 5 were men and 8 women, with a mean age of 42.1 years (27-64). Preoperative computed tomography and ultrasonography were routinely performed in all patients to determine the size and location of the tumors and to determine potential indications for CP.

 

Surgery was performed through a midline incision at the upper abdomen to open the lesser sac and expose the anterior face of the pancreas by dividing the adhesion between the posterior surface of the stomach and the pancreas. The pancreatic lesion was resected using electrocautery with a margin of at least 1 cm to cut both sides of the pancreas. Specimens taken from surgical margins were frozen and assessed intraoperatively. The proximal pancreatic stump was over-sewed with interrupted non-absorbable 4-0 suture after ligation of the identified main pancreatic duct. The distal pancreatic stump was reconstructed by retrocolic end-to-side dunking Roux-en-Y pancreaticojejunostomy. Before abdominal closure, an intra-abdominal drainage tube was placed around the surgical field.

 

A literature search was performed using PubMed database from 1966 to June 2012. Search terms were "central pancreatectomy", "medial pancreatectomy", "middle segment pancreatectomy", and "median pancreatectomy". Only studies with at least five cases of CP published in the English language were included. Letters, reviews, abstracts, editorials, expert opinions, non-English language papers and animal studies were excluded. In the case of multiple publications of a given cohort of patients, only the most recent one was used.

 

Two investigators (ZYM and ZXF) independently reviewed all the retrieved studies that met the inclusion and exclusion criteria. Discrepancies between the two reviewers were resolved by discussion and consensus. The two reviewers extracted data on the following categories: first author, year of publication, study design, patient demographic characteristics, incidence and severity of pancreatic fistula. Pancreatic fistula was defined and graded according to the recommendations of the ISGPF.^[16]

 

 

The mean operative time of the 13 patients was 186 minutes (160-280), and the mean intraoperative blood loss was 450 mL (100-1600). Three patients required blood transfusion. The spleen was preserved in all patients.

 

There was no death. Eight of the 13 patients developed postoperative complications. Pancreatic fistula was the main complication, occurring in 7 patients. According to the ISGPF definition, all the 7 patients with pancreatic fistula belonged to grade B. Of these patients, 5 patients with fistulae were managed by delayed removal of surgical drains. Two fistulae with intra-abdominal fluid collection were managed by percutaneous drainage with total parenteral nutrition. No patient required re-operation. The mean length of hospital stay was 26 days (14-47).

 

Final pathology revealed 6 patients suffered from serous cystadenoma, 3 from mucinous cystadenoma, 2 from branch-duct intraductal papillomary-mucinous neoplasms, 1 from nonfunctioning islet cell adenoma, and 1 from chronic pancreatitis. All resection margins were microscopically negative. No patient developed new onset diabetes or exocrine pancreatic insufficiency during a median follow-up period of 17 months (6-64). One patient with chronic pancreatitis had preoperative diabetes, which did not worsen after surgery. There was no neoplastic recurrence.

 

Forty studies involving 867 patients (including the present series) met the inclusion criteria and were included for review.^[17-55] An overview of these studies is shown in Table. All these studies were observational. The sample size of each study varied from 5 to 100 patients. The overall pancreatic fistula rate of the patients was 33.4% (0-100%). Of them, 89.6% (250/279) had grade A or B fistulae of ISGPF, all of which were managed successfully non-operatively; 10.4% (29/279) had grade C fistulae of ISGPF. The re-operative rate in all patients was 7.7% (15/194). Only one patient with grade C fistula of ISGPF died several days after re-operation from multiple organ failure, resulting in an overall mortality rate of 0.3% (1/290).

 

The source of fistula was identified in only 19 patients: 7 from the proximal remnant and 12 from the distal pancreatic anastomosis.^{[17, 20, 23, 30, 31, 52]} All 7 fistulae originating from the proximal remnant were grade A or B fistulae of ISGPF. In contrast, 5 of 12 leakages from the distal pancreatic anastomosis were due to grade C fistulae of ISGPF, and were treated by re-operation. One patient subsequently died from multiple organ failure.

 

 

Traditionally, enucleation or formal pancreatectomy is the treatment of choice for benign or borderline lesions of the neck and body of the pancreas. However, enucleation is not always applicable because of the lesion size and location. Besides, this surgical procedure runs a high risk of injury to the main pancreatic duct. Formal pancreatectomy, including pancreatoduodenectomy (PD) and distal pancreatectomy, may sacrifice the normal pancreatic parenchyma and can be associated with the risk of postoperative diabetes mellitus, exocrine and endocrine pancreatic insufficiency. CP represents an organ-preserving operation. This modality has the advantages of preserving the integrity of the gastrointestinal tract and splenic function, and sparing the maximal pancreatic endocrine and exocrine function by avoiding extended resection of the pancreas.^[17-20]

 

However, these benefits may be outweighed by the greater pancreatic fistula rate associated with CP. The overall pancreatic fistula rate was 33.4% in the current collective review of 867 patients who underwent CP. It was reported that the fistula rate after CP was significantly higher than that after PD or distal pancreatectomy,^[1-15] because there are two transected pancreatic surfaces in CP, thus potentially facilitating the formation of pancreatic fistula. On the other hand, indications for CP are generally limited to benign or low-grade malignant neoplasms. The soft remnant pancreas and the small main pancreatic duct become established risk factors associated with the development of pancreatic fistula.^[56]

 

According to the ISGPF definition, grade A or B fistulae can be managed successfully by conservative measures or mini-invasive approaches, while grade C fistulae may induce life-threatening complications and often requires re-operation for definitive management.^[16] Despite the relatively high occurrence of postoperative pancreatic fistula in our patients, most pancreatic fistulae after CP were grade A or B fistulae of ISGPF, and only 10.4% were grade C fistulae. This figure is lower than that of PD. A recent systematic review of 2706 PD cases reported that grade C pancreatic fistula accounted for 15% of all their 479 cases of pancreatic fistulae.^[57] Pratt,^[29] Hirono,^[41] DiNorcia,^[46] Xiang^[55] and their colleagues consistently demonstrated that the occurrence of grade C fistulae of ISGPF with CP was similar to that with distal pancreatectomy. These data indicate that CP does not seem to increase the severity of fistula.

 

According to literature review, the leakage from the distal pancreatic anastomosis is likely to cause more severe clinical consequences. Recently, an Italian group described inframesocolic pancreatojejunostomy after CP, where the cut end of the distal pancreatic stump after CP was brought in the inframesocolic compartment through a small transverse mesocolic window.^[52] Pancreatojejunostomy was hence constructed in the intraperitoneal compartment, being divided by the retroperitoneal proximal pancreatic stump by the transverse mesocolon itself. Segregation of the two pancreatic stumps into different body compartments allows for selective identification of the source of a fistula.

 

Pancreaticojejunostomy and pancreaticogastrostomy are two commonly preferred methods for reconstruction of the distal pancreatic remnant. Sauvanet et al^[23] and Brown et al^[30] groups found that both techniques had an equivalent fistula rate in CP. Xiang et al^[55] reported that pancreaticogastrostomy for the distal pancreatic remnant reduced the occurrence of pancreatic fistula, whereas Venara et al^[54] showed a lower anastomotic leakage rate with pancreaticojejunostomy. Therefore, controversies still exist over ideal distal pancreatic anastomosis. Wayne et al^[43] reported that there was no pancreatic leakage in a series of 10 patients who underwent CP without pancreatico-enteric anastomosis. However, their conclusion needs to be confirmed by further studies of other centers.

 

Indications for CP include various benign and borderline tumors (neuroendocrine, serous and mucinous cystadenomas, non-invasive intraductal mucinous producing tumors, solid pseudopapillary tumors) and chronic pancreatitis with segmental stenosis of Wirsung's duct.^[51] The technique is contraindicated for malignant lesions owing to limited oncological radicality. In case of invasive malignancy as confirmed by intraoperative histopathological examinations, the operation should be extended as a proximal or distal pancreatic resection.

 

In conclusion, despite the relatively high occurrence of pancreatic fistula after CP, most cases were grade A or B fistulae of ISGPF that can be managed successfully by conservative measures or mini-invasive approaches. It appears that fistulae originating from distal pancreatic anastomosis have poorer clinical consequences as compared with those originating from the proximal remnant. A recent meta-analysis showed that external pancreatic duct stenting could reduce the occurrence and severity of pancreatic fistula after pancreatic resection.^[58] This technical modification has the advantages of diverting away pancreatic juice from the anastomosis and preventing activation of pancreatic enzymes by enterokinase in the small bowel mucosa soon after surgery. In a prospective randomized trial involving 158 patients with a high risk of fistula (soft pancreas and a non-dilated pancreatic duct), Pessaux et al^[56] found that external pancreatic duct stenting decreased the pancreatic fistula rate after PD, because the pancreas is soft and the main pancreatic duct is non-dilated in most cases of CP. It is expected that external drainage of the pancreatic duct may be particularly helpful in reducing the occurrence of pancreatic fistula in patients undergoing CP, though it needs verification in further study.

 

 

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