Delayed postpancreatectomy hemorrhage as the role of endovascular approach: Four case reports

Abstract

BACKGROUND

Pancreatic resection is still associated with high morbidity rates and delayed postpancreatectomy hemorrhage (PPH) is the most feared complication as it may lead to hemorrhagic shock or serious septic complications. Today, endovascular approach represent safe and efficient method for minimally invasive management of extraluminal PPH.

CASE SUMMARY

We describe four patients whose postoperative recovery after pancreatic resection was complicated by postoperative pancreatic fistula (POPF) and visceral artery hemorrhage. In all cases endovascular approach was utilized and it resulted in satisfactory outcomes. We discuss modern diagnostic and therapeutic approach in this clinical scenario.

CONCLUSION

PPH is relatively uncommon, but it is a leading cause of surgical mortality after pancreatic surgery. Careful monitoring and meticulous follow-up are required for all patients post-operatively, especially in the case of confirmed POPF, which is the most significant risk factor for the development of a PPH. Angiography as a diagnostic and therapeutic method may be an optimal first-line treatment for the management of delayed PPHs. In our experience, endovascular treatment for hemorrhagic complications of pancreatic resections has shown satisfactory results.

Key Words: Pancreas; Resection; Hemorrhage; Angiography; Embolization; Surgery; Case report

Core Tip: Pancreatic resections are associated with specific complications and most feared one is hemorrhage due to erosion of large peripancreatic vessels. It is rare, but serious clinical scenario which should be considered in all cases of postoperative hemodynamic instability or pulsating pain even in late postoperative phase. Nowadays, embolization may be therapeutic option for many cases of postpancreatectomy hemorrhage and it provides quick hemostasis with minimal invasiveness. Surgery is reserved for massive uncontrollable hemorrhage or when embolization fails.

INTRODUCTION

Pancreatic resection is a complex procedure, and despite recent advances in techniques and perioperative care, it is still associated with a high complication rate. The most common complications are intra-abdominal infections and pancreatic fistulas. Postpancreatectomy hemorrhage (PPH) is relatively rare (incidence between 2% and 8%), but it represents a life-threatening complication associated with a high mortality rate[1]. To overcome confusion regarding the definition of PPH, in 2007, an international study group on pancreatic surgery suggested standardization of the definition and proposed how PPH should be characterized[2]. The recommendations propose that PPH should be categorized based on three specific criteria: (1) Time of onset; (2) Location and cause; and (3) severity of bleeding. Regarding time of onset, PPH was divided into early (occurring during the first 24 hours postoperatively) and delayed (occurring 24 and more hours postoperatively). This distinction is important since each type of PPH has specific causes and treatment approaches. Early PPH (E-PPH) is seen in the first 24 hours postoperatively, and it is caused by a technical failure of appropriate hemostasis or an underlying perioperative coagulopathy. Initial treatment includes blood transfusions and coagulopathy management, and in cases of failure, surgical exploration and hemostasis are required. Conversely, delayed PPH (D-PPH) occurs later, > 24 hours after the surgery and, in many cases, several days or even weeks after it. D-PPH is caused by specific surgical complications such as intraabdominal infections, erosion of peripancreatic vessels as a result of fistulas or abdominal drains, anastomotic hemorrhage, or rupture of arterial pseudoaneurysms (PSAN).

Location of bleeding is either intraluminal or extraluminal, while its severity can range from mild to severe, depending on factors such as volume of blood loss, clinical impairment, and the need for surgical reintervention or interventional angiographic embolization. In addition, the clinical grading system of PPH with grades A, B and C was proposed: PPH grade A has no major impact on standard postoperative care, and length of hospital stay, while PPH grade B always requires further diagnostics and will lead to therapeutic consequences such as the need for blood transfusion or the need for reintervention. PPH grade C refers to life-threatening bleeding requiring immediate diagnostics and therapy and it invariably leads to an extended hospitalization period and frequently requires admission to intensive care units (ICU).

PPH can manifest in several clinical presentations, and depending on its location, it can be intraluminal or extraluminal[3]. Intraluminal PPH is defined as the occurrence of blood draining via the nasogastric tube, hematemesis, or melena, while extraluminal PPH is characterized by the presence of blood in abdominal drains or when hematoperitoneum is detected intraabdominally via radiologic tests. Sentinel bleed is specific category of bleeding defined as minor blood loss via surgical drains or the gastrointestinal tract. It is generally asymptomatic, but its significance lies in the fact that after asymptomatic interval, hemorrhagic shock may develop, therefore sentinel bleed may be alert for potentially more serious bleeding from PSAN or vascular erosions[4].

Diagnostic and treatment options include early computed tomography (CT) with angiography, upper gastrointestinal endoscopy, interventional angiography and relaparotomy[5]. Diagnostic angiography including digital subtraction angiography (DSA) may localize the bleeding site, and thereafter an embolization can be performed. When it is not technically feasible or when massive bleeding is present, a surgical re-exploration may be needed. Surgery is also indicated when it is necessary to treat a concomitant complication (e.g. pancreatic fistula or intraabdominal abscess). Endoscopy may be useful in the treatment of intraluminal bleeding.

In this article, we report four patients whose postoperative recovery after pancreatic resection was complicated by postoperative pancreatic fistula (POPF) and visceral artery hemorrhage (Table 1). Two patients underwent distal pancreatectomy, one underwent pancreaticoduodenectomy (Whipple procedure), and another underwent the excision of an insulinoma. All patients experienced late PPH, a serious complication requiring prompt diagnosis and treatment, most commonly in the form of endovascular visceral artery embolization. Satisfactory resolution after endovascular treatment was achieved in all four cases.

Table 1 Clinical and treatment characteristics of patients.

Patient/Sex/Age	Diagnosis	Operation	Bleeding POD	Bleeding location	PSAN	PSAN size	Pancreatic fistula	Fistula grade	Bleeding presentation	Treatment
Case 1/F/52	Insulinoma	Insulinoma enucleation	7	GDA	-	-	+	B	Hypotension and febrile state	Endovascular GDA embolization, relaparotomy
Case 2/M/46	Chronic pancreatitis	Pancreato-duodenectomy	16	GDA	+	7 mm	+	B	Abdominal pain, drainage tube hemorrhage	Relaparotomy, endovascular GDA embolization
Case 3/M/82	Neuroendocrine tumor	Spleen preserving pancreatectomy	57	SA	+	14 mm	+	B	Hematemesis, abdominal pain	Endovascular SA embolization, CT guided drainage
Case 4/F/62	Insulinoma	Pancreato-duodenectomy (Whipple)	43	SA	+	18 mm	+	B	Hematemesis	Endovascular SA embolization

F: Female; M: Male; POD: Postoperative day; GDA: Gastroduodenal artery; SA: Splenic artery; PSAN: Pseudoaneurysms; CT: Computed tomography.

CASE PRESENTATION

Chief complaints

Case 1: A 52-year-old woman complained of hypoglycemia (blood glucose level of < 2.0 mmol/L), persistent nausea, and blurred vision for 4 weeks.

Case 2: A 46-year-old man presented with recurrent episodes of pancreatitis, most likely caused by pancreas divisium, which was confirmed through endoscopic retrograde cholangiopancreatography (ERCP).

Case 3: An 82-year-old man had routine ultrasound check up that discovered pancreatic nodule located in the pancreatic tail.

Case 4: A 62-year-old female presented with episodes of hypoglycemia and flushing for 4 months.

History of present illness

Case 1: The patient developed refracted hypoglycemia and generalized weakness that progressed over 4 weeks. She had no specific abdominal symptoms.

Case 2: The patient experienced intermittent colicky pain in the upper abdomen associated with nausea and weight loss over the 6 months period.

Case 3: The patient was asymptomatic.

Case 4: The patient visited general practitioner for evaluation of flushing and hypoglycemia. She experienced these symptoms for 4 months.

History of past illness

Case 1: She had previous history of arterial hypertension and hypothyroidism.

Case 2: No significant past history or any illness or surgery.

Case 3: He had cholecystectomy 4 years ago and chronic renal insufficiency.

Case 4: She had uterine fibroids and arterial hypertension.

Physical examination

Case 1: Physical examination showed no specific abnormalities.

Case 2: Physical examination showed slightly tender upper abdomen.

Case 3: The physical examination was normal.

Case 4: The patient was obese, but had no specific abdominal pain.

Laboratory examinations

Case 1: Laboratory test results upon admission were as follows: White blood cell count: 12.14 × 10⁹/L (3.5-9.5 × 10⁹/L); Hematocrit: 43% (40%-50%); C-reactive protein: 24 mg/L (0-8 mg/L); Serum amylase: 98 U/L (25-125 U/L); Serum lipase: 158 U/L (20-180 U/L); Serum calcium: 1.98 mmol/L (2.25-2.75 mmol/L); Alanine aminotransferase: 212 U/L (0-40 U/L); Aspartate aminotransferase: 54 U/L (0-40 U/L); Blood glucose level: 1.7 mmol/L (3.9-5.6 mmol/L).

Case 2: Blood test results were as follows: White blood cell count: 9.14 × 10⁹/L (3.5-9.5 × 10⁹/L); Hematocrit: 48% (40%-50%); C-reactive protein: 8 mg/L (0-8 mg/L); Serum amylase: 145 U/L (25-125 U/L); Serum lipase: 225 U/L (20-180 U/L); Blood glucose level: 6.7 mmol/L (3.9-5.6 mmol/L).

Case 3: No abnormal laboratory findings were noted.

Case 4: Pathological blood test was as follows: White blood cell count: 16.14 × 10⁹/L (3.5-9.5 × 10⁹/L); C-reactive protein: 48 mg/L (0-8 mg/L); Serum amylase: 171 U/L (25-125 U/L).

Imaging examinations

Case 1: CT scan showed 3 cm tumor nodule located within the neck of the pancreas.

Case 2: ERCP revealed pancreas divisum and mild chronic pancreatitis and obstruction of intrapancreatic common bile duct.

Case 3: CT showed a 4 cm neuroendocrine tumor located in the pancreatic tail.

Case 4: The neuroendocrine tumor was confirmed via selective angiography of the gastroduodenal artery (GDA) and it was located in the pancreatic tail.

FINAL DIAGNOSIS

Case 1

The diagnosis of pancreatic neck insulinoma was established.

Case 2

Common bile duct obstruction and pancreas divisum were initial diagnosis.

Case 3

The patient was diagnosed with pancreatic tail insulinoma.

Case 4

Findings suggested the neuroendocrine tumor located in the pancreatic tail.

TREATMENT

Case 1

The patient underwent pancreatic tumor enucleation via open approach. No intraoperative difficulties were encountered. Macroscopically free tumor margins were achieved. The surgical procedure was uneventful. On postoperative day (POD) 7, the patient became febrile, so a CT was done, which showed a fluid collection at the resection site, indicating a possible pancreatic fistula (Figure 1A). Drainage of the collection under CT guidance was performed. Analysis of the drained fluid revealed an elevated concentration of alpha-amylase (56180 U/L), thus confirming the presence of a pancreatic fistula. Five days later, the patient became hypotensive and febrile, prompting a new CT scan. The previously described fluid collection had expanded, exhibiting features suggestive of hematoma, thereby raising concerns about a potential hemorrhage originating from the GDA.

Figure 1 Computed tomography. A: Abdominal computed tomography scan showing a fluid collection at the resection site (orange arrow); B: Computed tomography identified a large collection of dense fluid at the resection site (orange arrow); C: Abdominal computed tomography scan showing 14 mm visceral arterial pseudoaneurysm of the splenic artery (arrow).

To address this concern, DSA was conducted, followed by embolization of the GDA with endovascular coils using the “front-back door” method (Figure 2A and B). The procedure was uneventful. Despite clinical and laboratory signs of adequate hemostasis, the patient had signs of progressive sepsis, so 12 hours after the radiological intervention, a relaparotomy was performed that revealed a significant accumulation of hematoma around the enucleated part of the pancreas. Additionally, pancreatic head inflammation with areas of caseous necrosis was identified, indicative of acute pancreatitis. The hematoma was evacuated, and four abdominal drainage tubes were placed, two on each side of the abdomen.

Figure 2 Digital subtraction angiography. A: Digital subtraction angiography shows extravasation of the intravenous contrast from the gastroduodenal artery (arrow); B: Successful obliteration of the gastroduodenal artery stump with endovascular coiling; C: 7 mm visceral arterial pseudoaneurysm of the gastroduodenal artery stump (arrow); D: Successful embolization of the gastroduodenal artery pseudoaneurysm using endovascular coiling; E: Visceral arterial pseudoaneurysm of the splenic artery (arrow); F: Successful obliteration of the splenic artery using endovascular coils; G: Digital subtraction angiography shows 18 mm visceral arterial pseudoaneurysm of the splenic artery (arrow); H: Successful obliteration of the splenic artery using endovascular co.

Case 2

The patient underwent cephalic pancreatoduodenectomy with pancreatico-jejunal anastomosis. During the first post-operative week, the patient was recovering well. He was afebrile, hemodynamically stable, and his abdominal drain was removed. On the POD 8, the patient complained of severe abdominal pain. CT identified a large collection of dense fluid at the resection site, as well as pneumoperitoneum (Figure 1B). Additionally, bilateral pleural effusion was noted, leading to minor respiratory distress.

Upon relaparotomy, a large amount of inflamed hematoma and fresh blood were found in the right abdominal and pelvic area. Hematoma was evacuated, peritoneal lavage was performed, and 4 abdominal drainage tubes were placed to drain subhepatic space, omental bursa and pelvis. The patient’s post-operative course was further complicated by the development of a grade B POPF. Conservative treatment of the fistula was initiated and the patient was discharged on POD 11 in good condition, with the one remaining drain left as there was persistent moderate fistula output. Five days later, the patient returned to the emergency room due to sudden bloody secretion from the abdominal drainage tube. An urgent abdominal CT was performed, revealing a potential PSAN of the GDA stump. The PSAN was confirmed via DSA, followed by successful endovascular coil embolization of the GDA stump (Figure 2C and D).

Case 3

Surgery was indicated and it included spleen-preserving distal pancreatectomy and cholecystectomy. The procedure and postoperative recovery were uneventful and the patient was discharged on the POD 16. Two months later, on the POD 57, the patient was readmitted to the emergency department due to episodes of hematemesis occurring 3 to 4 times within the previous 24 hours and accompanied by upper abdominal pain. Physical examination revealed a soft abdomen with lower quadrant tenderness on palpation. Emergency CT identified two heterogeneous masses, one of which was connected to the splenic artery (SA), thus confirming the diagnosis of a PSAN of the SA (Figure 1C).

The patient underwent endovascular embolization of the splenic PSAN with 11 coils, which successfully managed the bleeding (Figure 2E and F). The second heterogeneous mass, a hematoma, was drained using the Seldinger technique. The splenic abscess and pleural effusions were treated conservatively.

Case 4

The patient underwent standard cephalic pancreaticoduodenectomy. On the POD 2, the patient became febrile. An emergent abdominal CT revealed two fluid collections, which were then drained percutaneously, and the drained content was sent for microbiological analysis. The patient’s antibiotic therapy was corrected, which led to a reduction in inflammatory markers. On the POD 29 the patient was discharged in good condition. After 14 days, on POD 43, the patient presented to the emergency department with hematemesis. She was also persistently hypoglycemic. An abdominal CT scan with contrast revealed new areas of extravasation during the arterial phase, confirming the presence of a PSAN of the SA. The patient underwent endovascular embolization of the SA-PSAN, which included the application of 10 coils (Figure 2G and H). After the procedure, the patient’s blood glucose levels were normalized.

OUTCOME AND FOLLOW-UP

Case 1

No additional complications were seen, and the patient was discharged on POD 18. The two remaining abdominal drains were removed two months later. At one-year follow-up, the patient was asymptomatic and showed no evidence of pancreatic insufficiency.

Case 2

Subsequently, the abdominal drain was safely removed after 2 weeks, and the patient was discharged 3 days later. At 2-years follow-up no complaints were reported by the patient.

Case 3

The patient was discharged on the 24^th day after admission in stable general condition. At 1-year follow up the patient was asymptomatic.

Case 4

The patient was discharged 14 days later, euglycemic, and with the recommendation of meticulous follow-up with an endocrinologist, due to reduced perfusion of the remaining pancreatic tissue following SA embolization. At 1-year follow-up the patient was good and no signs of glycemic disorders were found.

DISCUSSION

Delayed gastric emptying, pancreaticojejunal anastomotic failure, and intra-abdominal abscess are predominant causes of morbidity after pancreatectomies. PPH is reported less frequently, but it has significantly higher mortality rates (a mortality rate between 30 and 50%) as compared to other complications, with the principal cause of death being overwhelming sepsis rather than uncontrolled bleeding[6]. Therefore, beside prompt hemostasis, the important role in management is sepsis control through adequate intraabdominal drainage of intraabdominal collections and appropriate antibiotic therapy. Delayed hemorrhage is most commonly associated with PSAN rupture and inflammatory erosion of the arterial wall. Although, there is no established consensus on the exact pathophysiology of PSAN creation after pancreatic resection, there is a clear association with a previously formed POPF[7,8]. Therefore, erosion of blood vessels due to postoperative leakage of a pancreatic or biliary anastomosis is recognized as the most significant cause of postoperative PSAN formation. Subsequent intra-abdominal abscesses may further erode vessels. There is also a possibility that the placement of drainage tubes may cause mechanical pressure on the vessel or facilitate the spreading of infection.

Unlike in E-PPH, in D-PPH, the treatment decision making process is often challenging. and the treatment remains controversial since there is no uniformly accepted algorithm. Historically, urgent surgical exploration was the only justified intervention, but the development of endovascular methods changed the paradigm in the treatment of D-PPH since it caused a shift toward the use of angiography with embolization[4,5,9,10]. Angiography may easily localize the bleeding site, and embolization can be immediately performed. Therefore, when newly formed visceral PSAN are the source of bleeding, which, according to 2008 meta-analysis[11], happens in approximately one third of PPH cases, endovascular embolization should be considered as the first line of treatment[11,12].

Endovascular approach is even more justified as time after surgery passes since it has been shown that over time the probability of anastomotic bleeding decreases and that of visceral arterial bleeding increases. Main advantages of the endovascular approach is minimal invasiveness and the fact that it avoids damage to other organs. In addition, surgical procedure is associated with high risk of complications and often it ends with completion pancreatectomy. Modified anatomy, postoperative adhesions, and inflammatory peripancreatic changes compromise the safety of the surgical approach[13]. Therefore, in D-PPH when there is no massive bleeding associated with hemodynamic instability, every effort should be made to avoid surgery. Angiography may be both diagnostic and therapeutic, and even if there is no complete success, it may delay the need for urgent surgery.

Given the danger of PPH, many authors investigated possible intraoperative or postoperative strategies for the prevention of PPH[14]. Possible beneficial intraoperative measures include pancreatic anastomosis with a small jejunal incision, falciform ligament wrap around the GDA stump, and pancreaticojejunostomy (vs pancreaticogastrostomy). Postoperative measures include somatostatin analogues administration, and algorithm-based postoperative patient management, but the effects of these still require clinical and scientific evaluation. Additionally, surgeons should suture-ligate and dissect the GDA as far away from the common hepatic artery as possible to create sufficient space for potential embolization. However, in some cases, angiography may not be appropriate, mostly when bleeding is intermittent, venous, or diffuse.

Study from Floortje van Oosten et al[15] showed that the mortality rate was lower after a primary endovascular approach as compared to primary relaparotomy (15% vs 37%), but we should keep on mind that a possible explanation for the difference in mortality rates between the interventional strategies, might lie in their respective indications.

In 2016, international study group of pancreatic surgery published a revised classification and grading system for POPF. The new term proposed for what was formerly grade A POPF is biochemical leak, and it is no longer considered a true pancreatic fistula or an actual surgical complication[16]. A biochemical leak, by definition, has no clinical impact. It implies no deviation from the normal postoperative pathway and does not result in a prolonged hospital stay. Grade B and C POPF remain clinically relevant, defined as a drain output of any measurable volume of fluid with an amylase level greater than three times the upper institutional normal serum amylase level, and associated with a clinically relevant development/condition related directly to the POPF. Grade B refers to a properly defined fistula that always changes the usual postoperative course. Once single or multiple organ dysfunction occurs, or the patient needs reoperation, the fistula shifts to grade C. With grade C POPF, stay in the ICU is often required, and hospital stay is always prolonged.

The most commonly reported origin of PPH is the stump of the GDA. However, as reported by Ielpo et al[17], the artery involved is usually related to a specific pathology. For example, splenic PSANs are most commonly associated with pancreatitis and extended pancreatic resection, while hepatic artery PSAN is usually iatrogenic after liver resection or transplantation[18]. Lee et al[19] report PSAN of the GDA, common hepatic artery, proper hepatic artery, and the left hepatic artery as the most commonly occurring locations after pancreatoduodenectomy. In our case series, we encountered two PSAN of the GDA stump, and two SA-PSAN, one of which occurred alongside a left hepatic artery PSAN. All of these complications presented after pancreatic resection.

Patients we present in this case series developed POPFs during the early days of recovery. The presence of pancreatic fistulas was suspected due to increased postoperative drain output, and confirmed via laboratory analysis of the drained fluid, which revealed a more than 3 times greater value of alpha-amylase than the normal serum concentration. All of the patients experienced late grade B PPH. The onset of bleeding ranged from POD 7 to POD 57. Massive arterial bleeding can occur late in the postoperative period. Lee et al[19] reported a median period of 21 days for pseudoaneurysmal bleeding to occur after pancreatic resections. In the same study, in several cases, bleeding was seen beyond 4 weeks postoperatively. This should prompt surgeons to give precise instructions on at-home drain output monitoring post-discharge and provide diligent follow-up examination.

Depending on the location of the PSAN, the subsequent hemorrhage will present either as extraluminal or intraluminal. Extraluminal bleeding is a result of PSAN rupture directly into the abdominal cavity, while intraluminal ones occur when the PSAN is attached to the gastrointestinal tract and it rupture into the lumen. Out of the four patients we described, two had extraluminal, and two experienced intraluminal gastrointestinal hemorrhage. This is an important distinction, because it greatly affects the patient’s presentation. Both of the patients with intraluminal hemorrhage presented with hematemesis, while extraluminal hemorrhage resulted in hypotensive shock in one and sudden sanguinous drain output accompanied by severe abdominal pain in the other patient. Upon the presentation of postoperative hemorrhages, all patients underwent emergency CT scans. Two patients that presented with extraluminal bleeding both underwent DSA and simultaneous embolization via endovascular coiling, even though one of the patients previously underwent a relaparotomy with the intent of hematoma removal, followed by an abdominal lavage. A recent meta-analysis of non-randomized studies comparing endovascular management and laparotomy for delayed massive hemorrhage suggested lower complication and mortality rates in the endovascular group[20]. In both cases of intraluminal bleeding, our patients underwent endovascular embolization. Iswanto and Nussbaum[21] suggested that angiographic embolization should be performed proximal and distal to the origin of the PSAN rather than proceeding with embolization in the pseudoaneurysmal cavity to avoid wall rupture and persistent bleeding/recurrence of bleeding, and same principles were used in our patients.

CONCLUSION

PPH is relatively uncommon, but it is a leading cause of surgical mortality after pancreatic surgery. Careful monitoring and meticulous follow-up are required for all patients post-operatively, especially in the case of confirmed POPF, which is the most significant risk factor for the development of a PPH. Angiography as a diagnostic and therapeutic method may be an optimal first-line treatment for the management of delayed PPHs. In our experience, endovascular treatment for hemorrhagic complications of pancreatic resections has shown satisfactory results.