Keywords

Introduction

The mortality rate after pancreaticoduodenectomy (PD) has decreased markedly over the last several decades. However, the morbidity rate has not decreased to the same extent; complications continue to occur in 30–40 % of patients who undergo pancreatectomy (PD or distal pancreatectomy) [1, 2]. Postpancreatectomy hemorrhage (PPH) is one of the major causes of morbidity and can result in mortality after PD or distal pancreatectomy [3, 4]. In particular, late PPH is associated with a high mortality rate because the diagnosis may not be apparent, the patient may no longer be an inpatient and the hemorrhage may present as abrupt, massive bleeding [5, 6].

PPH occurs between 1 and 8 % of all pancreatic resections and accounts for 11–38 % of overall mortality [3, 7–9]. This wide variation is caused by different definitions used by authors in the reporting of results. The International Study Group of Pancreatic Surgery has clinically graded PPH based on onset, location, and severity [10]. Generally, PPH can be divided into early and late postoperative bleeding. Early PPH is that which occurs within 24 h of surgery. It often is caused by technical failure to achieve appropriate hemostasis during the index operation or an underlying perioperative coagulopathy. Late PPH occurs more than 24 h after the operation, and usually after 7–10 postoperative days. Late PPH typically results from complications of the operation and becomes clinically apparent several days or even weeks after surgery. For example, late PPH may occur following the diagnosis of an intra-abdominal abscess, erosion of a peripancreatic vessel secondary to a pancreatic fistula or an intra-abdominal drain, ulceration at the site of an anastomosis, or in association with an arterial pseudoaneurysm. Late PPH or delayed bleeding is one of the most feared postoperative complications because it is often not accurately diagnosed and therefore not treated effectively. Late PPH under these circumstances is associated with a high mortality rate because of the already poor condition of the patient [11].

PPH may originate from arterial or venous vessels, suture lines, areas of resection (pancreatic stump, retroperitoneum), gastric/duodenal ulcer or diffuse gastritis, eroded and ruptured pseudoaneurysms, or hemobilia from previously placed endobiliary stents [10] (Table 26.1). Vascular structures that may be the source of PPH include the stump of the gastroduodenal artery (GDA; most common and well known cause of late PPH), splenic artery, branches of the superior mesenteric artery (SMA) (e.g., inferior pancreaticoduodenal artery especially in the setting of a clinically significant pancreatic anastomotic leak), the splenic vein stump, or, rarely, an intrapancreatic artery. In addition, PPH can be grouped into intraluminal and extraluminal; intraluminal PPH manifests itself as hematemesis, bleeding from the nasogastric tube, or melena, and extraluminal PPH is characterized by bleeding from intra-abdominal drains, an abdominal wound, or intra-abdominal hemorrhage. True extraluminal bleeding has an extraluminal source. False extraluminal bleeding is a manifestation of primary intraluminal bleeding that becomes extraluminal owing to coexisting anastomotic disruption [12–14].

Table 26.1 Location, onset, diagnosis, and management of postpancreatectomy hemorrhage (PPH)
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Early PPH (within 24 h after surgery) is most commonly the result of technical failure to properly secure the inferior pancreaticoduodenal arteries (IPDAs). One can also see bleeding at any of the three anastomotic suture lines (following PD) and rarely a GDA stump hemorrhage due to failure to properly secure this vessel. If the SMA dissection is performed sharply with direct identification and ligation of the IPDAs at their origin from the SMA, this complication can largely be avoided. Intra-abdominal hemorrhage from poorly secured IPDAs would present as early postoperative intra-abdominal hemorrhage and would require immediate reoperation. Bleeding from the post-PD reconstruction (pancreatic, biliary, or gastric anastomosis) is very uncommon, and the anastomosis of greatest risk is the pancreaticojejunostomy if an invagination anastomosis is performed. With this type of anastomosis, the cut surface of the pancreas is open to the inside of the jejunum and small vessels which are partially cauterized may retract at the time of pancreatic transection only to bleed when the patient is in the recovery room or during the first postoperative night. Hemorrhage from the biliary anastomosis should not occur, and bleeding from the gastrojejunostomy is also very uncommon in the absence of a technical error. Marginal ulceration at the gastrojejunostomy, if it were to occur, presents months or years after the date of surgery. Yekebas et al. presented an analysis of 1669 consecutive pancreatic resections and in their experience, early PPH was due to 3 causes: (1) technical failures in terms of inadequate hemostasis in the operative field always associated with extraluminal PPH (IPDAs being the most common involved vessels); (2) suture line of gastroenteric or one of the enteroenteric anastomoses leading uniformly to intraluminal PPH on the first or second postoperative day; and (3) resection cavity or transection surface of the pancreas resulting in PPH originating from the pancreatico-enteric anastomosis [15].

Late PPH may occur from a gastrointestinal source but more commonly originates from an intra-abdominal site often associated with intra-abdominal infection or abscess formation due to leakage of an anastomosis (most commonly the pancreaticojejunostomy). Intra-abdominal infection is thought to be the major cause of late PPH due to erosion into ligated vessels, most notably the GDA. Bleeding from a disrupted anastomotic suture line can also be caused by intra-abdominal infection and can mimic bleeding from major vessels [7, 8, 16]. Finally, some patients may present with bleeding from the wound after a wound infection but significant hemorrhage from this etiology is uncommon.

The core difference between the etiology of early and late PPH is the association of late PPH with pancreatic fistula and intra-abdominal infection. This finding is consistent throughout the surgical literature which notes an elevated risk of late PPH in patients with pancreatic fistula as well as a near 100 % prevalence of pancreatic fistula in patients who exhibit late arterial bleeding [16, 17]. Surgical reports are consistent in describing a sequence of events at the beginning of which pancreatic fistula causes erosions, pseudoaneurysms, and other vascular irregularities, which eventually result in clinically significant hemorrhage. Clearly, the majority of postoperative pancreatic fistulas do not result in late PPH and the cause of PPH within the population of patients who have a pancreatic leak is likely multifactorial. Extended lymphadenectomy or the need for concomitant adjacent organ resection (resulting in a large retroperitoneal space), soft texture of the pancreatic remnant in the setting of a complete anastomotic disruption, or insufficient drainage of pancreatic fistula (failure to obtain source control) may be the cofactors increasing the risk of fistula-induced vascular injury and PPH [16–18].

Possible pathophysiologic explanations for pancreatic anastomotic leak-associated late PPH include enzymatic digestion of the blood vessel wall by trypsin, elastase, and other pancreatic exocrine enzymes, intra-abdominal infection/abscess with direct involvement of the vessel wall, and/or vascular injury at the time of operation that leads to pseudoaneurysm formation [3]. Most reports and anecdotal clinical observations favor the theory of local sepsis resulting from pancreatic fistula as the main cause of late PPH. Local sepsis may erode the vascular wall and adjacent bowel. This mechanism of injury may result in acute arterial bleeding with or without arterial pseudoaneurysm formation, which typically occurs days to weeks after the operation [19]. There is minimal data regarding the impact of newer energy devices, especially when using them for ligating the IPDAs arising from the SMA; however, anecdotal experiences with such situations have generated reason for caution. Many of us have managed PPH in patients where the use of such energy devices close to arterial structures has been implicated in the etiology of late PPH.

Skeletonization of the hepatic artery and SMA which is performed with PD, and similar dissection of the celiac artery and splenic artery stump associated with distal pancreatectomy make these vessels vulnerable to pseudoaneurysm formation due to local sepsis arising from the pancreatic fistula, anastomotic leakage, or intra-abdominal abscess [20]. In a series reported by Lee et al., of 27 patients with PPH, 26 had an antecedent pancreatic fistula, as shown by drain amylase level and computed tomography (CT) findings. This report confirms the association between late PPH and pancreatic fistula. The onset of the infectious complication ranged from 7 to 13 days but the hemorrhage developed after postoperative day 28 in 9 patients. The high frequency of late-onset (after 4 weeks from the date of operation) hemorrhage in this study led the authors to conclude that PPH can occur more than 4 weeks postoperatively, particularly in patients with pancreatic fistula and/or a complicated initial postoperative course [21].

Prevention of Late PPH

The Falciform Ligament

When opening the abdomen, we carefully preserve the falciform ligament (obliterated umbilical vein) for later use as coverage of the GDA stump, vascular anastomoses, or other peripancreatic vessels [22]. A pedicled falciform ligament is easily and rapidly obtained during a midline abdominal incision. After incising the linea alba, the preperitoneal fat is dissected laterally (to the left) when incising the peritoneum. The falciform ligament is mobilized by dividing it near the umbilicus and incising its anterior peritoneal reflections along the posterior rectus sheath. An additional length is obtained by continuing the anterior incision cephalad to the anterior surface of the liver. The pedicled falciform ligament is completed by taking down the attachments of the liver until just the obliterated umbilical vein remains attached. Note that the pedicled falciform ligament (Fig. 26.1) normally reaches the space between the pancreaticojejunostomy and the major vessels exposed during resection. After completion of the pancreatectomy, the pedicled falciform ligament is spread widely anterior to the common/proper hepatic artery with special attention to coverage of the GDA stump. A robust flap usually also covers the superior mesenteric vein (SMV), portal vein (PV), and splenic vein confluence effectively separating the vessels from the afferent jejunal limb (Fig. 26.2). When a distal pancreatectomy is performed, the pedicled falciform ligament can be fixed with 4-0 prolene sutures to the remnant pancreas thereby reinforcing the pancreatic closure. This procedure enables the complete separation of these vessels from the pancreas in the event that a pancreatic fistula and associated abscess were to develop.

Fig. 26.1
figure 1

Intraoperative photograph of preserved falciform ligament pedicle flap. Debakey forceps are retracting the liver. White arrows point to the falciform flap

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Fig. 26.2
figure 2

Intraoperative photograph of completed pancreaticoduodenectomy. The falciform ligament pedicle flap ( white arrows) completely covers the common hepatic artery and GDA stump from any possible PJ leak. HJ hepaticojejunostomy, PJ pancreaticojejunostomy, SMV superior mesenteric vein, SV splenic vein

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The Portal Dissection

The portal dissection is initiated by removing the lymph node that lies directly anterior to the common hepatic artery (CHA) proximal to the right gastric artery and GDA. This facilitates exposure of the CHA proximal and distal to the GDA. The right gastric artery is ligated and divided followed by the GDA. Dissection of the hepatic artery should be performed with gentle, sharp dissection, especially in patients who have received prior chemotherapy or chemoradiation and in those with extensive peritumoral inflammation from a previous laparotomy or stent-related pancreatitis. Blunt dissection at the GDA origin can result in intimal dissection of the hepatic artery. Division of the GDA allows mobilization of the hepatic artery and exposure of the anterior surface of the PV directly posterior to the inferior border of the CHA. The PV should always be exposed in this way before dividing the common hepatic duct. Care during this critical step in the performance of PD can minimize trauma to the hepatic artery and allow for a secure closure of the GDA stump [22].

GDA Ligation

Occasionally, ligation of the GDA is complicated by close proximity of the pancreatic tumor. If the tumor extends to within a few millimeters of the GDA, our technique is to obtain proximal and distal control of the hepatic artery and then divide the GDA flush at its origin. The resulting arteriotomy can be closed primarily with interrupted 6-0 prolene sutures. If 2 mms of GDA origin is available, we often use a small vascular pledget, as the hepatic artery can be quite fragile in this location; if the arteriotomy is flush with the CHA, a pledget cannot be used. When the tumor extends to the GDA origin, we divide the GDA prior to any form of ligation of the distal GDA on the specimen side. The GDA on the specimen side is suture ligated with 4-0 Prolene after it is divided; control of back-bleeding from this vessel is easily accomplished with simple hand pressure if a complete Kocher maneuver was performed earlier in the operation. This maneuver decreases trauma and handling of the GDA and decreases chances of intimal dissection of the hepatic artery [22]. When adequate length of GDA allows for a simple ligation, we usually use a 0-silk tie on the hepatic artery side with a 4-0 Prolene suture on the specimen side (so as to avoid unnecessary mobilization which is often needed to place a tie distally on the specimen side).

Reinforcing the Pancreatic Transection Site (Distal Pancreatectomy)

When performing a distal or subtotal pancreatectomy, the remnant pancreas can lead to a potential pancreatic fistula and subsequent PPH from a splenic artery pseudoaneurysm. We routinely divide the pancreas and perform the pancreatic closure either with Gore-Tex reinforced staples or with pledgeted sutures. The limitation to using the stapler is in proximal neck/body tumors where there is limited room (due to the proximity of the intrapancreatic bile duct) for achieving an adequate margin. In addition, as one moves to the patient’s right of the pancreatic neck (and enters the region of the pancreatic head), the pancreas becomes too thick for a staple line. In this scenario, after confirming a negative margin, we identify the pancreatic duct and close it directly with a horizontal mattress suture. We then close the remaining pancreas with additional horizontal mattress sutures with a pledget on both the posterior and anterior surfaces (Fig. 26.3). The first such pledgeted suture is placed at the site of the pancreatic duct so that the duct closure is covered by the location of the pledget. Both a stapled closure and a suture closure with pledgets are done to minimize the risk of pancreatic fistula, which can increase the risk of PPH.

Fig. 26.3
figure 3

Intraoperative photograph of a completed distal pancreatectomy. Arrowheads point to the cut margin of the pancreas closed with pledgeted sutures. CHA common hepatic artery, SMA superior mesenteric artery, SMV superior mesenteric vein

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Diagnosis of Late PPH

Symptoms/Signs

The occurrence of a sentinel bleed is a key sign and symptom of late PPH [8, 16]. Sentinel bleeding refers to isolated bleeding, usually from the gastrointestinal tract or an abdominal drain/drain site. It implies the presence of a structural vascular defect and requires immediate evaluation [23]. Sentinel hemorrhage, as mentioned previously, is often associated with local sepsis and an anastomotic leak; it is uncommon to see late PPH in a patient who has had a completely uneventful postoperative course [24]. Patients who develop a sentinel bleed, as defined as a low volume of hemorrhage in a patient who is hemodynamically stable at the time of the event, are at high risk of developing massive hemorrhage and should undergo diagnostic and therapeutic intervention as soon as possible [7, 8, 16]. The second episode of bleeding may follow in minutes or hours and is often severe, being accompanied by hemodynamic instability and a high risk of mortality. Vigilance is critically important, as up to 90 % of patients who experience PPH have been through a turbulent postoperative period characterized by some form of intra-abdominal infection. Those patients who have had conservative management or radiological interventions for intra-abdominal fluid collections are at particularly high risk, and therefore, a sentinel hemorrhage in this setting warrants immediate attention [7, 16].

Imaging for Late PPH

Management of the exsanguinating patient with late PPH is unlikely to be successful and therein lies the rationale for immediate action in the setting of a sentinel bleed. A patient presenting with a sentinel bleed should undergo immediate angiography. If the diagnosis of a sentinel bleed is less clear, for example, the blood in the drain may have been associated with accidental traction on the drain, or the issue of a possible melanotic stool is in question, then CT imaging prior to angiography is quite reasonable. Ultrasound imaging may depict a false aneurysm but has no role in the investigation of acute bleeding. CT angiography may reveal the cause, site, and nature of bleeding if contrast extravasation is seen or a pseudo-aneurysm is visualized. A triple-phase examination (unenhanced, arterial, and venous phases) is performed with iodinated contrast material. Images are reviewed with multiplanar reformatting, which contributes to the diagnosis and aids in the planning of endovascular or surgical intervention. Unenhanced scans depict collections and high attenuation from beam-hardening and streak artifacts that can mimic bleeding. The arterial phase may reveal active contrast extravasation from the arterial anatomy. The venous phase may show contrast pooling and other complications that can follow a Whipple procedure [25, 26].

If CT imaging does not yield a focus for the bleeding and the patient becomes unstable or an unequivocal sentinel bleed were to occur, the patient should move directly to selective angiography without delay. Caution should be taken in interpreting the results of angiography if a bleeding site is not seen, as a negative examination does not rule out a late PPH. The intermittent nature of the bleeding can hamper detection by angiography even in patients with severe stigmata of bleeding. The importance of angiography cannot be overstated: first, embolization can be performed if the bleeding site is located and second, the alternative treatment to consist of reoperation is unlikely to be successful [27]. Emergent reoperative laparotomy in an effort to expose the GDA stump in an unstable patient stands a very low likelihood of being successful even if performed by a very experienced surgeon. The main (and perhaps only) hope for a good patient outcome rests in the interventional radiology suite, not the operating room. If the site of bleeding is uncertain, angiography of the celiac axis and SMA should be performed. Active contrast extravasation and pseudoaneurysms can be managed therapeutically when the diagnosis is made. Spasm and irregularity of a vessel are indirect signs of a source of bleeding. If extravasation from the expected sites is not seen, selective/superselective angiography can be performed [27].

Management of PPH

Early PPH

Management of early PPH should consist of resuscitation and in general, emergent return to the operating room for laparotomy. Very rarely, gastrointestinal hemorrhage early in the postoperative period can be managed endoscopically. Therapeutic endoscopy may permit the successful management of a bleeding point in the gastrojejunostomy, which would be the only indication for endoscopy early in the postoperative setting. However, the pancreaticojejunostomy would be more likely to be the source of hemorrhage rather than the gastrojejunostomy. Patients with intra-abdominal bleeding, whether evident from a surgically placed drain or due to progressive expansion of the abdomen on examination, require reoperation, and a delay should not occur [12–14].

Late PPH

Patients with late PPH should undergo emergent selective angiography and if the source is found, embolization of the bleeding vessel should be performed. Embolization is successful in up to 80 % of patients although this complication is uncommon and reports are largely anecdotal or consist of small series from large referral institutions. As noted previously, the key to preventing mortality is rapid recognition and prompt management. Postoperative gastrointestinal or drain tract bleeding should prompt immediate evaluation with arteriography. Gastrointestinal or drain tract bleeding represents a true medical emergency as the only patients likely to survive are those in whom the diagnosis is made immediately. Although individual surgeon experience with this complication is largely anecdotal, stenting of the hepatic artery or the more conventional embolization of the hepatic artery may both be successful. In the setting of a normal bilirubin, the liver will usually tolerate hepatic artery embolization when it is performed a few weeks after the hepaticojejunostomy. Multisystem organ failure and death usually result from the infectious complications and the excessive blood loss which may accompany/often accompanies this complication [22].

Embolization sacrifices distal blood flow but is the only alternative for areas where anatomy is complex and vessels are small [27]. The embolic materials used are coils, glue, thrombin, and absorbable gelatin sponge. Coils are commonly used and suitable when there is a single feeding vessel which can be sacrificed. It is essential to embolize both the inflow and outflow vessels or bleeding may recur. Balloon occlusion can be used for protection of distal circulation but tissue infarction is more likely than with coils. Stent grafting preserves distal perfusion, such as that to the liver and spleen, but can be impossible in tortuous and small vessels. Intentional dissection is an option if the bleeding site cannot be reached selectively for embolization [28, 29].

Pseudoaneurysms that persist after embolization can be managed with percutaneous injection of thrombin under ultrasound or CT guidance [16, 29]. The GDA stump is the most common cause of active extravasation or pseudoaneurysm formation. A bleeding source in the common or proper hepatic arteries can also occur as the result of a pancreatic leak. Covered stents are useful and have the added benefit of preserving distal perfusion. Celiac axis erosion is uncommon, and endovascular stent grafting is an option for management although this procedure may involve sacrificing either the hepatic or the splenic artery. An alternative is to embolize the whole vessel to ensure that there is no back filling from the celiac axis branches [30].

Splenic artery pseudoaneurysm is uncommon and when it occurs, is once again usually secondary to a pancreatic leak or intraoperative infection. Management depends on the site of extravasation and the tortuosity of the splenic artery. A covered stent can be used in straight arteries; in tortuous vessels, embolization is required. Proximal lesions can be embolized with preservation of splenic perfusion via the short gastric arteries as the left gastric artery is preserved and remains the main source of gastric perfusion. Embolization of distal lesions increases the risk of splenic infarction.

IPDA pseudoaneurysms are rarely seen after the Whipple procedure but when they occur, they are the result of a local infection (pancreatic leak) or abscess formation adjacent to the SMA. If bleeding is present, the problem can be managed with embolization or stenting.

Hemobilia due to a hepatic artery pseudoaneurysm with involvement of the residual common bile/hepatic duct in the inflammatory process can manifest itself as false extraluminal bleeding. The hepatic artery can be managed with embolization [29–31].

Conclusion

Complication rates for pancreatectomy still persist due to the large magnitude of the operation which is usually performed in patients of advanced age with associated comorbidities. PPH is one of the major causes of morbidity and mortality after PD. PPH can be divided into early and late postoperative bleeding. Early PPH is that which occurs within 24 h of surgery. It often is caused by technical failure of appropriate hemostasis during the index operation (failure to perform the SMA dissection correctly and to identify and ligate the IPDAs) or by an underlying perioperative coagulopathy. Late PPH occurs more than 24 h after the operation and typically one or more weeks from the date of surgery. Late PPH is associated with more common complications of the operation, most notably a leak from the pancreaticojejunostomy. Local sepsis from a pancreatic fluid collection or intra-abdominal abscess may erode the vascular wall adjacent to a loop of bowel leading to PPH. Prevention of PPH depends both on careful dissection of the portahepatis and the hepatic artery/GDA and on creation of a pedicled falciform ligament flap to protect the vessels from possible pancreatic fistula and fluid collections. For patients who receive a distal pancreatectomy, reinforcement of the pancreas transection site with Gore-Tex or pledgeted sutures can also be followed with falciform ligament flap coverage. The occurrence of a sentinel bleed is a key sign which often occurs before the onset of late PPH. Patients who develop a sentinel bleed, especially those who have had a complicated/septic postoperative period have a high risk of developing imminent massive hemorrhage and should undergo immediate diagnostic and therapeutic angiography.

Management of early PPH depends on whether the bleeding is located intraluminally or extraluminally. Interventional endoscopy is occasionally indicated when intraluminal PPH is suspected to originate from the gastrojejunostomy; reoperation is usually the treatment of choice for early PPH and in all cases where the blood is intra-abdominal (extraluminal). In the case of a late PPH usually associated with pancreatic fistula formation, angiography is the intervention of choice and should be performed without delay. If the source cannot be found at the first attempt at angiography, re-angiography may be performed within 6–24 h. The best solution to the problem of late PPH is prevention—a carefully performed operation and use of vascularized tissue to separate the hepatic artery from the afferent jejunal limb to include careful coverage of the GDA stump.

Key Points to Avoid Complications

  1. 1.

    Preserve the falciform ligament (obliterated umbilical vein) for use as coverage of the GDA stump, vascular anastomoses, or the splenic artery stump (in the case of a distal pancreatectomy).

  2. 2.

    When a distal pancreatectomy is performed, the falciform ligament can be sutured to the remnant pancreas allowing for complete separation of the adjacent vessels from the pancreas in the event of a pancreatic fistula.

  3. 3.

    Dissection of the hepatic artery should be performed with gentle, sharp dissection. Blunt dissection, especially at the GDA origin, can result in intimal dissection of the hepatic artery.

  4. 4.

    If the tumor extends to within a few millimeters of the GDA origin, our technique is to obtain proximal and distal control of the hepatic artery and then divide the GDA flush at its origin.

  5. 5.

    We routinely reinforce our remnant pancreatic transection with stapled Seamguard (Gore, Newark, DE) or pledgeted sutures.

Key Points to Diagnose/Manage

  1. 1.

    The occurrence of a sentinel bleed is a key sign, which often signals the onset of a significant PPH.

  2. 2.

    A patient presenting with an obvious sentinel bleed (acute blood loss of gastrointestinal (hematemesis or melena) or drain-site origin) should undergo immediate angiography in search of a pseudoaneurysm.

  3. 3.

    If the presence or absence of a sentinel bleed is not obvious (trace amount of blood at a drain site or a drop in hemoglobin in the absence of hematemesis or melena), a contrast-enhanced CT scan is indicated.

  4. 4.

    Patients who are found to have extraluminal PPH (most commonly the GDA stump) should undergo embolization or stent placement.

  5. 5.

    Splenic artery pseudoaneurysms are uncommon and most often secondary to a pancreatic leak or intraoperative trauma.

Disclosures

No funding sources or conflicts of interests.