|Year : 2020 | Volume
| Issue : 7 | Page : 1672-1677
Portal hypertension caused by pancreatic cancer: Multidetector computed tomography diagnosis and multivariate analysis of variceal hemorrhage
Guo-Ping Liu1, Xiao-Kun Hu2, Zhao-Long Zhang2, Rui Xu2, Cheng-Jian Sun2, Yong-Ning Xin3, Shi-Ying Xuan3
1 Department of Clinical Medicine, Medical College of Qingdao University; Department of Interventional Medical Center, The Affiliated Hospital of Qingdao University, Qingdao, China
2 Department of Interventional Medical Center, The Affiliated Hospital of Qingdao University, Qingdao, China
3 Department of Clinical Medicine, Medical College of Qingdao University; Department of Gastroenterology, Qingdao Municipal Hospital, Qingdao, China
|Date of Submission||21-Apr-2020|
|Date of Decision||13-Oct-2020|
|Date of Acceptance||01-Dec-2020|
|Date of Web Publication||9-Feb-2021|
1 Jiaozhou Road, Qingdao, Shandong Province
Source of Support: None, Conflict of Interest: None
Context: Pancreatic cancer portal hypertension (PCPH) is a rare cause of gastrointestinal bleeding. This study retrospectively assessed gastrointestinal bleeding risk factors in 57 PCPH patients diagnosed via multidetector computed tomography (MDCT).
Materials and Methods: The data of patients with pancreatic cancer from January 2008 to January 2018 at Qingdao Municipal Hospital were reviewed. PCPH patients were screened with MDCT and followed up. MDCT findings (e.g., the location of the venous obstruction, type of variceal veins pathway, and splenomegaly) were recorded. Variceal hemorrhage was recorded. The MDCT findings and clinical data of the PCPH patients were used in this analysis to explore the risk factors of variceal hemorrhage using binary logistic regression and multivariate logistic regression model.
Results: Fifty-seven of the 182 patients were diagnosed with PCPH. A total of 7 draining routes and 11 types of varices were found. Of these patients, eight experienced variceal hemorrhage. Univariate analysis showed that splenomegaly (odds ratio [OR] = 10.364, P = 0.003) was significantly associated with an increased risk of variceal hemorrhage. Multivariate analysis showed that splenomegaly (OR = 66.491, 95% confidence interval: 2.790–1584.643, P = 0.009) was an independent influencing factor for variceal hemorrhage in PCPH patients.
Conclusions: Patients with pancreatic cancer have high morbidity of PCPH. The splenomegaly is more prone to hemorrhage. Splenomegaly was an independent risk factor of variceal hemorrhage. MDCT can provide insight into the stenosis and occlusion of the portal vein system and the drainage routes of variceal veins and is one of the best ways to diagnose PCPH.
Keywords: Gastroesophageal varices, gastrointestinal hemorrhage, multidetector computed tomography, pancreatic cancer, portal vein occlusion, splenic vein occlusion, splenomegaly
|How to cite this article:|
Liu GP, Hu XK, Zhang ZL, Xu R, Sun CJ, Xin YN, Xuan SY. Portal hypertension caused by pancreatic cancer: Multidetector computed tomography diagnosis and multivariate analysis of variceal hemorrhage. J Can Res Ther 2020;16:1672-7
|How to cite this URL:|
Liu GP, Hu XK, Zhang ZL, Xu R, Sun CJ, Xin YN, Xuan SY. Portal hypertension caused by pancreatic cancer: Multidetector computed tomography diagnosis and multivariate analysis of variceal hemorrhage. J Can Res Ther [serial online] 2020 [cited 2021 Feb 28];16:1672-7. Available from: https://www.cancerjournal.net/text.asp?2020/16/7/1672/308767
| > Introduction|| |
Pancreatic cancer portal hypertension (PCPH), part of the pancreatogenic portal hypertension (PPH), commonly occurs in patients with pancreatic cancer, secondary to tumor invasion or compression to the portal system (portal vein [PV], superior mesenteric vein [SMV], splenic vein [SPV], SMV-PV confluence).,,
In addition to the clinical manifestations of pancreatic cancer (e.g., abdominal pain, alexithymia, weight loss), the clinical manifestation of PCPH also includes refractory diarrhea, ascites, and esophagogastric varices. Variceal hemorrhage is one of the most severe complications of PCPH. Splenectomy, endoscopic injection sclerotherapy (EIS), endoscopic variceal band ligation (EVL), partial splenic embolization (PSE), and percutaneous transsplenic varices embolization (PTVE) are standard treatments for PCPH with variceal hemorrhage in most cases; yet the treatment of PPH patients without variceal hemorrhage remains controversial.
PCPH diagnosis is primarily based on radiological evaluations, endoscopy, and operative findings. Radiology is widely used to detect pancreatic and adjacent vessel lesions in a noninvasive and repeatable manner. Multidetector computed tomography (MDCT) can accurately describe the location, type of varices, and hemodynamic change.
Identifying patients at high risk for variceal hemorrhage complications may help improve patient outcomes in future. Here, we aimed to explore the relevant risk factors for variceal hemorrhage and provide a basis for clinical treatment. The clinical data and imaging findings of PCPH patients were retrospectively analyzed to determine potential variceal hemorrhage risk factors.
| > Materials and Methods|| |
The Ethics Committee of Qingdao Municipal Hospital approved this retrospective study, and informed consent was waived. The medical records were screened for all patients between January 2008 and January 2018 at Qingdao Municipal Hospital with pancreatic cancer. Patients diagnosed with cirrhotic portal hypertension, PV thrombosis, cavernous transformation of the PV, and PCPH patients that underwent curative resection, splenectomy, or regional portal hypertension caused by nonpancreatic cancer were excluded from this study.
Computed tomography imaging and diagnostic criteria
All patients underwent three-phase enhanced multi-slice computed tomography (CT) abdominal imaging, which included a thin-layer scan. The diagnostic criteria of PCPH were (1) pancreatic cancer confirmed by the pathology of the pancreatic lesion or liver metastasis tumor using endoscopic ultrasonography-guided fine-needle aspiration, needle biopsy, or operation; (2) a portal phase thin-layer scan showing significant stenosis or occlusion of the splenic, SMV, or lower PV; (3) increased and expanded vein collateral vessels and ectopic varices at the splenic hilus, peri-gastric, peri-pancreatic head. Patients with nonvariceal gastrointestinal bleeding, such as peptic ulcers, gastrointestinal tumors, hemorrhagic gastroenteritis, or hemorrhages of the diverticulum, were excluded from this study.
Patient records and follow-up
Patients diagnosed with PCPH were assessed to determine whether variceal gastrointestinal bleeding occurred during the course of the disease and in cases of death, whether the death was attributed to variceal gastrointestinal bleeding. Patient data were collected through direct correspondence, official medical records, or an outpatient appointment. The primary end-point of this study was death. Outcome measures included sex, age, location of the venous obstruction, type of variceal veins pathway, and splenomegaly. Observational indicators included sex, age, the venous obstruction sites, varices types, and splenomegaly.
Statistical analysis was performed using SPSS 19.0 software from IBM (Chicago, IL, USA). The relationship between variceal hemorrhage and clinicopathological features was analyzed using binary logistic regression. The multivariate logistic regression model was used for multivariate analysis. P < 0.05 were considered statistically significant.
| > Results|| |
Multidetector computed tomography findings
Of the 182 patients, 57 patients were diagnosed with PCPH. There were seven variceal drainage routes (denoted as 1–7): (1) splenic vein-PV pathway, including splenic vein-short gastric vein-gastric wall-gastric coronal vein-PV, splenic vein-short gastric vein-gastric wall-coronary vein of the stomach-unoccluded segment of the splenic vein-PV; (2) splenic vein-SMV, including the splenic vein-left gastroepiploic vein-right gastroepiploic vein-SMV, splenic vein-left colonic vein-SMV; (3) SMV-peri-pancreatic head vein-PV; (4) splenic vein-stomach vein-esophagus vein-azygos vein-superior vena cava; (5) renal vein shunt, including spleno-gastro-renal shunt-inferior vena cava, splenorenal shunt-inferior vena cava; (6) splenic vein-short gastric vein-coronary vein-pericardiacophrenic veins-brachiocephalic vein; and the (7) splenic vein-short gastric vein-coronary vein-liver.
There were 11 types of varices found in this study. The types of draining routes are described in [Table 1]. The most common type is 1+2, accounting for 33 cases, followed by 1,1+2+3, 1+4. As expected, the vascular occlusions at different anatomical locations led to different variceal pathways. [Figure 1] describes the common variceal draining routes for occlusions of different locations. Eventually, the splenic vein and mesenteric vein blood flowing through the varices terminate into the PV, liver, superior vena cava, and inferior vena cava.
|Figure 1: The common variceal draining routes for occlusions of different location. SV = Splenic vein, SVO = Splenic vein occlusion, SVC = Superior vena cava, SMV = Superior mesenteric vein, SHV = Splenic hilus vein, SGV = Short gastric vein, SPJO = Splenoportal junction occlusion, NSVO = Nonsplenic vein occlusion, PV = Portal vein, PSVO = Pure splenic vein occlusion, PCPV = Pericardiacophrenic vein, PPHV = Peri-pancreatic head vein, GCT = Gastrocolic trunk, GW = Gastric wall, LGEV = Left gastroepiploic vein, LCV = Left colic vein, LRV = Left renal vein, RGEV = Right gastroepiploic vein, IMV = Inferior mesenteric vein, IVC = Inferior vena cava, EV = Esophagus vein, GCV = Gastric coronary vein, GRS = Gastrorenal shunt, AV = Azygos vein|
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|Table 1: Types of draining routes in the 57 patients with pancreatic cancer portal hypertension|
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MDCT found enlarged veins, including short gastric varices [Figure 2], gastroepiploic varices [Figure 3], gastric coronary varices [[Figure 4] and [Figure 5], and esophageal varices [Figure 6].
|Figure 2: A 63-year-old woman with pancreatic cancer portal hypertension. Computed tomography scan shows short gastric varices (black arrow)|
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|Figure 3: A 59-year-old man with pancreatic cancer portal hypertension. Computed tomography scan shows left gastroepiploic vein (white arrow) and pancreatic lesion (black arrow)|
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|Figure 4: A 71-year-old man with pancreatic cancer portal hypertension. Computed tomography scan shows (a) portal vein (white arrow), gastric coronary vein collateral vessel (black arrow). (b) Portal vein (thick white arrow), collateral vein (white arrow), and superior mesenteric vein (thick black arrow). There was severe stenosis at the junction of mesenteric vein and portal vein. Gastric coronary vein collateral vessel blood flow directly into the liver|
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|Figure 5: A 63-year-old man with pancreatic cancer portal hypertension. Computed tomography scan shows (a) pancreatic lesion (white arrow), liver metastasis (black arrow), gastric coronary vein (thick white arrow) and gastroepiploic vein (thick black arrow). (b) Two months later, the patient developed melena. The digital subtraction angiography before partial splenic embolization shows enlarged liver metastasis (black arrow), gastric coronary vein (thick white arrow), and gastroepiploic vein (thick black arrow)|
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|Figure 6: A 53-year-old man with pancreatic cancer portal hypertension. Computed tomography scan shows around the esophageal varices (white arrow)|
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Clinical characteristics of variceal hemorrhage patients
In total, there were eight cases of PCPH with variceal hemorrhage. Endoscopy was performed in all eight patients; In which six patients had isolated gastric varices 1 (IGV1), and two patients had gastric esophageal varices 2 (GOV2). One patient initially presented with gastrointestinal tract hemorrhage, which was later confirmed as the result of PCPH. Based on the patients' condition and the treatment intentions, hemostatic drugs, splenectomy, EIS and EVL, PSE, or PTVE were performed. Rescue splenectomy combined with distal pancreatectomy effectively treated one patient who still experienced bloody stool after EIS treatment. The clinical characteristics of these eight cases are shown in [Table 2].
|Table 2: Clinical characteristics of pancreatogenic portal hypertension patients with complicated hemorrhage|
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Univariate analysis of pancreatogenic portal hypertension with variceal hemorrhage
Univariate analysis showed that splenomegaly (odds ratio [OR] = 10.364, P = 0.003) was significantly associated with variceal hemorrhage. The age, gender, PV occlusions, and short gastric vein varices were not associated with variceal bleeding (P > 0.05), as shown in [Table 3].
|Table 3: Univariate analysis of variceal hemorrhage in patients with PCPH|
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Multivariate analysis of pancreatogenic portal hypertension with variceal hemorrhage
Multivariate analysis of significant independent variables in the logistic regression model's univariate analysis showed that splenomegaly (OR = 66.491, 95% confidence interval [CI]: 2.790–1584.643, P = 0.009) is an independent risk factor for variceal bleeding in patients with PCPH, as shown in [Table 4].
|Table 4: Multivariate logistic regression analysis of variceal hemorrhage in pancreatogenic portal hypertension|
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| > Discussion|| |
The most common etiology of PPH is pancreatitis,, but pancreatic cancer may also cause the disorder. In this study, 57 of 182 patients (57/182; 31.32%) with pancreatic cancer were diagnosed with PCPH.
Enhanced MDCT thin-layer imaging revealed the primary disease of the pancreas, the site of stenosis or occlusion, and the drainage routes of variceal veins in patients with PCPH.,,, MDCT has been used to evaluate the PV and its tributaries in previous articles.,,, Previously, Perri et al. advocated that MDCT can be used to detect esophageal or gastric varices, especially the peri-esophageal and extra-luminal varices, that may be missed with traditional endoscopy. In agreement, Tseng et al. demonstrated that CT detection of gastroesophageal varices could be used in place of esophagogastroduodenoscopy as a primary screening tool for diagnosing GOV and that MDCT has better sensitivity for detecting submucosal lesions compared with conventional esophagogastroduodenoscopy. It is also possible to evaluate the normal left gastric vein using MDCT. In this study, MDCT was used to clearly visualize varices of different anatomical locations, including short gastric varices, gastroepiploic varices, enlarged gastric coronary veins, esophageal varices.
In addition to gastric varices, MDCT can also visualize the draining routes of gastric varices.,, In this study, 7 different varices and 11 types of draining routes were observed through MDCT [Table 1]. The different draining routes of varices were found by tracing the continuous thin-layer scans of the MDCT.
Bleeding occurs in varices located under the mucosa of the gastrointestinal tract. In patients with PCPH, there is retrograde blood flow through the short gastric and gastroepiploic veins, leading to the formation of the IGV1, IGV2, and GOV. The varices surrounding the pancreatic head arise from the SMV to the PV, forming the ectopic varices. The gastroepiploic vein is often located outside the digestive tract wall and occasionally forms the IGV2 or ectopic varices. The short gastric vein varices form most IGV1s and GOVs and are the most common varices under the gastrointestinal tract mucosa in PCPH. The direction of blood flow after forming short gastric vein varices was that through gastric left vein to PV, through gastric vein to esophageal vein, and through the gastro-renal shunt to the left renal vein.
Patients with pancreatic cancer may initially present with bleeding gastric varices. In this study, one patient with gastrointestinal tract hemorrhage was found to have gastric varices, pancreatic lesions, and PV occlusion by endoscopy and MDCT. Smith and Brand reported two similar cases.
In this study, the bleeding rate of variceal ruptures in 57 PCPH patients was 14.04% (8/57). The PV occlusions and the short gastric vein varices had no significant correlation with variceal hemorrhage (P > 0.05). However, the ratio of bleeding patients in patients with PV occlusion (4/16) was significantly higher than patients without PV occlusion (4/41). All eight bleeding patients were cases with short gastric vein varices (8/48). Short gastric varices have always been considered contributing factors of bleeding in PCPH because they indicate that the splenic portal blood flows through the stomach to the PV due to an obstruction of the splenic vein. The coronary vein drains to different parts of the portal system, including the splenic vein, junction part, and PV. PV occlusions destroy the gastric coronary vein's outflow tract, which increases venous pressure in the spleen and stomach region and promotes the formation of esophageal varices. All of these factors increase the risk of varices bleeding. Nagai et al. revealed that PV occlusion, no PV – splenic vein patency, and splenic vein ligation were found to be significant risk factors for late-onset gastrointestinal hemorrhage. This study revealed that splenomegaly was significantly correlated with variceal hemorrhage (OR = 10.364, P = 0.003). PCPH patients with splenomegaly are more likely to develop variceal bleeding. Multivariate logistic regression analysis indicated that splenomegaly was an independent risk factor for variceal hemorrhage (OR = 66.491, 95% CI: 2.790–1584.643, P = 0.009). There were 6 variceal bleeding patients in 17 patients with splenomegaly and 2 variceal bleeding patients in 40 patients without splenomegaly (35.29% vs. 5.00%). A splenomegaly could increase the blood flow in variceal veins, as it is associated with increased splenic blood flow and significantly associated with variceal bleeding. On the other hand, occlusion of the PV and splenic vein could increase the pressure of the splenic outflow tract and enlarge the spleen. In addition, splenorenal or spleno-gastro-renal shunts can reduce the pressure of the spleen and stomach region veins. There were two cases of shunts in this study, which is similar in terms of incidence reported in previous studies.
Splenectomy is commonly used to treat PCPH patients with variceal bleeding due to its effectiveness., However, many complications are associated with splenectomies, including postsurgical infections, PV thrombosis, and carcinomas.,, Pancreatic cancer has often been diagnosed too late for surgery. Currently, interventional radiology treatments, such as PSE, PTVE plus PSE, and percutaneous splenic vein recanalization, have been successfully applied to the treatment of PPH variceal bleeding., Liu et al. found similar success rates between PSE and surgical procedures and advocated that PSE should be selected as the first-line treatment for PPH patients with bleeding. In agreement, Wang et al. described PSEs feasibility and effectiveness in treating 14 PPH patients with gastric varices or gastric variceal bleeding. Among the eight patients, one died of massive gastrointestinal bleeding after EIS treatment. One underwent splenectomy and distal pancreatectomy after the recurrence of bloody stool post-EIS treatment; the patient had no further bleeding. Three cases underwent PSE, of which two cases had succedent intermittent fecal occult blood test positive. No further gastrointestinal bleeding arose in the two cases who underwent splenectomy and EIS + PSE treatment, respectively. One case was intermittent fecal occult blood test-positive after drug hemostasis. The latter seven patients died of nongastrointestinal bleeding.
This study was limited to the single-center experience and a relatively small sample population. In future, multi-center trials with larger sample populations should be used to verify these findings.
| > Conclusion|| |
Patients with pancreatic cancer have high morbidity of PCPH. The splenomegaly is more prone to hemorrhage. Splenomegaly was an independent risk factor of variceal hemorrhage. MDCT can provide insight into the stenosis and occlusion of the portal vein system and the drainage routes of variceal veins and is one of the best ways to diagnose PCPH.
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Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6]
[Table 1], [Table 2], [Table 3], [Table 4]