Pancreatic cancer initially presenting with acute renal infarction: A case report

Abstract

BACKGROUND

Pancreatic carcinoma is recognized as one of the most prothrombotic malignancies, carrying a high risk of thrombotic events, which may even precede the diagnosis of the underlying occult tumor. Acute renal infarction (ARI) as the initial presenting feature in patients with pancreatic cancer is a rare occurrence, and misdiagnosis is common during early evaluation.

CASE SUMMARY

We report a patient who presented with ARI as the initial manifestation prior to the diagnosis of pancreatic cancer. The 50-year-old male was admitted to our emergency department with sharp, left-sided abdominal pain and was subsequently transferred to our department following the detection of a pancreatic space-occupying lesion on computed tomography (CT). CT angiography promptly identified the cause of his pain, confirming right renal infarction. Urgent interventional treatment was initiated to alleviate symptoms and restore renal perfusion. Despite aggressive thrombolytic and anticoagulant therapy, the thrombotic event rapidly worsened, leading to multiple cerebral infarctions. The patient’s condition ultimately deteriorated under palliative care.

CONCLUSION

This case illustrates that arterial thromboembolism, when diagnosed at an advanced stage of pancreatic cancer, appears to be a terminal event that portends a poor prognosis. Establishing an arterial thrombosis prediction model will potentially identify the profile of high-risk patients with thrombotic consequences for primary prevention.

Key Words: Acute renal infarction; Pancreatic cancer; Trousseau syndrome; Anticoagulation; Case report

Core Tip: We describe a 50-year-old male patient who presented with acute renal infarction as the initial manifestation prior to the diagnosis of pancreatic cancer. Given its low incidence and nonspecific clinical symptoms, diagnostic suspicion and prompt initial intervention are crucial for achieving a favorable clinical prognosis.

INTRODUCTION

It has been established that pancreatic carcinoma is characterized by a systemic cancer-induced hypercoagulable state, which poses a high risk of developing thromboembolic complications[1,2]. The prothrombotic malignancy enables to express tissue factor, to release neutrophil extracellular traps, and to disseminate tumor-derived micro-vesicles. These procoagulant factors and other potential mechanisms collectively contribute to coagulation, platelet aggregation and endothelial function impairment, resulting in thrombotic events[3,4].

Traditionally, the main consideration of thrombotic events has been given to venous thromboembolism (VTE) in patients with pancreatic cancer, which commonly encompasses deep venous thrombosis and pulmonary embolism. However, arterial thromboembolic (ATE) events are yet a neglected field[3]. ATEs are relatively uncommon in patients with pancreatic cancer, with an estimated incidence of 2%-6%[5,6]. A retrospective matched-cohort analysis published in 2017 identified 12279 patients with pancreatic adenocarcinoma between 2002 and 2011[7]. The cumulative risk of ATE at 6 months was 5.9% (95%CI: 5.5-6.4) compared to 2.4% (95%CI: 2.1-2.7) in the control cohort (P < 0.001), which indicates that patients newly diagnosed with pancreatic cancer faced a considerably increased short-term incidence of developing ATE. Embolism has been commonly recognized as a life-threatening complication of cancer, with poor prognosis. The events predominantly manifest as myocardial infarction and cerebrovascular, diseases that are hardly incidental due to their grave clinical consequences. ATEs involving other sites, including mesenteric and iliofemoral artery thrombosis, have also been sporadically reported[8].

Nevertheless, pancreatic cancer presenting with acute renal infarction (ARI) as the first manifestation is rarely seen but occurs occasionally, and its early diagnosis remains a challenge. Herein, we present a Chinese patient presenting with acute abdomen, subsequently diagnosed with ARI, which served as the initial clinical manifestation of pancreatic cancer.

CASE PRESENTATION

Chief complaints

A previously healthy 50-year-old male presented to the emergency department with sudden severe left-sided abdominal pain.

History of present illness

Left-sided abdominal pain manifested upon awakening and progressively intensified, persisting for approximately 12 hours. The pain was aggravated when the patient was in the supine position but could be relieved when the patient maintained the anterior tilt position. There was no tenderness or rebound pain in the abdomen during physical examination. Upon admission to the hospital, serum and urinary amylase were negative. Abdominal computed tomography (CT) was performed to rule out acute pancreatitis. However, the CT scan revealed a space-occupying lesions in the pancreatic tail and multiple masses in the liver. Understandably, at that time, the pain was preliminarily considered to be caused by tumor infiltration and compression of the abdominal nerve plexus. The patient was subsequently hospitalized for further treatment and initiated on opioid therapy; however, no significant pain relief was achieved. He denied diarrhea, fever or hematuria, and there was no history of gastrointestinal disease or heart disease.

History of past illness

The patient was previously in good health. No significant past medical history.

Personal and family history

The patient had a significant history of long-term tobacco use (approximately one pack per day for more than 30 years, with a smoking index of 600). He had no family history of malignancies, psychological or genetic disorders.

Physical examination

His vital signs remained within normal limits. No icteric discoloration was observed on the skin or sclera. Further physical examination revealed tenderness upon percussion in the right renal area. McBurney’s point tenderness and Murphy’s sign were both negative.

Laboratory examinations

Blood tests revealed D-dimer levels of 18.14 mg/L (reference range: 0-0.5 mg/L) and fibrinogen degradation products at 65.8 μg/mL (reference range: 0-5 μg/mL). Serum tumor marker analysis showed CA199 at 36418 U/mL (reference range: < 30 U/mL), CA125 at 3058 U/mL (reference range: 0-24 U/mL), and CEA at 75.77 ng/mL (reference range: 0-5 ng/mL). Blood biochemistry results indicated a urea level of 7.8 mmol/L (reference range: 3.1-8 mmol/L) and creatinine level of 102 μmol/L (reference range: 57-97 μmol/L). Bilirubin, alanine aminotransferase, and aspartate aminotransferase levels were within the normal reference ranges.

Imaging examinations

Combined with the discrepancy between the self-symptom and objective signs, we speculated on the possibility of thrombotic diseases and performed total abdominal CT angiography (CTA) and enhanced CT. The mesenteric artery CTA scan showed no significant abnormalities. However, a filling defect was visible in the anterior branch of the right renal artery, suggesting embolus formation, and the right kidney was abnormally enhanced (Figures 1A and 2A-D). Therefore, right renal infarction was diagnosed. Meanwhile, the abdominal CT suggested a soft tissue mass, approximately 4.0 cm × 2.6 cm in size, at the pancreatic tail with a poorly defined boundary, uneven internal density and liquefaction necrosis. On the enhanced scan, the lesion showed mild uneven enhancement, with a slightly high-density shadow in the surrounding adipose space. In addition, multiple round, variably sized and low-density shadows were scattered within the liver. Uneven inner density, circular enhancement, and unclear boundaries were observed on the enhanced scan (Figures 1B, 2A and 2B).

Figure 1 Abdominal contrast-enhanced computed tomography images were obtained during the arterial phase, portal phase, and equilibrium phase. A: Right renal infarction (orange arrow); B: Pancreatic cancer (yellow arrow) with hepatic metastasis. M: Metastasis.

Figure 2 Abdominal computed tomography three-dimensional reconstruction images, angiogram-three-dimensional images, and angiography images are presented. A and B: Coronal computed tomography (CT) scan showing pancreatic cancer (yellow arrow) and right renal infarction (orange arrow); C and D: Three-dimensional reconstruction of abdominal CT angiography demonstrating thrombosis of the renal artery, as indicated by orange arrows; E: Right renal artery angiography revealing complete obstruction of the upper and middle branches; F: Post-thrombolysis imaging showing significant improvement in the main and branch vessels of the right renal artery.

FINAL DIAGNOSIS

Based on the rapid onset of severe left-sided abdominal pain and imaging findings revealing a filling defect in the right renal artery, a diagnosis of ARI was made. The radiological findings further strongly supported the diagnosis of pancreatic cancer with liver metastasis. Given that the multiple acute cerebral infarctions could not be explained by vascular distribution, the diagnosis of Trousseau syndrome was established[9].

TREATMENT

Right renal artery angiography was promptly performed. Under high-pressure angiography, the blood flow in the upper and middle branches of the right renal artery was occluded, while the lower branch was well visualized (Figure 2E). Subsequently, intravascular thrombolysis with urokinase was administered. An indwelling contrast catheter was placed postoperatively to allow for intermittent infusion of urokinase and standard heparin over 24 hours. The patient reported relief from abdominal pain (Figure 2F). Following this, we transitioned to subcutaneous administration of low-molecular-weight heparin for anticoagulation. Rechecked D-dimer level was 5.79 mg/L.

OUTCOME AND FOLLOW-UP

We aimed to perform an ultrasound-guided liver or pancreatic biopsy for pathological diagnosis. However, within just two days, the patient developed disorientation, characterized by impaired awareness of the surrounding environment. Magnetic resonance imaging plain scan showed scattered patchy long T1 and long T2 signals in the bilateral lateral ventricles, centrum semiovale and frontoparietal lobes, with high signal on diffusion weighted imaging (DWI) and low signal on apparent diffusion coefficient mapping (Figure 3A-D). Acute cerebral infarction was considered. However, cerebral magnetic resonance angiography showed no significant cerebrovascular stenosis, and the multiple intracranial infarcts could not be explained by the vascular distribution (Figure 3E). Thus, Trousseau syndrome was considered. Only one day later, the patient developed mixed aphasia, central facial paralysis, and right limb weakness. Repeat DWI revealed new infarcts in the bilateral parietal and frontal lobes (Figure 3F). The patient's performance status deteriorated rapidly during this period and only supportive treatment was allowed, with an extremely poor prognosis under palliative care eventually. The patient was discharged due to financial constraints and died of respiratory failure one week later.

Figure 3 Brain magnetic resonance imaging and magnetic resonance angiography images are presented. A-D: Bilateral multiple paraventricular infarctions are demonstrated on T1-weighted images, T2-weighted images, apparent diffusion coefficient mapping, and diffusion-weighted imaging (DWI) sequences; E: Magnetic resonance angiography showing no significant abnormalities; F: Follow-up DWI revealing newly developed infarct lesions in the bilateral parietal and frontal lobes.

DISCUSSION

Patients with pancreatic carcinoma are characterized by a very high risk of thromboembolic disease, a common complication that is causally caused by a tumor-driven procoagulant property. The main clinical consideration of this hypercoagulability has been given to VTE in this population. ATE events tend to present with acute arterial occlusion in specific organs, probably resulting in fatal embolization. The events are usually demonstrated at autopsy, which would certainly tend to underestimate the real incidence. These events mentioned in autopsy studies and several case reports leave challenges in exploring the epidemiology and pathogenesis. Herein, we report a patient with pancreatic cancer presenting ARI as the first sign of the occult malignancy. Our study highlights the marked rarity of acute renal artery occlusion associated with pancreatic cancer and underscores the severity of this complication, which represents a preterminal event.

There is a partial overlap in risk factors for arterial and venous thromboses. It is believed that the generation of a local and systemic hypercoagulable state could confer a growth advantage to tumor cells covered by thrombi, in favor of escaping immune arrestment and promoting growth of metastases. As per the available literature on pancreatic cancer, an episode of ATE correlates with an advanced tumor stage, with a 6-month cumulative incidence of 2.3% at stage 0 compared with 7.7% at stage 4[5]. A retrospective cohort study including 17 patients with pancreatic cancer observed that the time of stroke event always occurs at a metastatic stage[10]. In addition, previous studies have conclusively linked an increased risk of thrombus in association with tumor site in the pancreatic body and tail. In a cohort of patients with pancreatic cancer (n = 202), individuals with a tumor located at corpus/cauda had a 2-fold increased risk compared with those with a tumor located at caput[11]. We made similar observations in this report. Plausible mechanisms for this phenomenon are that tumors of the body and tail are generally larger and more often metastasize at the time of first diagnosis due to delayed specific symptom presentation[12]. More importantly, pancreatic body/tail cancer is associated with the poorly differentiated, molecular squamous subtype and inflammation gene programs, rendering aggressive tumor biology[12,13]. Furthermore, mucinous cystic neoplasms are common in the body or tail. Existing evidence indicates that mucins alone, without thrombin, can activate platelets and generate the microangiopathic form of Trousseau syndrome[13,14]. Unfortunately, a pathological diagnosis could not be performed due to the rapid deterioration of the patient's condition. In addition, plasma CA19-9 serves as an important contributor to pancreatic cancer-associated thrombosis, which may reflect levels of circulating tumor-derived mucin. A prospective cohort study confirmed that patients with extremely high CA19-9 levels developed overwhelming progressive thrombosis and cerebral embolisms[15]. The reason partly lies in the fact that the carcinoma mucin interacts with platelet P-selectin and leukocyte L-selectin to generate platelet-rich microthrombi[16,17]. Thus, in patients with advanced malignancies, tumors located in the pancreatic body or tail, elevated D-dimer levels, and increased CA19-9 levels should be considered predictive indicators for tumor-associated thrombotic events—including Trousseau syndrome—in pancreatic cancer. For individuals exhibiting these clinical features, the sudden onset of visceral pain should prompt clinical suspicion for acute arterial embolism. For instance, abrupt abdominal pain warrants heightened vigilance for acute superior mesenteric artery embolism or acute renal artery embolism, rather than being misattributed solely to neoplastic pain.

The key to the quick diagnosis of ARI lies in enhanced CT, and invasive renal arteriography is pursued as the gold standard for diagnosis. The overall diagnostic and treatment strategies aim to restore TIMI grade 3 blood flow without delay. For ATE, platelet activation appears to be crucial for the development of arterial thrombosis according to Virchow’s triad[18]. However, we must acknowledge that this point was neglected in the therapeutic process. It is worth considering whether both antiplatelet and anticoagulant therapy combinations will attenuate the thrombosis risk and potentially improve long-term outcomes. Furthermore, prior studies pointed out that ATE in pancreatic cancer may be caused by cardiogenic emboli from nonbacterial thrombotic endocarditis or to thrombosis in situ[10]. However, in our study, the patient's condition progressed so rapidly that the source of the thrombus could not be identified without permission for autopsy. In addition, our study was necessarily limited in that a diagnosis with pathology and molecular biology is lacking, which would partly provide evidence to further determine the pathogenesis mechanism and to investigate therapeutic methods and optimal prophylaxis.

CONCLUSION

In summary, we depicted a patient with pancreatic cancer manifesting ARI as the first presentation with a worse outcome, which appears to be a terminal or preterminal event in patients whose disease is initially too far advanced to have any real prognostic value or therapeutic opportunities. To some extent, our report may help raise awareness and promote investigation into prophylactic strategies aimed at preventing this severe complication.

ACKNOWLEDGEMENTS

We appreciate the support from doctors and patients.