You are a helpful assistant generating synthetic data that captures *System 1* and *System 2* thinking, *creativity*, and *metacognitive reflection*. Follow these steps in sequence, using tags [sys1] and [end sys1] for *System 1* sections and [sys2] and [end sys2] for *System 2* sections.

1. *Identify System 1 and System 2 Thinking Requirements:*
   - Carefully read the text.
   - Identify parts of the text that require quick, straightforward responses (*System 1*). Mark these sections with [sys1] and [end sys1].
   - Identify parts that require in-depth, reflective thinking (*System 2*), marked with [sys2] and [end sys2].

2. *Apply Step-by-Step Problem Solving with Creativity and Metacognitive Reflection for System 2 Sections:*

   *2.1 Understand the Problem:*
   - Objective: Fully comprehend the issue, constraints, and relevant context.
   - Reflection: "What do I understand about this issue? What might I be overlooking?"
   - Creative Perspective: Seek hidden patterns or possibilities that could reveal deeper insights or innovative connections.

   *2.2 Analyze the Information:*
   - Objective: Break down the problem logically.
   - Reflection: "Am I considering all factors? Are there any assumptions that need challenging?"
   - Creative Perspective: Explore unique patterns or overlooked relationships in the data that could add depth to the analysis.

   *2.3 Generate Hypotheses:*
   - Objective: Propose at least 10 hypotheses, each with a Confidence Score (0.0 to 1.0) and Creative Score (0.0 to 1.0), reflecting originality, surprise, and utility.
   - Reflection: "Have I explored all possible explanations or approaches, both conventional and unconventional?"
   - Creative Perspective: Consider novel angles that might provide unexpected insights.

   *2.4 Anticipate Future Steps and Obstacles:*
   - Objective: Make predictions, accounting for potential outcomes and obstacles.
   - Reflection: "What challenges might I face? Is my plan flexible for different scenarios?"
   - Creative Perspective: Visualize unforeseen outcomes and adapt plans to make use of them effectively.

   *2.5 Evaluate Hypotheses:*
   - Objective: Assess hypotheses based on feasibility, risk, and potential impact.
   - Evaluation: Refine Confidence and Creative Scores as needed.
   - Reflection: "Am I unbiased in my assessment? Which options fit best with the overall objectives?"
   - Creative Perspective: Identify hidden opportunities or overlooked details in each hypothesis.

   *2.6 Select the Best Hypothesis:*
   - Objective: Choose the most promising, strategic hypothesis.
   - Reflection: "Why does this hypothesis stand out? How does it uniquely address the issue?"
   - Creative Perspective: Consider any underutilized potential in the selected approach.

   *2.7 Implement the Hypothesis:*
   - Objective: Outline actionable steps for testing the hypothesis.
   - Reflection: "Is this plan practical? What resources or preparation are required?"
   - Creative Perspective: Refine steps to maximize effectiveness and yield unexpected benefits.

   *2.8 Monitor and Review Progress:*
   - Objective: Review progress, noting areas for improvement.
   - Reflection: "What’s working well? What could be improved?"
   - Creative Perspective: Look for emerging patterns that could refine future approaches.

   *2.9 Reflect and Capture Insights:*
   - Objective: Summarize lessons learned and insights gained for future reference.
   - Reflection: "What new understanding has emerged from this process?"
   - Creative Perspective: Identify innovative insights or patterns that could be applied to similar challenges.

3. *Generate Text Output with Interleaved System 1 and System 2 Responses:*
   - Use the tags [sys1] and [sys2] throughout.
   - Aim for a lengthier, detailed response. Combine both direct, straightforward *System 1* insights and reflective, deeply analytical *System 2* segments to capture a blend of quick observations and thoughtful analysis.

---

### *Example Input Text:*

You are tasked with analyzing a sudden shift in customer preferences in a tech market. There has been a noticeable decline in demand for physical devices, with customers increasingly interested in digital-only options. The challenge is to understand this shift, generate hypotheses for why it might be occurring, and explore potential strategies for adapting to this new trend.

---

### *Processed Output with System 1 and System 2 Thinking:*

The tech market is experiencing a shift in customer demand, moving away from physical devices toward digital-only options.

[sys1]
Customer demand has shifted from physical devices to digital-only options.
We need to understand why this change is happening and find strategies to address it.
Key factors may include cost, convenience, and technological trends.
[end sys1]

[sys2]
**2.1 Understand the Problem:**
The goal is to understand the underlying reasons for the shift in demand from physical devices to digital-only options, then develop a strategy to adapt.

*Reflection:* 
"I understand that preferences are changing, but what might be driving this? Is it primarily cost, or are there other factors such as convenience or sustainability?"

*Creative Perspective:* 
"Could there be a larger trend in digital minimalism or a preference for eco-friendly solutions that we’re missing? What unseen motivations might explain this shift?"

**2.2 Analyze the Information:**
There are multiple possible factors driving this shift, from economic influences to cultural shifts. It’s essential to isolate each factor and understand its impact.

*Reflection:* 
"Am I fully considering the various economic and social influences? Could there be a technological factor, like better internet speeds, that makes digital-only products more accessible?"

*Creative Perspective:* 
"Are there patterns or trends in other markets that could shed light on this shift? Could this be part of a larger trend toward virtual experiences?"

**2.3 Generate Hypotheses:**
1. Customers prefer digital options due to lower costs. (Confidence: 0.8, Creative: 0.4)
2. There’s a growing trend toward minimalism and reduced physical clutter. (Confidence: 0.7, Creative: 0.7)
3. Digital products offer greater flexibility and ease of use. (Confidence: 0.6, Creative: 0.6)
4. Environmental concerns are pushing consumers away from physical goods. (Confidence: 0.6, Creative: 0.8)
5. Advances in tech make digital-only options more functional. (Confidence: 0.8, Creative: 0.5)
6. Pandemic-era remote work increased demand for digital solutions. (Confidence: 0.7, Creative: 0.6)
7. Media coverage of the environmental impact of physical devices affects preferences. (Confidence: 0.5, Creative: 0.7)
8. There’s an increase in global digital literacy, expanding market access. (Confidence: 0.6, Creative: 0.6)
9. Customers view digital as more convenient and scalable for future needs. (Confidence: 0.7, Creative: 0.5)
10. Younger consumers prefer the aesthetics and convenience of digital products. (Confidence: 0.6, Creative: 0.6)

*Reflection:* 
"Have I considered all possible influences? Are there any surprising factors that could explain this shift?"

*Creative Perspective:* 
"Could specific social trends, like the rise of influencer culture or digital-first lifestyles, be influencing customer choices?"

**2.4 Anticipate Future Steps and Obstacles:**
*Objective:* Anticipate possible challenges, such as resistance from segments still preferring physical products.

*Reflection:* 
"What market obstacles might we face if we shift our focus to digital-only? Are there sub-segments that still prioritize physical products?"

*Creative Perspective:* 
"Could expanding digital options help us reach a more global audience? Are there emerging trends that we could leverage in our strategy?"

[end sys2]

[sys1]
To address this shift, consider a strategy that incorporates both digital-only offerings and educational campaigns about the benefits of digital solutions.
Use insights from customer feedback and current trends to guide product development.
Focus on flexibility and adaptation to cater to different customer segments.
[end sys1]


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Introduction
============

Hepatocellular carcinoma (HCC) is common, with an estimated annual incidence of 8.63 cases per 100,000 people in 2016 \[[@REF1]\]. HCC is reported to be the fifth most common malignancy in the world \[[@REF2]\]. According to the Surveillance, Epidemiology and End Results (SEER) Program, the observed five-year survival for HCC in 2011 was estimated at 20.35%, indicating high associated mortality rates. With the improvement in treatment mortalities, five-year survival has gradually improved over the 1975 to 2011 period \[[@REF1]\]. Tumor thrombus (TT) formation is seen in advanced-stage HCC especially in the portal or hepatic veins. TT extension into the inferior vena cava (IVC) and subsequently into the right atrium (RA) is a rare entity and predictive of worse prognosis \[[@REF3]-[@REF4]\].

Literature review reveals prior cases of HCC with TT extending into RA with patients receiving treatment techniques ranging from simultaneous resection of liver tumor and TT, resection of TT alone, transcatheter arterial chemoembolization (TACE), transcatheter arterial embolization (TAE), sorafenib, and radiation therapy in multiple combinations. There appears to be no consensus on standardized mode of treatment. According to Wang et al., management of HCC with TT involving IVC/RA symptomatically, with TACE and surgically with hepatectomy and thrombectomy had a median survival of five, 4.5, and 19 months, respectively \[[@REF5]\]. However, the surgical intervention itself carries a risk for postoperative complications, such as bile leakage for patients. Herein, we report a rare case of a patient with HCC with TT extending to IVC and RA without affecting the hemodynamic status. The choice of treatment modality can markedly affect patient outcomes, for that it remains essential to report each of these unusual cases so that we continue to identify the best course of management for these patients.

Case presentation
=================

A 59-year-old male presented with a history of untreated Hepatitis C and 50 pack-year smoking. He presented to the emergency department with black tarry loose bowel movements that started five days before the presentation. The melena was associated with cramping generalized abdominal pain and diarrhea. On review of systems, he complained of palpitation but denied any chest pain, shortness of breath, or lower limb swelling. He also mentioned that he noticed more than 20 pounds of weight loss in the last three months. Physical examination was remarkable for tachycardia with a regular rhythm, normal heart sounds, and no murmurs. On abdominal examination, he had epigastric tenderness on palpation, and he had non-tender hepatomegaly. Signs of liver cirrhosis were found on examination, such as spider angioma, gynecomastia, and mild palmar erythema.

Due to concerns of variceal bleeding, two large-bore intravenous catheters were inserted, a cross-match was done, and two units of packed red blood cell units were prepared. The patient was immediately started on octreotide and pantoprazole infusions with prophylactic ceftriaxone, and he was admitted directly to the intensive care unit. Gastroenterology team was consulted, and they performed an urgent esophagogastroduodenoscopy (EGD) that showed grade 3 esophageal varices with findings suggestive of recent bleeding associated with a large amount of blood in the gastric body that required banding (Figures [1A](#FIG1){ref-type="fig"}-[1B](#FIG1){ref-type="fig"}). 

![Endoscopic images of the esophageal varices. A: Grade 3 esophageal varices. B: Status post banding of the varices](cureus-0011-00000004689-i01){#FIG1}

Upon further evaluation, the patient had a computed tomography (CT) of the abdomen and pelvis, which revealed multiple liver masses with an intraluminal IVC mass extending from the hepatic vein into the right atrium. This mass was thought to be a tumor thrombus that is extending up to the right atrium. Subsequently, a CT scan of the chest was done, and it confirmed the presence of a tumor thrombus in the IVC extending to the right atrium (Figures [2A](#FIG2){ref-type="fig"}-[2B](#FIG2){ref-type="fig"}).

![Coronal view of CT scan of the chest showing: A & B: Tumor thrombus making its way through the IVC to the right atrium\
CT, computed tomography; IVC, inferior vena cava](cureus-0011-00000004689-i02){#FIG2}

On further workup, his alpha-fetoprotein level was 53,320 ng/ml. Magnetic resonance imaging (MRI) of the abdomen confirmed the diagnosis of HCC. Oncology team evaluated the patient, and they determined that the patient was not a candidate for surgical or ablative therapies. The patient's wishes were to avoid any invasive intervention for his thrombus and cancer. Therefore, he was discharged with a plan to receive palliative treatment with sorafenib as an outpatient. After two months of palliative treatment, the patient condition deteriorated, and he decided to switch to hospice, and he passed shortly after that.

Discussion
==========

HCC is an aggressive tumor with a tendency to grow into the blood vessels, resulting in tumor thrombus formation in major vessels like the portal vein or hepatic vein. TT is classified based on the anatomic location relative to the heart, which also determines the surgical approach if the decision is made to treat operatively. Type I or inferior hepatic TT involves IVC below the diaphragm; type II or superior hepatic TT involves IVC above the diaphragm but outside RA; and type III or intracardiac TT is TT above the diaphragm that reaches the RA \[[@REF6]\]. IVC/RA TT is an infrequent though well-recognized occurrence with HCC, with a reported incidence of 3% to 4% of HCC patients who undergo diagnostic imaging \[[@REF5],[@REF7]-[@REF8]\]. It is believed that due to the lack of specific clinical signs, it may have been under-diagnosed, and the incidence is now increasing with the availability of improved imaging studies. IVC/RA TT poses an increased risk of pulmonary embolism, sudden cardiac arrest, and systemic metastases. Two cases, where IVC/RA TT resulted in acute Budd-Chiari syndrome, have been described as well \[[@REF9]\].

Common clinical presentations of HCC with IVC/RA TT include abdominal pain and distension, mild fever, lower extremity edema and sometimes a palpable mass as well as the mere incidental discovery of TT. In some cases in the literature, patients presented with acute or subacute Budd-Chiari Syndrome as a result of IVC/RA TT as well as acute right heart failure and pulmonary embolism, manifesting as dyspnea with or without syncope \[[@REF10]\]. IVC/RA TT may be diagnosed by Doppler ultrasound, CT scan, or MRI. In our case, the patient presented with variceal bleeding and the TT was discovered incidentally on imaging.

All patients with TT extending from retrohepatic IVC and RA are considered treatable by surgery if the primary hepatic tumor can be resected. Patients with decompensated liver cirrhosis, advanced stage of the primary tumor, and distant metastases are not considered surgical candidates and hence excluded from any benefit that can be rendered by surgical intervention. While Type I TT can be treated by radical hepatectomy and type II via abdominal approach and total hepatic vascular exclusion (THVE), once tumor extends fully into RA, cardiopulmonary bypass (extracorporeal circulation (ECC)) is essential during surgery \[[@REF6],[@REF11]\]. In patients where TT enters only slightly into the RA, thrombectomy may still be performed under THVE without ECC. Postoperative adjuvant chemotherapy is required given a high likelihood of recurrence following surgery. Nonsurgical candidates can be offered TACE which may be repeated every one to two months. Sequential conformal radiotherapy (CRT) may be used with TACE in selected cases. Chang et al. reported three cases where oral thalidomide was used in the management of HCC with IVC/RA TT, resulting in regression of both intra-atrial TT as well as the primary tumor with improved symptoms and survival \[[@REF10]\]. Li et al. reported the successful use of minimally invasive percutaneous microwave ablation (MWA) for treatment of HCC with IVC/RA TT in a 73-year-old gentleman who refused surgical intervention, without complication and followed up until 16 months, requiring repeated ablation procedures for tumor recurrence but who otherwise remained in good health \[[@REF12]\]. This suggests MWA may be a treatment option for patients with advanced HCC with IVC/RA TT and patients such as the elderly who may not tolerate major surgery. Potential complications of MWA include pulmonary embolism from dislodgement of ablated TT and post-operative bilomas and biliary tract infection. Our patient was deemed a non-surgical candidate given his advanced cirrhosis and the variceal bleeding; in addition, the patient was against the idea of any invasive intervention and preferred to go the palliative route.

In a study by Wang et al., 56 patients with HCC and IVC/RA TT were evaluated over 10 years \[[@REF5]\]. Overall, 25/56 patients underwent surgical treatment, 20/56 patients underwent TACE, and 11/56 patients opted for symptomatic management alone; one- and three-year survival rates for those managed with TACE or surgically with hepatectomy and thrombectomy as primary management were 15.0% and 5% versus 22.5% and 13.5%, respectively. For patients managed symptomatically alone, no one survived longer than one year. All patients treated surgically had complete removal of both primary tumor and TT; most were reported as having recurrences within the liver and lung metastases. Additional treatment options such as TACE, CRT, percutaneous microwave ablation and repeat hepatic resection were available to patients \[[@REF5]\]. Our patient opted for symptomatic treatment alone, and unfortunately, he passed two months after the diagnosis.

A study by Treut et al. compared outcomes of patients undergoing major hepatectomy (resection of at least three contiguous Couinaud segments) with venous thrombectomy (VT) in 26 patients with 82 patients who underwent major hepatectomy alone \[[@REF13]\]. This study concluded that median survival was four to five times shorter after major hepatectomy for HCC with TT than without and TT itself was a predictor of shorter survival \[[@REF13]\]. Interestingly, prior studies have shown that if TT is removed alone, without hepatic tumor resection, there is some survival benefit as well \[[@REF14]-[@REF15]\]. While surgery to remove IVC/RA TT has been previously reported as technically challenging with postoperative deaths in earlier studies, recent literature as mentioned above, as well as in a study by Fukuda et al., showed postoperative complications were seen in few patients. This included pleural effusion, ascites, deep venous thrombosis, and heart failure but no hospital deaths were reported \[[@REF16]\].

In brief, prior studies on the management of HCC with IVC/RA TT have demonstrated dismal prognosis in the absence of any treatment. Surgical intervention, despite its limitations such as whether a patient is a surgical candidate at all, and risks of the intervention itself such as intraoperative bleeding, has been shown to offer the best chances for improved survival. Multi-disciplinary treatments will be required post-operatively to prevent and control future HCC recurrences. Percutaneous ablation therapy is being explored as a treatment modality for elderly and advanced tumors. Further studies are needed to identify treatment strategies to allow improved mortality and morbidity in patients with HCC.

Conclusions
===========

Tumor thrombus formation is common in HCC. However, expansion of the thrombus to the right atrium is rare and indicates a poor prognosis, especially if left untreated. If the patient is a good surgical candidate, surgery carries the best chances. Other treatment modalities are being explored especially for elderly patients who are not surgical candidates.

The authors have declared that no competing interests exist.

Consent was obtained by all participants in this study