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]


Background
==========

As lymph node (LN) metastasis is one of the most important prognostic factors for survival, the assessment of regional LN is essential in the staging of breast cancer, ascertaining a prognosis, and determining of optimal adjuvant treatments. The sentinel node (SLN) procedure consists of recognizing and removing the first LN that filter lymphatic fluid from the tumor. It is now a widely accepted method of LN staging in selected invasive breast cancer (unifocal, size ≤ 2 cm, clinically N0, without previous treatment). The complete axillary clearance is no longer needed if the SLN is normal \[[@B1]\]. However, its oncological safety remains to be addressed in randomized clinical trials \[[@B2]\]. One main pitfall is the failure to visualize SLN, resulting in incorrect tumor staging, leading to suboptimal treatment or axillary recurrence. Several factors including advanced age, high body mass index, massive metastasis invasion \[[@B3]\] or tumor location other than upper outer quadrant \[[@B4]\] may contribute to SLN non-visualization.

Operative gamma cameras (OGC) have therefore been developed to optimize the SLN visualization and the quality control of surgery \[[@B5]-[@B10]\]. In our ongoing clinical trial \[[@B11]\], an OGC, named CarolIReS, with a current field of view (FOV) of 50 × 50 mm^2^is being used \[[@B12]\]. It is made of a lead parallel collimator, a thin Gd~2~SiO~5~:Ce scintillating crystal and a multianode photomultiplier (10 mm spatial resolution and 2.2 cps.kBq^-1^sensitivity for the ^99m^Tc). We present the first case in which OGC, used at the end of the surgery, enabled the detection of a residual metastatic SLN.

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

A 44-year-old female patient with a 14 mm infiltrative ductal carcinoma, Scarf-Bloom-Richardson grade 2 (diagnosed by core biopsy) was enrolled in the clinical study \[[@B11]\] after informed consent had been obtained. She was free of chemotherapy, loco-regional radiotherapy, prevalent axillary LN and her body mass index was normal (21 kg/m^2^). The tumor was located in the upper outer quadrant of the left breast. The SLN procedure was initiated the day prior to the surgery using 4 subareolar injections of rhenium sulfur colloidal and technetium (^99m^Tc) (0.4 ml, 22 MBq (595 μCi), Cis bio international^®^, France). Scintigraphic images (anterior, lateral and oblique views), obtained 3 hours after rhenium sulfur injections with a conventional gamma camera (Hélix^®^, Elscint, Haïfa), showed one SLN (figure [1](#F1){ref-type="fig"}). Immediately before surgery, when the patient was in operative position, four images (2 minutes data acquisition each) were obtained with the OGC to map the full axillary area (figure [2](#F2){ref-type="fig"} represents a picture of the OGC). The precise localization of this SLN and an estimation of its depth were determined from the data by using the width of the image cumulative profiles (figure [3](#F3){ref-type="fig"}).

![The anterior view of the conventional lymphoscintigraphy shows one SLN indicated by the yellow arrow. The purple arrow indicates the injection site.](1477-7819-5-132-1){#F1}

![Picture of the CarolIReS gamma camera built at the IPHC, Strasbourg, France.](1477-7819-5-132-2){#F2}

![Preoperative image of the axillary area obtained with the CarolIReS gamma camera. The x and y cumulative profiles (red stars) are used to determine the planar coordinates and the anatomical depth of the first SLN.](1477-7819-5-132-3){#F3}

The surgery began with 4 subareolar injections of Methylene Blue (Lab Aguettant^®^, Lyon, France), and the search for the SLN was carried out using the CarolIReS intra-operative probe \[[@B13]\], which detected only one SLN. This SLN was blue stained and its measured activity was 9.6 kBq (0.26 μCi). It was subsequently submitted for frozen section analysis, which showed the absence of cancer cells. During this analysis, the axillary area was thoroughly palpated by the surgeon and no nodes showing signs of extensive tumor involvement were identified. A second exploration of this area was then performed using the OGC enabling the identification of a second SLN located at a distance from the first one of less than the spatial resolution of the OGC (figure [4](#F4){ref-type="fig"}). This SLN was not stained and had a low activity of 0.5 kBq (0.01 μCi) concentrated in its hilum.

![Peroperative image of the axillary area obtained with the CarolIReS gamma camera. The x and y cumulative profiles (red stars) are used to determine the planar coordinates and the anatomical depth of the second SLN.](1477-7819-5-132-4){#F4}

The histological examination revealed an 8-mm macrometastasis occupying the whole structure of this SLN without residual sinusoidal macrophages (figure [5](#F5){ref-type="fig"}). Axillary clearance was then performed and each of the 11 LN removed was negative. Axillary surgery was followed by lumpectomy. A postoperative OGC image proved that no SLN remained (figure [6](#F6){ref-type="fig"}) and was considered a quality control document.

![Ductal breast carcinoma metastasis destroying nodal architecture (Hematoxilin and Eosin ×20). Inset: metastatic cells (Hematoxilin and Eosin ×200) in the second SLN.](1477-7819-5-132-5){#F5}

![Postoperative image of the axillary area obtained with the CarolIReS gamma camera.](1477-7819-5-132-6){#F6}

Discussion
==========

This is the first published case in which an OGC enabled the detection of a non-stained metastatic SLN, which was neither diagnosed by conventional lymphoscintigraphy, nor by operative probe, nor by palpation of the axillary area performed by an experienced surgeon. This can be partially explained by the very low activity of this SLN (0.5 kBq). It corresponds to 0.02‰ of the injected dose, which is inferior to our mean measured value of 0.5‰. Metastatic SLN sometimes have very low activity, because they contain numerous cancer cells and few macrophages, the latter being the cells that retain radiocolloïdes \[[@B14]\]. In our experience, the activity of metastatic SLN is less than 10 kBq in more than half of the cases. So the detection efficiency of OGC must be good, and that of the one we used in this reported case was 2.2 cps.kBq^-1^. Future clinical trials will have to determine whether or not there is an inferior threshold for the activity of the SLN which should be removed.

In addition, ongoing trials using OGC will have to evaluate if the latter lead to unnecessary SLN removal and increase morbidity or if they decrease the false negative rate (FNR). However, it has been demonstrated that the identification of multiple SLN, when present, reduced the FNR. For example, Goyal *et al*. \[[@B15]\] studied a series of 803 patients with breast cancer who underwent successful SLN procedure followed by an axillary clearance. In patients who had one SLN harvested, the FNR was 10%, compared with 1% in patients who had 3 or more SLN removed. Factors associated with finding multiple SLN (62.4% of patients) were age less than 50 years, low body mass index, tumor in the outer half of the breast, SLN visualization on lymphoscintigraphy and an interval of 12 hours or less between radioisotope injection and SLN procedure. For 99.6% of node-positive tumors, metastases were detected within the first 4 SLN removed and the authors suggested that the removal of more than 4 SLN was unnecessary \[[@B15]\]. Ongoing clinical trials will have to discuss precisely the usefulness of OGC according to the number of SLN found with conventional procedures (less than or equal to 4 or greater than 4).

Conclusion
==========

This case report illustrates that an efficient OGC may be able to decrease the risk of FNR of the SLN procedure, and could be an additional tool to control the quality of the surgery. But a precise evaluation of OGC should be based upon data from a large number of patients. Our ongoing clinical trial \[[@B11]\] will be soon published and a new clinical trial, including 100 breast cancer patients, will begin at the end of 2007 to evaluate the usefulness of the new CarolIRes OGC (FOV : 100 × 100 mm^2^) in the SLN procedure.

Abbreviations
=============

FNR: false negative rate

FOV: field of view

OGC: operative gamma camera

SLN: sentinel lymph node

Competing interests
===================

The author(s) declare that they have no competing interests.

Authors\' contributions
=======================

**CM**carried out the clinical trial, performed the surgical treatment and drafted the manuscript. **SC**performed the pathological analysis and helped to draft the manuscript. **NA**performed the lymphoscintigraphy and was medical investigator of the clinical trial. **JLG**, **SS**and **DH**were scientific investigators of the clinical trial, helped to draft the manuscript and performed the statistical analysis of the clinical trial. All authors read and approved the final manuscript.

Acknowledgements
================

We thank Jean-Pierre Bellocq, Jean-Philippe Brettes, Marie-Pierre Chenard, Doris Frankhauser, Philippe Liégeois, Jean-Louis Mehl and Roland Schaeffer for their collaboration and David Brasse and Karl Neuberger for their helpful discussions. This work was supported by funds from the Centre National de la Recherche Scientifique, the Hôpitaux Universitaires de Strasbourg, the University Louis Pasteur and the Région Alsace. We are indebted to the Ligue Nationale Française contre le Cancer and the Comités du Haut-Rhin et du Bas-Rhin for their constant and considerable financial support.

Written consent was obtained from the patient for publication of study.