Probe - Based Confocal Endomicroscopy and Endoscopy in NBI Module - The Role in Clinical Decision - Case Reports

Abstract

Cancer remains a significant global cause of mortality, irrespective of a country's level of development. Among all cancer types, gastrointestinal cancers claim the highest number of lives annually. This disease predominantly affects individuals in their 6th to 8th decades of life. Unfortunately, diagnoses often occur during advanced stages of the illness, rendering chemotherapy less effective and offering a reserved prognosis. Conventional endoscopy, however, struggles to differentiate lesions based on their histological composition. Consequently, the management of patients largely depends on histopathological examinations, which can be time-consuming. Biopsy results are sometimes delayed, with precious weeks passing, particularly critical for patients with malignant lesions. Moreover, biopsies may yield inconclusive results if not precisely targeted, leading to potential mismanagement, unnecessary resections and burdensome pathology services. This series of cases underscores, as previous studies have, the value of modern endoscopic techniques in determining the appropriate therapeutic approach for each patient, an approach that ensures the highest quality of life.

Introduction

Cancer remains a significant global cause of mortality, irrespective of a country's level of development.

Among all cancer types, gastrointestinal cancers claim the highest number of lives annually [1].

This disease predominantly affects individuals in their 6th to 8th decades of life [2].

Unfortunately, diagnoses often occur during advanced stages of the illness, rendering chemotherapy less effective and offering a reserved prognosis [3].

This situation stems from multiple factors, including the absence of widespread screening programs, their associated costs, malnutrition, increased exposure to toxic substances, and lifestyle choices, among others.

A primary focus of gastroenterological and oncological research is the development of innovative methods for early detection of premalignant and malignant lesions, and their subsequent treatment, providing substantial benefits to patients and cost-effectiveness.

Only a handful of countries have successfully implemented serious screening initiatives to combat digestive tract cancers.

In contrast, Romania primarily relies on opportunistic screening, typically diagnosing preneoplastic or malignant lesions while investigating other pathologies or syndromes.

Conventional endoscopy, however, struggles to differentiate lesions based on their histological composition.

Consequently, the management of patients largely depends on histopathological examinations, which can be time-consuming [4, 5, 6, 7, 8].

Biopsy results are sometimes delayed, with precious weeks passing, particularly critical for patients with malignant lesions.

Moreover, biopsies may yield inconclusive results if not precisely targeted, leading to potential mismanagement, unnecessary resections, and burdensome pathology services.

A significant portion of digestive tract cases originate from preneoplastic lesions, frequently managed inadequately due to insufficient understanding of their histopathological characteristics and malignant potential.

This prompted the development of novel endoscopic techniques capable of providing true "optical biopsies" by analyzing mucosal patterns, intra- and perilesional vessels, and even visualizing lesions at the cellular level.

Narrow band imaging (NBI) endoscopy and probe-based confocal laser confocal endomicroscopy (pCLE) have emerged as alternative diagnostic tools for preneoplastic lesions in both the upper and lower digestive tract.

However, the accessibility of these two methods differs significantly.

While virtual chromoendoscopy, a component of many new endoscopes, is readily available with a simple button press and at no additional cost, endomicroscopy remains inaccessible to many healthcare centers due to the high cost of equipment and consumables.

Aim

This study tries to assess the efficacy of the two previously mentioned techniques, endoscopy with narrow band imaging (NBI) and probe-based confocal laser confocal endomicroscopy (pCLE).

Our primary objectives encompass the evaluation of these methods regarding their ability to diagnose preneoplastic lesions and to detect malignancies at an early stage.

For this, we chose 3 patients with large colonic polyps in which the resection margins were evaluated by endomicroscopy to determine whether endoscopic resection is sufficient or surgical treatment is required.

Looking ahead, our future endeavors will involve exploring the feasibility of establishing an instant histological diagnostic algorithm.

This algorithm would rely on the computerized analysis of the images obtained through these diagnostic methods, potentially streamlining and enhancing the diagnostic process.

Case presentations

Case 1

The first case is that of a 78-year-old patient, hypertensive, receiving proper cardiac treatment at home, without any other significant personal or family medical history.

The patient presented to the emergency department with the complaint of passing multiple stools containing fresh red blood and significant physical fatigue.

The physical examination did not reveal significant changes.

Paraclinical investigations showed a severe anemic syndrome, with a hemoglobin level of approximately 7g/dl and low erythrocyte indices.

A lower gastrointestinal endoscopy, performed after appropriate preparation, revealed, at approximately 30cm from the external anal opening, two polyps (Figure 1).

Figure 1.

Classic examination in white light

One of them was sessile (PARIS Type Is), measuring approximately 15mm, with an irregular pit-pattern (NICE 3), centrally depressed.

The other was semi-pedunculated (PARIS Type Isp), measuring approximately 30mm, with an irregular pit-pattern (NICE 2-3), both showing minimal bleeding at the time of examination (Figure 2).

Figure 2.

NICE 3 polip - endoscopic examination in NBI module

It was decided to resect both polyps.

Both polyps exhibited proper elevation after the injection of a saline solution into the submucosa.

After resection, the semi-pedunculated polyp showed suggestive signs of submucosal invasion.

Following the patient's informed consent, intravenous injection of 5% sodium fluorescein was administered, and the resection margins and resection defect were examined by endomicroscopy, revealing no anomalies in crypts, vascular networks, or inflammatory infiltrates (Figure 3).

Figure 3.

Normal aspect of the colonic mucosa - images obtained by pCLE after evaluation of resection margins

The resected specimens were sent to the Pathology Department, and the results indicated clear resection margins.

A follow-up colonoscopy performed after 3 months revealed normal post-polypectomy scarring (Figure 4).

Figure 4.

Post-polypectomy scar of normal appearance (examination under white light).

Case 2

The next case involves a 57-year-old man with no significant personal or family medical history who presented to the hospital for evaluation of chronic diarrhea syndrome.

The physical examination and laboratory investigations did not reveal significant changes. Inflammatory markers were also within normal limits.

A decision was made to perform a colonoscopy, which revealed, at approximately 10cm in the rectum, a sessile polyp (Paris type Is) with multiple lobes (Figure 5), measuring approximately 3cm and a wide base of attachment.

Figure 5.

Classic examination in white light

During the endoscopic examination in NBI mode, areas with profoundly disorganized vascular architecture were observed, indicative of submucosal invasion (Figure 6).

Figure 6.

NICE 2-3 polip - endoscopic examination in NBI module

A decision was made to perform pCLE examination to determine the appropriate treatment course, including the potential need for surgery.

After injecting the contrast agent (5% sodium fluorescein), the examination started approximately 2 minutes later.

The findings revealed disorganized crypt architecture, significant vascular proliferation, and inflammatory infiltrate (Figure 7).

Figure 7.

Disorganized crypt architecture, significant vascular proliferation, and inflammatory infiltrate - adenocarcinoma in pCLE examination

These aspects were suggestive of adenocarcinoma, leading to the transfer of the patient to the surgery for radical treatment.

To further demonstrate the value of the aforementioned examinations, attempts were made to inject the polyp with saline solution into the submucosa, but satisfactory elevation was not achieved (Figure 8).

Figure 8.

Appearance after injection of saline solution into the submucosa

Surgical intervention was performed and the histopathological examination revealed a malignant polyp (with deep submucosal invasion) and angiolymphatic invasion.

Case 3

This is the case of a 67-year-old man who underwent surgery for left bronchopulmonary neoplasm approximately 10 years ago.

He was also diagnosed and underwent surgery for sigmoid adenocarcinoma about 5 years ago.

However, he has not undergone annual follow-up colonoscopy examinations after the surgical interventions.

He was referred from the outpatient clinic to the surgical clinic for the surgical resection of a large-sized laterally spreading flat polyp.

A colonoscopy was performed again to assess the possibility of endoscopic resection, revealing a mixed type LST-G flat polyp, approximately 4cm in size (Figure 9).

Figure 9.

LST - G mixed nodular type (0 - IIa + Is) - classic examination in white light.

The endoscopic examination in NBI mode revealed a characteristic image of a villous adenoma with a regular vascular pit-pattern and no areas of disorganized architecture (Figure 10).

Figure 10.

LST - G mixed nodular type (0 - IIa + Is) NICE 2 - endoscopic examination in NBI module

The polyp was also examined with pCLE which showed thickened, mildly irregular epithelium with a villiform appearance, suggestive of a villous adenoma with low-grade dysplasia (Figure 11).

Figure 11.

Dark, irregularly thickened epithelium and viliform structure - appearance of a vilous adenoma with low-grade dysplasia in pCLE examination

As a result, the surgical intervention for which the patient was referred to our center was deemed unnecessary.

The polyp was endoscopically resected by piece-meal mucosectomy.

The histopathological examination of the resected specimen confirmed the findings obtained at endomicroscopy.

Discussions

This series of cases underscores, as previous studies have, the value of modern endoscopic techniques in determining the appropriate therapeutic approach for each patient, an approach that ensures the highest quality of life [1].

Another aspect that cannot be overlooked is the cost-effectiveness of therapeutic methods used in the treatment of preneoplastic lesions of the digestive tract [7].

As seen in the third case, the therapeutic approach was radically changed after reexamining the lesion through virtual chromoendoscopy and endomicroscopy.

Hence, the need for young endoscopists to use these new endoscopic techniques on a much broader scale is revisited, as they are readily available at the push of a button, and the learning curve is not steep [6, 7, 8].

Regarding availability, the advantage of NBI endoscopy over endomicroscopy is evident.

The costs associated with endomicroscopy remain consistently high, both in terms of equipment acquisition and consumables, which currently limits its use in Romania primarily to research purposes.

Conclusions

We can affirm that new endoscopic techniques, especially NBI (Narrow Band Imaging) endoscopy, currently play a significant role in the management of patients with preneoplastic lesions.

This technique is accessible, and the learning curve is not lengthy.

Furthermore, training young endoscopists in the use of these new technologies is imperative to ensure optimal treatment and cost optimization.

Equally important is the implementation of national screening programs in the near future, at least for the lower digestive tract.

Conflict of interests

None to declare.

Source of funding

This work was supported by the grant POCU/993/6/13/153178, ”Performanță în cercetare” - "Research performance" co-financed by the European Social Fund within the Sectorial Operational Program Human Capital 2014-2020.