Endoscopic diagnosis and management of gallbladder carcinoma in minimally invasive era: New needs, new models

Abstract

Gallbladder cancer (GBC) is a rare and lethal malignancy; however, it represents the most common type of biliary tract cancer. Patients with GBC are often diagnosed at an advanced stage, thus, unfortunately, losing the opportunity for curative surgical intervention. This situation leads to lower quality of life and higher mortality rates. In recent years, the rapid development of endoscopic equipment and techniques has provided new avenues and possibilities for the early and minimally invasive diagnosis and treatment of GBC. This editorial comments on the article by Pavlidis et al. Building upon their work, we explore the new needs and corresponding models for managing GBC from the endoscopic diagnosis and treatment perspective.

Key Words: Endoscopy; Diagnosis and treatment; Gallbladder carcinoma; Minimal invasive; New need; New model

Core Tip: Gallbladder cancer (GBC) poses a significant challenge due to its low rates of early diagnosis and high mortality. The evolving endoscopic technologies in the minimally invasive era present new possibilities for the early diagnosis and treatment of GBC, making them highly research-worthy and promising for application. The promotion and application of advanced endoscopic equipment and techniques, such as endoscopic ultrasound, magnifying endoscopy, choledochoscopy, confocal laser endomicroscopy, and natural orifice transluminal endoscopic surgery technology, are expected to offer new management models for the global demand in GBC diagnosis and treatment.

INTRODUCTION

Despite being relatively rare, gallbladder cancer (GBC) is the most common malignancy of the biliary tract and is globally recognized for its poor prognosis[1,2]. Recent studies have found relatively higher GBC mortality rates in countries with medium human development index and high-income Asia-Pacific regions[1,3]. Additionally, there has been a rising trend in GBC mortality after an initial decline in some high-income countries[4].

Although regional and demographic variations in GBC are pronounced, the global burden of this cancer is expected to rise considerably in the next two decades, a trend that merits serious attention and contemplation[3,5]. The poor treatment outcomes for GBC patients are not mainly due to inadequate surgical techniques or the absence of therapeutic modalities such as chemotherapy, immunotherapy, targeted therapy, and radiotherapy. The primary issue lies in the low rate of early diagnosis of GBC, which results in futile attempts at various treatment modalities at an advanced cancer stage. From this perspective, the most cost-effective approach to improving GBC patients’ five-year survival rate and quality of life (QoL) would be early diagnosis followed by subsequent minimally invasive treatment. Advanced endoscopic equipment and techniques with rapid developments in recent years, such as endoscopic ultrasound (EUS), magnifying endoscopy, choledochoscopy, confocal laser endomicroscopy (CLE), and natural orifice transluminal endoscopic surgery (NOTES) technology, offer new possibilities for achieving the abovementioned objectives[6]. We are very interested in the review by Pavlidis et al[7] published in a recent issue of World Journal of Gastrointestinal Oncology. In the ever-evolving landscape of digestive oncology, this enlightening review reiterates the emerging trends in diagnosing and treating GBC. We thank Pavlidis et al[7] for their review, which has raised attention to new trends in diagnosing and treating GBC.

ENDOSCOPIC DIAGNOSIS AND MANAGEMENT

Reference Citation Analysis (RCA, https://www.referencecitationanalysis.com/) is a unique artificial intelligence system for citation evaluation of biomedical literature. RCA has been employed to analyze previous studies of GBC’s endoscopic diagnosis and management to April 2024. Published research in this field primarily focuses on early endoscopic diagnosis and its comparison with traditional examinations, palliative endoscopic treatment for advanced-stage patients, and minimally invasive endoscopic surgery for gallbladder diseases.

First, early diagnosis of GBC is paramount for improving patients’ far-from-ideal five-year survival rates and QoL. However, preoperative diagnosis of neoplastic gallbladder polyps and gallbladder wall thickening remains a challenge, and the application value of a 1 cm threshold as a surgical indication for cholecystectomy in gallbladder polyps has also been questioned[8]. Despite the availability of various diagnostic methods for GBC, such as abdominal ultrasound, computed tomography, magnetic resonance imaging, positron emission tomography computed tomography, or 18F-FDG positron emission tomography-magnetic resonance imaging, it is regrettable that these methods have not significantly improved the early detection rate of GBC. Compared to these methods, as Pavlidis et al[7] mentioned, endoscopic techniques enable pathological diagnosis of GBC. Moreover, current endoscopic techniques allow visualization of lesions inside the gallbladder, facilitating targeted biopsies such as EUS-guided fine needle aspiration/fine needle biopsy to obtain cancer cells for pathological confirmation, thereby definitively diagnosing GBC and improving accuracy[9,10]. Recent research has also demonstrated the safety and diagnostic efficacy of transpapillary biopsies, NOTES biopsies, and EUS-guided fine needle aspiration/fine needle biopsy of gallbladder lesions[11]. The use of advanced imaging techniques like EUS, magnifying endoscopy, chromoendoscopy, and CLE, coupled with targeted biopsies within the gallbladder inner wall, facilitates the management of high-risk gallbladder polyps, eliminating high-risk factors and attaining primary prevention goals for GBC[12,13].

Second, palliative endoscopic treatment for patients with advanced GBC is one of the earliest areas involved in GBC endoscopic therapy. The previous endoscopic treatments for advanced GBC patients primarily aimed to improve biliary obstruction through endoscopic retrograde cholangiopancreatography or percutaneous transhepatic cholangioscopy and alleviate gastric outlet obstruction via endoscopic dilation or gastrointestinal stenting. With the advent of EUS, SpyGlass™ Direct Visualization system, lumen-apposing metal stents, and other novel endoscopic equipment, the specific procedures and success rates of the above operations have been optimized[14]. Moreover, innovative and effective endoscopic diagnostic and therapeutic methods have emerged, including EUS-guided gastroenterostomy, EUS-guided celiac plexus neurolysis, photodynamic therapy, radiofrequency ablation, and intraluminal brachytherapy[15,16]. These advances contribute to more minimally invasive and effective treatment goals for patients with advanced GBC, such as pain relief, suppressing tumor progression, and improving gastrointestinal and biliary obstructions.

Third, advancing endoscopic equipment and techniques have offered expanded possibilities for minimally invasive endoscopic surgery for gallbladder diseases. Current endoscopic methods have been able to achieve a series of medical objectives in the diagnosis and treatment of acute cholecystitis, gallbladder stones, gallbladder polyps, and gallbladder tumors, such as targeted biopsy for definitive diagnosis, removal of stones or polyps, and alleviation of obstruction or pain symptoms[12,17]. Treating gallbladder inflammation, polyps, and stones through endoscopic procedures helps prevent or reduce the occurrence of GBC. Moreover, a systematic review found that patients with T1a GBC had a 5-year survival rate of up to 100% after cholecystectomy alone[18]. From this perspective, endoscopic cholecystectomy via NOTES could theoretically be an effective and minimally invasive option for early-stage GBC (Tis and T1a) patients. Even more, implementing a whole-process management approach that encompasses early endoscopic detection of GBC (Tis and T1a) in high-risk patients, minimally invasive endoscopic surgical removal of the gallbladder, and endoscopic postoperative surveillance may establish a novel model for the entire management of these early-stage GBC patients using endoscopic techniques.

NEW NEEDS AND NEW MODELS

“Prevention is always better than cure”, this adage also holds for GBC. In the current landscape of diverse and often conflicting health information, accessing accurate and beneficial cancer prevention information has become an urgent need for people worldwide, especially those at high risk of GBC. Public health initiatives aimed at educating people about risk factors associated with GBC, such as obesity, gallstones, chronic inflammation of the gallbladder, and factors contributing to increased mortality rates like the consumption of red meat, can help reduce the incidence and improve the prognosis for GBC patients[19-22]. Moreover, promoting regular check-ups, particularly in high-risk regions and populations, can lead to early detection and better outcomes.

In the context of increasing health consciousness and elevated expectations for medical efficacy, there is a significant and growing demand for a comprehensive and integrated suite of medical services, particularly in regions with a high prevalence of GBC. These services should encompass GBC risk prediction, differential diagnoses for suspicious lesions, precise preoperative staging, minimally invasive intervention options, and comprehensive postoperative surveillance, all geared towards the early detection and diagnosis of this relentless killer to enhance treatment success and prolong survival[19]. The advantages of endoscopy in direct visualization and targeted biopsy of early-staged GBC, eradicating high-risk factors, removal of early-stage lesions, and high-quality postoperative surveillance are indispensable in meeting these needs. For patients with advanced GBC, palliative care is crucial for improving their QoL. Pain management, symptom control, and psychological support are vital components of palliative care. Further integrating and standardizing applicable palliative treatments can substantially improve patients’ sense of well-being during and after therapy[15,23,24].

Meanwhile, the complexity of GBC necessitates a collaborative effort among various medical disciplines. A multidisciplinary team of gastroenterologists, surgeons, endoscopists, oncologists, radiologists, pathologists, and support staff can provide comprehensive medical care that addresses the entire spectrum of GBC management[25,26]. These professionals can ensure that GBC patients receive the most appropriate and effective treatment plans based on the latest research and individualized needs. Another fascinating development in the field is the potential integration of artificial intelligence technologies and machine learning methods into GBC practice. These advanced technologies have seen rapid progress in recent years and promise to improve early diagnosis and prognosis prediction in GBC patients[27,28]. The multidisciplinary team may more accurately identify and characterize lesions, predict disease progression, and develop personalized treatment plans using artificial intelligence and machine learning.

To achieve early diagnosis of GBC for optimal treatment outcomes, our endoscopy center recommends incorporating EUS examination of the gallbladder inner wall as a quality control indicator for high-risk GBC patients. We also advocate using EUS-guided elastography, contrast-enhanced EUS, trans-papillary biopsy, and NOTES biopsy when necessary. Additionally, we recommend regular endoscopic follow-up, including EUS, for post-cholecystectomy GBC patients to improve the quality of postoperative monitoring. Our explorations may provide valuable insights for endoscopic practices in GBC patients, and we expect to share our work with colleagues worldwide once we have gathered sufficient data.

CONCLUSION

In conclusion, the endoscopic diagnosis and management of GBC have seen significant advancements in recent years, with a growing emphasis on early detection and minimally invasive treatment options. With the ongoing advancements in endoscopic equipment and techniques, further research and exploration are likely to lead to more minimally invasive and high-quality approaches to meeting the medical needs of GBC patients.