Ambulatory Endoscopic Diagnosis of Pathology of the Major Duodenal Papilla

The research is devoted to ambulatory endoscopic diagnosis of pathology of the major duodenal papilla — a common problem in surgical gastroenterology, as the papilla is involved in the pathological process in the majority of diseases of the biliary tract and pancreas. The work develops a comprehensive diagnostic program including a modified method of endoscopic biopsy and a quantitative method of laser DNA flow cytometry for differential diagnosis of benign and malignant lesions, as well as a method of minimally invasive endoscopic removal of papillary adenomas. The investigation covers three main types of pathological changes: inflammatory, tumor-like, and tumorous, and substantiates their relationship with diseases of the biliary tract, pancreas, and chronic hyperacidic gastritis associated with Helicobacter pylori.

Relevance of the Topic

Lesions of the major duodenal papilla (MDP) are a common pathology in surgical gastroenterology, as the papilla is involved in the pathological process in the majority of diseases of the biliary tract and pancreas [95]. The high prevalence of cholelithiasis (CH), together with the refinement of surgical treatment methods, has led to a significant increase in the number of operations on the gallbladder and biliary tract [75]. The necessity of comprehensive clinical analysis both before and after surgical interventions for CH [74] determines the importance of timely diagnosis of pathological changes of the MDP. Diagnosis of these changes is a challenging task due to the peculiarities of anatomical location, as well as the absence of a characteristic clinical picture and changes in laboratory parameters. The relevance of questions of endoscopic diagnosis of pathological changes of the MDP is determined by significant progress in endoscopic instruments and methods, as well as the accumulation of experience by researchers specializing in the field of flexible gastrointestinal endoscopy.

Endoscopic diagnosis of MDP lesions requires performing duodenoscopy with targeted examination of the papillary area. In this case, based on visual examination of the MDP, a particular pathological process may be suspected. For this purpose, characteristics are needed that would correspond to accepted international standards, in particular, the minimal standard terminology of digestive endoscopy [98], and, at the same time, would allow as complete a description as possible of the endoscopic picture of the process.

The development and implementation into clinical practice over the last two decades of the principles of evidence-based medicine require clarification of the clinicomorphological characteristics of pathological changes of the MDP. It is known, for example, that stenosing processes of the MDP lead to the development of extrahepatic cholestasis and biliary hypertension, as well as the obstructive form of chronic pancreatitis — the second type of chronic pancreatitis according to the Marseille-Rome classification, which is also the second most common (up to 20%). Determination of the morphological characteristics underlying these processes serves to reveal the cause-and-effect relationships of MDP diseases and organs of the biliopancreatic duodenal area, to predict the development of these diseases, and to select the treatment method: conservative or surgical, which should be applied in a specific case. For morphological verification of the diagnosis, endoscopic biopsy is performed. An accepted method for MDP biopsy does not exist today.

Modern capabilities of morphological diagnosis at the cellular level are not limited to the use of traditional histological and cytological methods, where a conclusion is based on the determination of qualitative characteristics of the pathological process. The principles of evidence-based medicine dictate the necessity of involving modern methods of quantitative morphological assessment. Thus, significant difficulties in differential diagnosis of benign and malignant MDP processes arise when detecting dysplastic changes of adenomatous structures. Great interest is aroused by the method of laser DNA flow cytometry, which allows assessment of cell cycle phases, degree of proliferative activity, ploidy of cells, and thereby determine the nature of pathological changes: benign or malignant [41].

Tumors of the MDP and the terminal part of the common bile duct constitute 2–7% of all neoplasms and 10% of gastrointestinal tract tumors. A special place among tumorous lesions of the MDP is occupied by adenomas. Their clinical significance is determined by their anatomical location at the junction of three most important structures of the digestive organ system: the duodenum, the common bile duct, and the main pancreatic duct, as well as the risk of malignant transformation. [5, 22, 26, 35, 52, 64, 84, 111, 139, 151, 170, 182]. The constant search for less invasive methods of treating tumor processes, together with the progress of endoscopic technique over the last two decades, necessitates the development of a method of minimally invasive endoscopic removal of MDP adenomas.

Objective of the Research

To improve the results of ambulatory endoscopic diagnosis of MDP pathology.

Tasks of the Research

1. To determine the main types of pathological changes of the MDP encountered during planned ambulatory endoscopic investigations.

2. To determine the possibilities of visual endoscopic assessment of the main types of MDP pathology.

3. To investigate the capabilities of endoscopic biopsy of the MDP.

4. To clarify the indications for laser DNA flow cytometry in differential diagnosis of MDP pathology.

Scientific Novelty

Data have been obtained confirming the effectiveness of the developed method of endoscopic biopsy of the MDP, the novelty of which is confirmed by Russian Federation Patent No. 2230494 dated 20.06.2004. It has been proven that the method allows determination of morphological characteristics of pathological changes of the MDP both from the duodenal surface and from the ampulla of the MDP, and thus improves the results of diagnosis of such changes.

Data have been obtained for the first time on the capabilities of the quantitative morphological method of laser DNA flow cytometry for diagnosing MDP lesions. On the example of 27 cases where dysplasia of epithelial structures of moderate and severe degree was present, the effectiveness of the method for differential diagnosis of benign and malignant MDP changes has been demonstrated.

The effectiveness of the developed method of endoscopic removal of MDP adenomas has been demonstrated, the novelty of which is confirmed by Russian Federation Patent No. 2226363 dated 10.04.2004. An assessment of immediate and remote results of application of this method in 15 patients has been conducted.

It has been established for the first time that in the overwhelming majority of cases of pathological changes of the MDP — 244 (83.9%) — there was colonization of the gastric mucosa by Helicobacter pylori (H. pylori). In this case, medium and high degrees of colonization of H. pylori mucosa were more often determined: a total of 190 (75.2%) cases in the overall patient group. The highest degree of colonization of gastric mucosa by H. pylori was registered in the group of tumor-like MDP lesions: 31 (48%) cases, which is higher than in papillitis — 59 (31.9%) cases and MDP tumors — 4 (22.2%) cases.

Practical Significance of the Work

Using a comprehensive diagnostic program, MDP pathology was clarified in 267 patients. This constituted 2.9% of the total flow of planned endoscopic investigations in the polyclinic. In the majority of cases (55.1%), these were patients of working age (41–60 years), among whom women were 3.7 times more than men. It was established that pathological changes of the MDP are represented by three fundamentally different pathological processes: inflammatory — 185 (69.3%) cases, tumor-like — 64 (24%) cases, and tumorous — 18 (6.7%) cases. Based on obtained laboratory and instrumental data, the relationship of MDP lesions with diseases of the biliary tract and pancreas was confirmed in all cases, as well as with chronic hyperacidic H. pylori-associated gastritis — in 83.9% of cases. It was determined that in patients with tumor-like and tumorous MDP lesions, more frequent elevation of bilirubin, gamma-glutamyl transferase (GGT), and alkaline phosphatase (ALP) levels is registered, and in patients with MDP tumors also aminotransferases, which indicates more serious obstacles to bile outflow in these patients compared to patients with papillitis. These differences are confirmed by ultrasound data. Thus, during ultrasound, more frequent dilation of the common bile duct and main pancreatic duct was registered, indicating the presence of biliary and pancreatic hypertension, in patients with tumor-like and tumorous MDP lesions. The work demonstrates that performing duodenoscopy with visual assessment and biopsy of the MDP using a modified technique allows determination of the type of pathological changes of the MDP and to outline paths of optimal treatment. On the example of 27 cases, the possibilities of practical application of the quantitative method of laser DNA flow cytometry for differential diagnosis of benign and malignant MDP processes in cases of detection of dysplasia of epithelial structures of moderate and severe degree have been shown. The work demonstrates that the modified method of endoscopic removal of MDP adenomas applied in 15 patients is effective and can be used in clinical practice.

Implementation into Clinical Practice

The developed diagnostic program, improved methods of endoscopic biopsy of MDP lesions, and endoscopic removal of MDP adenomas have been implemented into clinical practice of endoscopic departments of the polyclinic and hospital of Medical-Sanitary Unit No. 31 of the Ural Electrochemical Combine and the Medical Center of the Central Bank of the Russian Federation in Moscow.

Main Propositions for Defense

1. Pathological changes of the MDP occupy a substantial place in the structure of pathological changes detected during planned ambulatory endoscopic investigations of the upper gastrointestinal tract (2.9% of the total number of endoscopic investigations) and are divided into three main types: inflammatory, tumor-like, and tumorous lesions of the MDP.

2. Endoscopic examination of the papillary area and MDP during duodenoscopy serves as a screening method and allows suspicion of one of three types of MDP pathological changes.

3. The modified method of MDP biopsy allows verification of the type of MDP lesion in cases where traditional morphological evaluation is performed.

4. The quantitative morphological method of DNA flow cytometry is indicated for differential diagnosis of benign and malignant MDP processes in cases of detection of dysplasia of epithelial structures of moderate and severe degree.

Presentation of the Work

The dissertation topic was included in the research plan of the Department of Surgery of the Faculty of Advanced Training and Professional Retraining of the Ural State Medical Academy (head of the department, Doctor of Medical Sciences, Professor Prudkov M.I.).

The main provisions of the dissertation work were reported at the 4th and 8th Russian Gastroenterological Weeks (Moscow, 1998, 2002), at the First All-Russian Congress of the Russian Society of Digestive Endoscopy (Moscow, 2002), at the Interregional Scientific-Practical Conference on Surgery of Destructive Cholecystitis (Yekaterinburg, 2002), at the 7th International Congress on Endoscopy and Endoscopic Surgery (Moscow, 2003), at the Annual Meeting of the Regional Surgical Society (Yekaterinburg, 2004), at the 5th European Gastroenterological Week (Paris, France, 1996), and the World Congress of Gastroenterologists (Vienna, Austria, 1998).

Based on the materials of the work, two inventions have been patented:

1. «Method of Biopsy of the Mucous Membrane of the Major Duodenal Papilla During Duodenoscopy», invention patent No. 2230494, registered in the State Register of Inventions of the Russian Federation on 20.06.2004.

2. «Method of Endoscopic Removal of Adenomas of the Major Duodenal Papilla», invention patent No. 2226363, registered in the State Register of Inventions of the Russian Federation on 10.04.2004.

The dissertation materials were reported and discussed at the scientific-practical conference of the Department of Surgery of the Faculty of Advanced Training and Professional Retraining of the Ural State Medical Academy.

The dissertation work was presented at the meeting of the problem commission on surgery of the Ural State Medical Academy.

Publications on the Topic of the Work

8 printed works have been published on the topic of the dissertation.

Form of Implementation

Publications of the research results in the central press, reports at scientific conferences.

Structure and Volume of the Dissertation

The dissertation consists of an introduction, a literature review, four chapters, a conclusion, conclusions, practical recommendations, and a list of references. The latter includes 183 sources, including 98 domestic and 85 foreign. The dissertation is presented on 118 pages of typed text and contains 21 tables and 26 figures.