Purpose, use, and preparation of clinical practice guidelines for the management of biliary tract and ampullary carcinomas

Apart from periampullary carcinoma, the prognosis of biliary tract carcinomas, including hilar cholangiocarcinoma, extrahepatic biliary tract carcinoma, and gallbladder carcinoma, remains poor. Sophisticated diagnostic skills and treatment methods and their application are naturally required to achieve better treatment results for biliary tract carcinomas. However, it is not too much to say that, due to the paucity of high-level evidence for the management of these carcinomas, medical care by healthcare providers in clinics and at medical institutes throughout the world is currently delivered without common consensus and common standards. The clinical practice guidelines for the management of biliary carcinoma outlined here were produced with the aim that they could be used by physicians involved in the care of biliary tract carcinomas, as indicators that could help them provide their patients with the most appropriate care possible at this time. Also, the guidelines were prepared to provide measures that could assure patients with biliary tract carcinomas of safe medical care. The present guidelines are characterized by their clarification of clinical questions assumed to be often shared by healthcare professionals. For clarity, we divided the contents of the guidelines into eight areas. In each area, clinical questions are presented, together with recommendations of clinical actions in response to the question. As mentioned already, there is a paucity of high-level evidence in this area; therefore, the recommendations are classifi ed into grades, of which there are fi ve: A, strongly recommend performing the clinical action; B, recommend performing the clinical action; C1, the clinical action may be useful, although there is a lack of high-level scientifi c evidence; C2, clinical action not defi nitively recommended because of insuffi cient scientifi c evidence; D, recommend not performing the clinical action. The grading of the recommendations is based on the determination of the level of evidence in references on which the recommendation is based.

## Purpose of the clinical practice guidelines for the management of biliary tract and ampullary carcinomas (the guidelines)
No guidelines for the diagnosis and treatment of biliary tract carcinoma, the prognosis of which remains poor, have been published to date, although a set of guidelines for intrahepatic cholangiocarcinoma was published in 2002 by There remain many problems to be solved concerning the diagnosis and treatment of biliary tract carcinoma so that better treatment results can be achieved for this disease. We (The Japanese Society of Hepato-Biliary-Pancreatic Surgery [JSHBPS]) produced the present guidelines, recognizing that a high level of expertise is required for those concerned with the diagnosis and treatment of the disease. The greatest obstacle encountered most frequently in preparing the present guidelines was the paucity of high-level evidence for the diagnosis and treatment of biliary tract carcinoma and the lack of practical guidelines for coping with this problem. Currently, under these circumstances, there are wide disparities in the levels of diagnosis and treatment among different institutions. However, in assessing the strength of recommendations for treatment, because of the paucity of high-level evidence in this fi eld, the members of the Organizing Committee formed for creating the guidelines focused on building a concensus. Occasionally, decisions were subject to modifi cations on the basis of discussions at an open forum. The aim of the guidelines was to supply indicators to physicians involved in the care of this disease, to provide their patients with the safest and most appropriate care.

## Notes on the use of the guidelines
The entire contents of the present guidelines were endorsed upon discussions held among all the members of the Organizing Committee and the Publishing Committee. The guidelines consist of algorithms that outline diagnosis and treatment, followed by clinical questions. In view of the fact that there is still a wide variation in treatment policies among medical institutions, the presentation of the contents is made in the form of clinical questions. [bib_ref] JPN Guidelines for the management of acute pancreatitis: cutting-edge information, Takada [/bib_ref] [bib_ref] Tokyo guidelines for the management of acute cholangitis and cholecystitis, Takada [/bib_ref] The contents are divided into eight areas to elucidate the clinical questions considered to be shared by healthcare professionals and to clarify the guidelines with respect to these questions at this stage of publication. The questions in each area are presented under the heading of "clinical questions." The presence or absence of recommendations for a clinical action, the strength of the recommendations, and statements on how recommendations are made are provided with each question. Recommendations and statements are formulated on the basis of evidence. The strength of treatment recommendations in response to each question was determined in accordance with the following policy. Compared with breast cancer and gastric cancer, only a limited amount of high-level evidence has been obtained from randomized controlled trials for the diagnosis and treatment of biliary tract carcinoma. As a result, we aimed to reach a consensus on the grading of the strength of recommendations. This was done and the strength of recommendations was stated according to fi ve grades:
A, Strongly recommend performing the clinical action. B, Recommend performing the clinical action. C1, Clinical action may be useful although there is a lack of high-level scientifi c evidence. C2, Not defi nitively recommended, because of insufficient scientifi c evidence. D, Recommend not performing the clinical action.

## Perspective on "guidelines"
With regard to the present guidelines, from the perspective of "guidelines," they represent the most standard clinical and practical indicators at this time. However, they should not be coercive for the practical management of individual patients. Final decisions on management should be made on the basis of conditions at individual institutions (depending on personnel, experience, instruments, etc.) and the individual characteristics of patients.
The Japanese Society of Hepato-Biliary-Pancreatic Surgery (JSHBPS) is responsible for the statements in the present guidelines. The JSHBPS and the Organizing Committee members are not liable for any consequences arising from any treatment, for which individual physicians involved in the treatment should be responsible. The dosages described in the text are for adult patients.

## How the guidelines were formulated
With evidence-based medicine (EBM) as the core concept, the fi rst Preparation Committee for "the guidelines for the management of biliary tract carcinoma" was held on May 12, 2005, to discuss how to formulate the guidelines. The guidelines were prepared according to the following procedures: (1) 7) Check of the fi nal draft by all committee members. (8) Assessment by the members of the Review Committee of the draft prepared according to the above procedures. (9) A public hearing was held to hear opinions from an audience with wide medical specialties. (10) New committee members of the Publishing Committee were elected from the Organizing Committee to further review the fi nal draft. So that the draft would be objective and evidence-based, it was further checked for consistency in the strength of recommendations and statements of clinical questions. The statements were modifi ed to be more readable. Thus, the fi nal draft was prepared.

## Comprehensive literature search
References written in English were searched for on MEDLINE in June 2005. Reference formulas used and the number of items retrieved are shown below. Systematic review articles were also searched for using the formulas below. References were further searched for, where necessary, by means of a manual search.

## Tiab]) or overviewed [tiab]) or overviewer [tiab]) or overviewing [tiab]) or overviews [tiab])) or clinical trial [pt]) or multicenter study[pt]) or evaluation studies[pt]) or validation studies [pt]) or review [pt]) or (systematic review [all fields] or systematic reviews [all fields])) -182 7246 items search 2 and search 3, but not search 1, -314 items

## Final selection of appropriate references by publishing committee members
On the basis of an evaluation by at least two Publishing Committee members of the importance of abstracts of selected references, 669 English-language references were fi nally selected.

## Preparation of drafts of clinical questions
Using the literature thus selected as references, drafts of clinical questions were prepared by the responsible Publishing Committee members, and 227 questions in total were proposed.

## Final selection of clinical questions from the drafts
At a general meeting held on July 10, 2006, the decision was made that 33 clinical questions should be adopted for each of the eight specialized areas.

## Preparation of statements for clinical questions
The statements of clinical questions and introductions were prepared for each specialized area by the responsible Publishing Committee members. Another general meeting was held and the number of clinical questions to be adopted was changed to 35.
The strength of recommendations for individual clinical questions was given in related statements. Determination of the level of evidence for individual references, on which the strength of recommendations was determined, was made according to the criteria shown in Tables 1 and 2. In view of the lack of high-level evidence on the treatment of biliary tract carcinoma, the decisions on treatment policies were made by taking into account the fi ndings collected from case studies. [fig_ref] Table 1: Strength of recommendations [/fig_ref] The "grade of recommendations" was discussed many times at an Organizing Committee meeting and at a second public hearing meeting. There are many criteria for the strength of recommendations in many clinical practice guidelines, and there are no worldwide standards. After all the discussions, we were able to reach the following consensus on the grading of the strength

## Strength of recommendations and evaluation of evidence levels

## Decisions on clinical questions and review of algorithms
The statements for the clinical questions were modifi ed by the responsible Publishing Committee members. A further general meeting was held to review all the clinical questions. The fi nal number of questions was changed to 36. Diagnosis and treatment algorithms were also prepared.

## Evaluation by review committee members
Evaluations and suggestions for the fi nal draft were made by the External Review Committee. Additions and modifi cations were made after discussions by the Publishing Committee members.

## Public hearing
At two public hearings (the fi rst on June 7, 2007; the 19 th Annual Meeting of the JSHPBS, and the second, on September 29, 2007; the 43 rd Annual Meeting of Japan Biliary Association), comments were requested from the audience, particularly from physicians from a wide area of medical specialties, and then the fi nal corrections of the draft were made.

## Publishing committee
The Publishing Committee was organized after the fi rst public hearing. Reexaminations, additions, and corrections were made with respect to all the expressions, sentences, and terminology, etc., by all the Publishing Committee members. For the contents, repeated discussions were held until a suffi cient consensus was achieved.
The fi nal version of the fi nal draft was made public at the second public hearing, and comments from the general audience were requested. The fi nal version was also evaluated by the External Review Committee members. The draft was fi nalized taking into account these comments and the evaluation.

## Diffusion of the guidelines
The guidelines, Evidence-based clinical practice guidelines for the management of biliary tract carcinoma, were published in Japanese by Igaku-Tosyo Syuppan.
The guidelines were posted on the Internet on the JSHBPS home page, Japan Council for Quality Health Care; and, on the medical information network distribution service (Minds) home page.

## Plan for publication of the revised edition
Evaluation and accumulation of pertinent evidence is being continued by the Organizing Committee of the guidelines, which has been established permanently at the JSHBPS. A revised edition is expected to be published every 4 years, but the timing of the revisions will be subject to change depending upon advances in medical science and care.
[fig] Funding: Finance for the preparation of the present guidelines was provided under the auspices of a research subsidy for fi scal 2005 and 2006 (Integrated Research Project for Assessing Medical Safety and Medical Technology, sponsored by the Japanese Ministry of Health, Labour, and Welfare, and the JSHBPS). [/fig]
[table] Table 1: Strength of recommendations [/table]