Journal of Clinical and Diagnostic Research, ISSN - 0973 - 709X

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Dr Bhanu K Bhakhri

"The Journal of Clinical and Diagnostic Research (JCDR) has been in operation since almost a decade. It has contributed a huge number of peer reviewed articles, across a spectrum of medical disciplines, to the medical literature.
Its wide based indexing and open access publications attracts many authors as well as readers
For authors, the manuscripts can be uploaded online through an easily navigable portal, on other hand, reviewers appreciate the systematic handling of all manuscripts. The way JCDR has emerged as an effective medium for publishing wide array of observations in Indian context, I wish the editorial team success in their endeavour"



Dr Bhanu K Bhakhri
Faculty, Pediatric Medicine
Super Speciality Paediatric Hospital and Post Graduate Teaching Institute, Noida
On Sep 2018




Dr Mohan Z Mani

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Department of Dematolgy,
Believers Church Medical College,
Thiruvalla, Kerala
On Sep 2018




Prof. Somashekhar Nimbalkar

"Over the last few years, we have published our research regularly in Journal of Clinical and Diagnostic Research. Having published in more than 20 high impact journals over the last five years including several high impact ones and reviewing articles for even more journals across my fields of interest, we value our published work in JCDR for their high standards in publishing scientific articles. The ease of submission, the rapid reviews in under a month, the high quality of their reviewers and keen attention to the final process of proofs and publication, ensure that there are no mistakes in the final article. We have been asked clarifications on several occasions and have been happy to provide them and it exemplifies the commitment to quality of the team at JCDR."



Prof. Somashekhar Nimbalkar
Head, Department of Pediatrics, Pramukhswami Medical College, Karamsad
Chairman, Research Group, Charutar Arogya Mandal, Karamsad
National Joint Coordinator - Advanced IAP NNF NRP Program
Ex-Member, Governing Body, National Neonatology Forum, New Delhi
Ex-President - National Neonatology Forum Gujarat State Chapter
Department of Pediatrics, Pramukhswami Medical College, Karamsad, Anand, Gujarat.
On Sep 2018




Dr. Kalyani R

"Journal of Clinical and Diagnostic Research is at present a well-known Indian originated scientific journal which started with a humble beginning. I have been associated with this journal since many years. I appreciate the Editor, Dr. Hemant Jain, for his constant effort in bringing up this journal to the present status right from the scratch. The journal is multidisciplinary. It encourages in publishing the scientific articles from postgraduates and also the beginners who start their career. At the same time the journal also caters for the high quality articles from specialty and super-specialty researchers. Hence it provides a platform for the scientist and researchers to publish. The other aspect of it is, the readers get the information regarding the most recent developments in science which can be used for teaching, research, treating patients and to some extent take preventive measures against certain diseases. The journal is contributing immensely to the society at national and international level."



Dr Kalyani R
Professor and Head
Department of Pathology
Sri Devaraj Urs Medical College
Sri Devaraj Urs Academy of Higher Education and Research , Kolar, Karnataka
On Sep 2018




Dr. Saumya Navit

"As a peer-reviewed journal, the Journal of Clinical and Diagnostic Research provides an opportunity to researchers, scientists and budding professionals to explore the developments in the field of medicine and dentistry and their varied specialities, thus extending our view on biological diversities of living species in relation to medicine.
‘Knowledge is treasure of a wise man.’ The free access of this journal provides an immense scope of learning for the both the old and the young in field of medicine and dentistry as well. The multidisciplinary nature of the journal makes it a better platform to absorb all that is being researched and developed. The publication process is systematic and professional. Online submission, publication and peer reviewing makes it a user-friendly journal.
As an experienced dentist and an academician, I proudly recommend this journal to the dental fraternity as a good quality open access platform for rapid communication of their cutting-edge research progress and discovery.
I wish JCDR a great success and I hope that journal will soar higher with the passing time."



Dr Saumya Navit
Professor and Head
Department of Pediatric Dentistry
Saraswati Dental College
Lucknow
On Sep 2018




Dr. Arunava Biswas

"My sincere attachment with JCDR as an author as well as reviewer is a learning experience . Their systematic approach in publication of article in various categories is really praiseworthy.
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It's a honour and pride to be a part of the JCDR team. My very best wishes to JCDR and hope it will sparkle up above the sky as a high indexed journal in near future."



Dr. Arunava Biswas
MD, DM (Clinical Pharmacology)
Assistant Professor
Department of Pharmacology
Calcutta National Medical College & Hospital , Kolkata




Dr. C.S. Ramesh Babu
" Journal of Clinical and Diagnostic Research (JCDR) is a multi-specialty medical and dental journal publishing high quality research articles in almost all branches of medicine. The quality of printing of figures and tables is excellent and comparable to any International journal. An added advantage is nominal publication charges and monthly issue of the journal and more chances of an article being accepted for publication. Moreover being a multi-specialty journal an article concerning a particular specialty has a wider reach of readers of other related specialties also. As an author and reviewer for several years I find this Journal most suitable and highly recommend this Journal."
Best regards,
C.S. Ramesh Babu,
Associate Professor of Anatomy,
Muzaffarnagar Medical College,
Muzaffarnagar.
On Aug 2018




Dr. Arundhathi. S
"Journal of Clinical and Diagnostic Research (JCDR) is a reputed peer reviewed journal and is constantly involved in publishing high quality research articles related to medicine. Its been a great pleasure to be associated with this esteemed journal as a reviewer and as an author for a couple of years. The editorial board consists of many dedicated and reputed experts as its members and they are doing an appreciable work in guiding budding researchers. JCDR is doing a commendable job in scientific research by promoting excellent quality research & review articles and case reports & series. The reviewers provide appropriate suggestions that improve the quality of articles. I strongly recommend my fraternity to encourage JCDR by contributing their valuable research work in this widely accepted, user friendly journal. I hope my collaboration with JCDR will continue for a long time".



Dr. Arundhathi. S
MBBS, MD (Pathology),
Sanjay Gandhi institute of trauma and orthopedics,
Bengaluru.
On Aug 2018




Dr. Mamta Gupta,
"It gives me great pleasure to be associated with JCDR, since last 2-3 years. Since then I have authored, co-authored and reviewed about 25 articles in JCDR. I thank JCDR for giving me an opportunity to improve my own skills as an author and a reviewer.
It 's a multispecialty journal, publishing high quality articles. It gives a platform to the authors to publish their research work which can be available for everyone across the globe to read. The best thing about JCDR is that the full articles of all medical specialties are available as pdf/html for reading free of cost or without institutional subscription, which is not there for other journals. For those who have problem in writing manuscript or do statistical work, JCDR comes for their rescue.
The journal has a monthly publication and the articles are published quite fast. In time compared to other journals. The on-line first publication is also a great advantage and facility to review one's own articles before going to print. The response to any query and permission if required, is quite fast; this is quite commendable. I have a very good experience about seeking quick permission for quoting a photograph (Fig.) from a JCDR article for my chapter authored in an E book. I never thought it would be so easy. No hassles.
Reviewing articles is no less a pain staking process and requires in depth perception, knowledge about the topic for review. It requires time and concentration, yet I enjoy doing it. The JCDR website especially for the reviewers is quite user friendly. My suggestions for improving the journal is, more strict review process, so that only high quality articles are published. I find a a good number of articles in Obst. Gynae, hence, a new journal for this specialty titled JCDR-OG can be started. May be a bimonthly or quarterly publication to begin with. Only selected articles should find a place in it.
An yearly reward for the best article authored can also incentivize the authors. Though the process of finding the best article will be not be very easy. I do not know how reviewing process can be improved. If an article is being reviewed by two reviewers, then opinion of one can be communicated to the other or the final opinion of the editor can be communicated to the reviewer if requested for. This will help one’s reviewing skills.
My best wishes to Dr. Hemant Jain and all the editorial staff of JCDR for their untiring efforts to bring out this journal. I strongly recommend medical fraternity to publish their valuable research work in this esteemed journal, JCDR".



Dr. Mamta Gupta
Consultant
(Ex HOD Obs &Gynae, Hindu Rao Hospital and associated NDMC Medical College, Delhi)
Aug 2018




Dr. Rajendra Kumar Ghritlaharey

"I wish to thank Dr. Hemant Jain, Editor-in-Chief Journal of Clinical and Diagnostic Research (JCDR), for asking me to write up few words.
Writing is the representation of language in a textual medium i e; into the words and sentences on paper. Quality medical manuscript writing in particular, demands not only a high-quality research, but also requires accurate and concise communication of findings and conclusions, with adherence to particular journal guidelines. In medical field whether working in teaching, private, or in corporate institution, everyone wants to excel in his / her own field and get recognised by making manuscripts publication.


Authors are the souls of any journal, and deserve much respect. To publish a journal manuscripts are needed from authors. Authors have a great responsibility for producing facts of their work in terms of number and results truthfully and an individual honesty is expected from authors in this regards. Both ways its true "No authors-No manuscripts-No journals" and "No journals–No manuscripts–No authors". Reviewing a manuscript is also a very responsible and important task of any peer-reviewed journal and to be taken seriously. It needs knowledge on the subject, sincerity, honesty and determination. Although the process of reviewing a manuscript is a time consuming task butit is expected to give one's best remarks within the time frame of the journal.
Salient features of the JCDR: It is a biomedical, multidisciplinary (including all medical and dental specialities), e-journal, with wide scope and extensive author support. At the same time, a free text of manuscript is available in HTML and PDF format. There is fast growing authorship and readership with JCDR as this can be judged by the number of articles published in it i e; in Feb 2007 of its first issue, it contained 5 articles only, and now in its recent volume published in April 2011, it contained 67 manuscripts. This e-journal is fulfilling the commitments and objectives sincerely, (as stated by Editor-in-chief in his preface to first edition) i e; to encourage physicians through the internet, especially from the developing countries who witness a spectrum of disease and acquire a wealth of knowledge to publish their experiences to benefit the medical community in patients care. I also feel that many of us have work of substance, newer ideas, adequate clinical materials but poor in medical writing and hesitation to submit the work and need help. JCDR provides authors help in this regards.
Timely publication of journal: Publication of manuscripts and bringing out the issue in time is one of the positive aspects of JCDR and is possible with strong support team in terms of peer reviewers, proof reading, language check, computer operators, etc. This is one of the great reasons for authors to submit their work with JCDR. Another best part of JCDR is "Online first Publications" facilities available for the authors. This facility not only provides the prompt publications of the manuscripts but at the same time also early availability of the manuscripts for the readers.
Indexation and online availability: Indexation transforms the journal in some sense from its local ownership to the worldwide professional community and to the public.JCDR is indexed with Embase & EMbiology, Google Scholar, Index Copernicus, Chemical Abstracts Service, Journal seek Database, Indian Science Abstracts, to name few of them. Manuscriptspublished in JCDR are available on major search engines ie; google, yahoo, msn.
In the era of fast growing newer technologies, and in computer and internet friendly environment the manuscripts preparation, submission, review, revision, etc and all can be done and checked with a click from all corer of the world, at any time. Of course there is always a scope for improvement in every field and none is perfect. To progress, one needs to identify the areas of one's weakness and to strengthen them.
It is well said that "happy beginning is half done" and it fits perfectly with JCDR. It has grown considerably and I feel it has already grown up from its infancy to adolescence, achieving the status of standard online e-journal form Indian continent since its inception in Feb 2007. This had been made possible due to the efforts and the hard work put in it. The way the JCDR is improving with every new volume, with good quality original manuscripts, makes it a quality journal for readers. I must thank and congratulate Dr Hemant Jain, Editor-in-Chief JCDR and his team for their sincere efforts, dedication, and determination for making JCDR a fast growing journal.
Every one of us: authors, reviewers, editors, and publisher are responsible for enhancing the stature of the journal. I wish for a great success for JCDR."



Thanking you
With sincere regards
Dr. Rajendra Kumar Ghritlaharey, M.S., M. Ch., FAIS
Associate Professor,
Department of Paediatric Surgery, Gandhi Medical College & Associated
Kamla Nehru & Hamidia Hospitals Bhopal, Madhya Pradesh 462 001 (India)
E-mail: drrajendrak1@rediffmail.com
On May 11,2011




Dr. Shankar P.R.

"On looking back through my Gmail archives after being requested by the journal to write a short editorial about my experiences of publishing with the Journal of Clinical and Diagnostic Research (JCDR), I came across an e-mail from Dr. Hemant Jain, Editor, in March 2007, which introduced the new electronic journal. The main features of the journal which were outlined in the e-mail were extensive author support, cash rewards, the peer review process, and other salient features of the journal.
Over a span of over four years, we (I and my colleagues) have published around 25 articles in the journal. In this editorial, I plan to briefly discuss my experiences of publishing with JCDR and the strengths of the journal and to finally address the areas for improvement.
My experiences of publishing with JCDR: Overall, my experiences of publishing withJCDR have been positive. The best point about the journal is that it responds to queries from the author. This may seem to be simple and not too much to ask for, but unfortunately, many journals in the subcontinent and from many developing countries do not respond or they respond with a long delay to the queries from the authors 1. The reasons could be many, including lack of optimal secretarial and other support. Another problem with many journals is the slowness of the review process. Editorial processing and peer review can take anywhere between a year to two years with some journals. Also, some journals do not keep the contributors informed about the progress of the review process. Due to the long review process, the articles can lose their relevance and topicality. A major benefit with JCDR is the timeliness and promptness of its response. In Dr Jain's e-mail which was sent to me in 2007, before the introduction of the Pre-publishing system, he had stated that he had received my submission and that he would get back to me within seven days and he did!
Most of the manuscripts are published within 3 to 4 months of their submission if they are found to be suitable after the review process. JCDR is published bimonthly and the accepted articles were usually published in the next issue. Recently, due to the increased volume of the submissions, the review process has become slower and it ?? Section can take from 4 to 6 months for the articles to be reviewed. The journal has an extensive author support system and it has recently introduced a paid expedited review process. The journal also mentions the average time for processing the manuscript under different submission systems - regular submission and expedited review.
Strengths of the journal: The journal has an online first facility in which the accepted manuscripts may be published on the website before being included in a regular issue of the journal. This cuts down the time between their acceptance and the publication. The journal is indexed in many databases, though not in PubMed. The editorial board should now take steps to index the journal in PubMed. The journal has a system of notifying readers through e-mail when a new issue is released. Also, the articles are available in both the HTML and the PDF formats. I especially like the new and colorful page format of the journal. Also, the access statistics of the articles are available. The prepublication and the manuscript tracking system are also helpful for the authors.
Areas for improvement: In certain cases, I felt that the peer review process of the manuscripts was not up to international standards and that it should be strengthened. Also, the number of manuscripts in an issue is high and it may be difficult for readers to go through all of them. The journal can consider tightening of the peer review process and increasing the quality standards for the acceptance of the manuscripts. I faced occasional problems with the online manuscript submission (Pre-publishing) system, which have to be addressed.
Overall, the publishing process with JCDR has been smooth, quick and relatively hassle free and I can recommend other authors to consider the journal as an outlet for their work."



Dr. P. Ravi Shankar
KIST Medical College, P.O. Box 14142, Kathmandu, Nepal.
E-mail: ravi.dr.shankar@gmail.com
On April 2011

Important Notice

Original article / research
Year : 2012 | Month : May | Volume : 6 | Issue : 4 | Page : 692 - 695

Carcinoma of the Gall Bladder: A Prospective Study in a Tertiary Hospital of Bombay, India

Lancelot Lobo, Kishan Prasad H.L., R.R. Satoskar

1. Department of General surgery 2. Department of Pathology, K S Hegde Medical Academy of Nitte University, Mangalore, Karnataka, India. 3. Department of General surgery, Seth GS Medical College, Bombay, India.

Correspondence Address :
Kishan Prasad H.L.
Asst. Professor, Department of Pathology,
K.S. Hegde Medical Academy of Nitte University,
Deralakatte, Mangalore, Karnataka, India.
Phone: 09480503190; E-mail: dr_kishanpath@yahoo.com

Abstract

Introduction: Despite the pre-operative procedures, gall bladder carcinoma is commonly detected intraoperatively or on histopathological examination after cholecystectomy. The prevalence of gall bladder carcinoma is highly variable across the world and it remains the most common malignancy of the biliary tract worldwide. Very high incidence rates are found in northern India and Chile. Gall bladder cancer has been frequently referred as a lethal and incurable disease. Despite the advances in medical imaging, most of the cases (70-80%) of gall bladder cancer are only discovered incidentally on histopathological examination after cholecystectomy which is performed for presumed benign biliary disease. Therefore, the morphological studies have had a significant impact on the diagnosis of this cancer, thus lowering the number of cases that could be under diagnosed and guiding the extent of the surgical resection. Although the subject of gall bladder cancer has been well explored, there is relative paucity of clinicopathological studies on this topic.

Objective: To analyze the demographics, the clinical presentation and the diagnostic modalities in patients with gall bladder carcinoma and to assess the various treatment modalities which have been offered and their results.

Methods: This prospective study was carried out on patients with carcinoma of the gall bladder, who were admitted in a tertiary hospital, Bombay, between 2004 to 2007. After taking the informed consent of the patients, their detailed clinical history which was related to their demographics and their clinical manifestations was taken. Various diagnostic modalities and their TNM staging and treatment were analyzed. All the patients who presented with features which were suggestive of biliary diseases were evaluated by using abdominal ultrasonography and CT, but only those with a confirmatory diagnosis of carcinoma by CT or histopathology were included in the study.

Results: A total of 50 patients were included in the study, with a male:female ratio of 1:2.3. Their ages ranged from 25 to 80 years, with a mean of 54years. Many (34) patients were from the northern states. A lump in the right hypochondrium was seen in 28 patients (56%). It was also noted that 14 patients had presented with obstructive jaundice. Ultrasound and CT revealed a locally advanced disease status in a majority of the cases. Many (90%) cases had associated gall stones. A majority (92%) were in stage IV as was found by TNM staging. Two were identified as incidental findings following cholecystectomy. A majority of the cases were managed with palliative gastrojejunostomy, ERCP stenting and chemoradiotherapy. The cases of early cancer had a better 2 year survival, whereas many of the advanced cases had poor survival rates.

Conclusion: Early detection contributes to a higher survival rate. The prognosis of gall bladder cancer is thus poor, mainly because of the delayed presentation. Besides other factors, TNM staging remains the most imperative prognostic factor which affects the survival. It is desirable to search for any factor which can be linked to gall bladder cancer or which can help in the diagnosis of the disease in the early stages, thus making surgical intervention possible so that it can ultimately result in a good prognosis. Moreover, to positively affect the outcome of the patients in the advanced stage of the disease, newer cancer treatment strategies need to be adopted.

Keywords

Gall bladder, Carcinoma, Prognosis, TNM staging, Follow up

Introduction
Carcinoma of the gall bladder is rare and it is a common malignant tumour of the gall bladder mucosa (1),(2),(3). It is the 5th most common tumour of the gastro-intestinal tract and it accounts for 3% of all the gastro-intestinal tumours. The Indian Council of Medical Research Cancer Registry has recorded an incidence of 4.5 and 10.1 per 100,000 males and females respectively in the northern parts of India, and that of 1.2 per 100,000 population in females in the southern parts of India. Although different associations have been described, gallstones are found to be associated in 70% to 90% of the cases of gall bladder cancer. Approximately 0.4% of all the patients who are affected with gallstones eventually develop carcinoma of the gall bladder. An autopsy study had shown that the overall incidence of carcinoma of the gall bladder is 1% to 3% in patients with cholelithiasis. The most common malignancy is Original Article adenocarcinoma, with a peak incidence in the 6th to 7th decades of life. The five year survival in most of the large series is less than 5%, with a median survival of less than six months (4),(5),(6),(7),(8),(9). The clinical pessimism which surrounds gall bladder carcinoma is due to its late presentation and its lack of effective therapy. Its clinical presentation is non-specific, with a vague symptomatology. The disease is advanced at presentation because the tumour directly involves the liver early and it also invades the adjacent organs. The disease clinically mimics the benign gall bladder diseases and it usually escapes detection until late in its course (3).

5-year survival of 5-10% due to the late detection of the disease [4, 9-12]. Prior to the era of ultrasonography and CT scanning, the rate of the correct pre-operative diagnosis was only 8.6% (4), which has improved considerably to 75–88%, with the use of these newer imaging techniques [11-15]. Still, a pre-operative diagnosis of early carcinoma of the gall bladder is seldom made, where the 5-year survival is 91-100% [16,17]. Most of the available literature has been reported from developed countries which have a sociocultural and health setup, which is different from that of a developing country such as India. This study was aimed at defining the disease profile in the Indian population and at determining the effect of various prognostic parameters on the clinicopathological behaviour of the disease.

Objectives
To analyze the demographics, clinical presentation and the diagnostic modalities in patients with gall bladder carcinoma and to assess the various treatment modalities which have been offered and their results.

Material and Methods

This prospective study was carried out on patients with carcinoma of the gall bladder, who were admitted in a tertiary hospital, Bombay, India between 2004 to 2007. After taking the informed consent of the patients, a detailed clinical history which was related to their demographics and clinical manifestation was taken. Various diagnostic modalities and their TNM staging and treatment were analyzed. All the patients who presented with features which were suggestive of biliary diseases were evaluated by using abdominal ultrasonography and only those with a confirmatory diagnosis which was either by CT or by histopathology means were included in the present study. During this 3-year period, 50 patients with carcinoma of the gall bladder were treated. Haematological, biochemical, and radiological investigations followed a detailed clinical examination to define the extent of the disease and for the general assessment of the patient. The follow- up was carried out at monthly intervals for the first 6 months and thereafter at 3-month intervals.

Results

A total of 50 patients were included in the study who consisted of 35 females and 15 males with a ratio of 2.3;1. Their ages ranged from 25 years to 80 years with a mean of 54years. Among these, 34 patients were from the northern Indian states. Among these, 28 patients (56%) presented with a lump in the right hypochondrim. It was also noted that 14 patients presented with obstructive jaundice. The clinical findings are shown in (Table/Fig 1).

Laboratory Investigations
All the patients underwent routine haematological and biochemical investigations. Among these, 10 cases had anaemia and 6 patients had leucocytosis. The liver function tests were abnormal in 14 patients with obstructive jaundice, with a significant rise in the direct bilirubin and alkaline phosphatase levels. Ultrasonography(USG) was done in all the patients. The findings are shown in (Table/Fig 2). A majority had gall bladder fossa mass with liver extension. Gall stone was detected in 45 cases. A majority of them multiple gall stones. A contrast enhanced computed tomography (CECT) was done in all the cases. The results are shown in (Table/Fig 3). A majority hadfindings which were similar to that of the ultrasound findings. The disease was staged by using TNM staging, based on the CECT findings. The TNM staging is shown in (Table/Fig 4). A majority of the cases (92%) were found to be of stage IV by TNM staging. The treatment which was offered is shown in (Table/Fig 5). 2 patients had a retrospective diagnosis of carcinoma of the gall bladder following cholecystectomy, which was done for suspected chronic cholecystitis. Histopathology revealed adenocarcinoma which was restricted to the submucosa, with no transmural invasion and with transmural invasion in one case each. Both these patients were observed.

Two patients underwent extended cholecystectomy for localized gall bladder carcinoma. Both the patients underwent intraoperative frozen section examination to confirm malignancy before proceeding with the resection. All the 14 patients with obstructed jaundice had advanced disease on imaging. In addition, two patients had gastric outlet obstruction due to invasion of the duodenum. One of these patients underwent palliative gastrojejunostomy (GJ) and segment III bypass. The other patients underwent palliative ERCP stenting and operative GJ. Of the remaining 12 patients, 4 refused any form of therapy and they were discharged. The remaining 8 patients underwent ERCP. ERCP stenting was possible in 5 patients. The remaining 3 patients underwent PTBD (Percutaneous transhepatic biliary drainage) and stenting.

Out of 46 patients with advanced disease, 10 underwent palliative radio chemotherapy and 4 had gastric outlet obstruction, who underwent palliative GJ. Four patients (young patients of < 40years of age) underwent FNAC to prove the diagnosis. 32 patients were symptomatically palliated (narcotic analgesics/ nutritional support).

Follow-up
The follow up was obtained through OPD visits and letters which were sent to the patients. Both the patients with incidental carcinoma were asymptomatic at 2 years of follow up. Of the two patients who underwent extended cholecystectomy, 1 patient developed local recurrence 6 months after the surgery and succumbed to the disease 3 months later. The other patient is asymptomatic at 2 years of follow up. Of the 46 patients with advanced disease, 14 were lost from follow up and 32 succumbed to death within 6 months of the diagnosis. Of the 5 patients who underwent ERCP stenting, 2 developed stent blockage and they underwent repeat ERCP and stent change. Of the 3 patients in whom the PTBD stenting was done, only one was internalized and he was asymptomatic at the end of 6months of follow up. The remaining 2 were discharged with external stents. Two of the 8 patients who were stented are alive at the end of 1year of follow up.

Discussion

Carcinoma of the gall bladder is a rare malignancy which arises from the gall bladder mucosa. It is the 5th most common tumour of the gastro-intestinal tract and it accounts for 3% of all the G.I tract malignancies (1),(3),(6). Its clinical presentation is non-specific, with a vague symptomatology. The disease is advanced at presentation because the tumour directly involves the liver early and it also invades the contiguous organs (1),(10),(11),(12),(13),(14),(15),(16). Because of the advanced stage at presentation, there is no role for curative resection (1),(2),(6). In our study, 50 patients were followed up for over a period of 2 years. The age group of the patients was 25-80years with a maximum incidence in the sixth decade of life, which compared well to the worldwide peak incidence which was reported in the sixth or seventh decades of life (7),(8),(10).

The reported female to male ratio worldwide is 4:1 and we found a ratio of 2.3:1. The disease was found to be more common in the northern states of India. The various risk factors included age, sex, gall stones, diet and chronic inflammation (1),(4). The geographical variations may reflect cultural, dietary or genetic differences in the population. The incidence of gall bladder carcinoma was found tobe more in females than in males because the incidence of gall stones and bladder diseases was more common in females. There was an increased incidence of gall bladder carcinoma in north India because of the increased incidence in gall stones there (1),(4),(9),(16). Physical trauma which was produced by the stones might have resulted in epithelial dysplasia and ultimately in the progression to carcinoma. In our study, 90% of the patients had associated gall stones. Similar results were noted by Khan et al, in 96.15% of the cases (9).

While a histopathological diagnosis is crucial for the discovery of incidental carcinoma (which was diagnosed in two patients in our study and was operated), it is only supportive otherwise, as CT scan is highly sensitive and specific but it also correlates well with the final staging of the disease (9),(10),(11),(12),(13),(14),(15). In other studies, the incidence of occult carcinoma of the gall bladder varied from 1% to 2.5% (9). The staging and the pattern of the spread are clearly defined by the presence or absence of the direct invasion of the adjacent organs, this being the important prognostic factor [1,4,17,18]. Abdominal ultrasound is a valuable screening method for the early detection of the carcinoma, as it is seen as a polypoidal mass or a thickened wall. However, it will detect carcinoma only in 30-50% of the cases. Abdominal CT is a sensitive method and it shows the thickened wall and the contrast enhancement of the gall bladder. Recently, endoscopic ultrasound was found to be valuable in the early detection and staging of the gall bladder carcinoma (6),(10),(12). Despite the advances in hepatobiliary imaging, a precise pre-operative staging for gall bladder carcinoma is still difficult to establish. The overall accuracy of the image-T is 52.6%; however, image-T was a significant predictor of the lymph node metastasis and the patient outcome.

In our study, 50 patients underwent CT scan, which proved to be diagnostic; the recent advances in radiology have increased the diagnostic yield (1),(4),(10),(11),(12),(13),(14),(15). Despite the advances in medical imaging it is still difficult to diagnose gall bladder cancer preoperatively. A gall bladder carcinoma is suspected pre-operatively in only 20%-30% of all the patients; the other 70%-80% of all the cases are detected intra operatively, or are incidentally discovered by the pathologist (1). Pre-operative FNAC was sought in patients of the younger stage groups where a radiological suspicion of malignancy existed. The tissue confirmation of adenocarcinoma was available in our study in 12% of the patients. The early stage disease is rarely picked up since the clinical presentation is uncertain (1),(4),(10),(16),(17),18]. In our study, only 3 patients were in stages I and II. The rest (94%) had advanced disease (stages III and IV) at the time of diagnosis.

The key finding was the lymphatic spread of the gall bladder cancer: the cystic, pericholedochal, and the posterosuperior peripancreatic nodes. By integrating the image-T factor and the data from the intraoperative examination of the frozen sections of the key lymph nodes, the most accurate staging before the resection may be possible. Based on this staging, the algorithms for the surgical treatment of the gall bladder carcinoma can be planned. These algorithms are useful in patients with up to stage IVa disease. An extended lymph node dissection plus or minus an extended liver resection should be performed in some patients with more advanced disease. However, there was no survival advantage to the more radical procedures, including bile duct resection or pancreaticoduodenectomy (1),(8). Owing to the strong association of gallstones with the disease, attempts should be made to convince the patients regarding the risks which are involved, to ensure an early cholecystectomy, moreso in patients with stones which are larger than 3 cm, who reside in a high-incidence area. A routine histopathological examination of all the cholecystectomy specimens is a must. The decision as to which therapeutic option should be used, depends on whether the carcinoma has been diagnosed pre-operatively, per-operatively or post-operatively, as well as on the stage of the disease – that is, whether it is localized resectable, localized unresectable or advanced disease. Any detection of unsuspected carcinoma in stage I following cholecystectomy needs only a meticulous follow-up. If the disease is detected in stage II, a radical cholecystectomy is required, and beyond this stage, an adjuvant therapy in the form of radiotherapy or chemotherapy or both is required, even though its role is not well elucidated (2),(18),(19).

The recommended surgical management of the stage I disease is simple cholecystectomy. We had two such patients in our study. Incidental carcinoma was detected in these patients following surgery for chronic cholecystitis by histopathology. The growth was restricted to the mucosa and the submucosa without involvement of the muscle layer. Hence, a simple cholecystectomy in these patients was curative. There was no need for re-exploration for an extended resection and a completion cholecystectomy. Two patients underwent an extended cholecystectomy with liver wedge resection. In the presence of ascites with or without liver metastasis, even the palliation of obstructive jaundice may not be possible (10),(11),(12),(13),(14),(15),(16),(17),(18). The 5 year survival correlates with the staging of the disease at the time of presentation. The survival rates of the disease in stages II, III and IV are approximately 25%, 12%, and 1-2% respectively (10),(11),(12),(13),(14),(15),(16). Among these, 32 patients succumbed to the disease within 6 months. The best prognosis was noted in patients with incidental carcinoma. Overall, the prognosis of the disease remained grim.

It is desirable to search for any factor which can be linked to the gall bladder cancer or that which can help in the diagnosis of the disease in its early stages, thus making a surgical intervention possible and ultimately resulting in a good prognosis. Moreover, to positively affect the outcome of the patients in the advanced stage of the disease, newer cancer treatment strategies need to be adopted.

Conclusion

We should accept the fact that gall bladder cancer is a disease with low numbers of patients who are amenable to surgery. Thus, instead of retrospectively analyzing the individual institutional data, high volume institutions with the necessary expertise for treating gall bladder cancer should collaborate with a view to generatinga strong evidence to support the different surgical strategies – a move that may provide us with the evidence-based surgical guidelines which we are looking for, to enable us better to tackle this dreadful disease.

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