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

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Dr Mohan Z Mani

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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.
Their prompt and timely response to review's query and the manner in which they have set the reviewing process helps in extracting the best possible scientific writings for publication.
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
Anuradha

Dear team JCDR, I would like to thank you for the very professional and polite service provided by everyone at JCDR. While i have been in the field of writing and editing for sometime, this has been my first attempt in publishing a scientific paper.Thank you for hand-holding me through the process.


Dr. Anuradha
E-mail: anuradha2nittur@gmail.com
On Jan 2020

Important Notice

Original article / research
Year : 2022 | Month : June | Volume : 16 | Issue : 6 | Page : TC01 - TC05 Full Version

Radiological Outcome of Subcentimeter Arterially Enhancing Nodules Detected during Surveillance for Hepatocellular Carcinoma- A Cohort Study


Published: June 1, 2022 | DOI: https://doi.org/10.7860/JCDR/2022/50489.16433
Prabhat Prakash Gupta, Nimisha Lohiya

1. Senior Resident, Department of Radiology, Medanta The Medicity Hospital, Gurugram, Haryana, India. 2. Senior Resident, Department of Radiology, ABVIMS and Dr RML Hospital, Delhi, Delhi, India.

Correspondence Address :
Prabhat Prakash Gupta,
123, Priya Enclave, Near Karkarduma Court, Delhi, Delhi, India.
E-mail: prabhatprakash@gmail.com

Abstract

Introduction: Hepatocellular Carcinoma (HCC) is the sixth most diagnosed cancer and the fourth leading cause of cancer-related death globally. The male: female ratio for HCC in India is 4:1 with age of presentation ranging from 40 to 70 years. There is limited clinical information on the course of Subcentimeter-Sized Nodules (SCSNs) detected during surveillance for HCC.

Aim: To evaluate the serial outcome of subcentimeter arterially enhancing nodules evolving into HCC and henceforth, to identify specific radiological features which can prognosticate and, if possible, predict which SCSNs will turn into HCC.

Materials and Methods: A prospective cohort study was conducted in a tertiary care center in Delhi NCR, in the Department of Radiodiagnosis between 1st May 2018 and 30th April 2019. Total of 72 lesions in 59 patients were evaluated during the study period of one year, which included images spanning over a mean duration of three years (range 2-6.5 years). Dynamic contrast enhanced imaging was done as per Liver Imaging Reporting and Data System version 2018 (LI-RADS version 2018) using either Magnetic Resonance Imaging (MRI) or Computed Tomography (CT). The gold standard for HCC diagnosis was LR 5 lesion. Size cut-off, rate of growth, enhancement features were studied and calculated. Student’s t-test was used for comparison of quantitative outcome parameters.

Results: A total of 59 patients were analysed with mean age 53±12 years, of which 85% were males. The cumulative HCC development rate was 47.5%. A 60.9% of the SCSNs which turned into HCCs showed an increase in size, 31.6% of the non HCC-SCSN lesions also showed an increase in size. Upon baseline comparison, the growth difference was more in the HCC group (8.2±12.24 mm) than in the non HCC group (3.37±7.39 mm). The optimal cut-off points after which the likelihood of an arterially enhancing lesion turning into HCC increased significantly was 8.5 mm on CT and 10.5 mm on MRI.

Conclusion: Around 47.5% of arterially enhancing SCSN converted into HCC; this percentage is much higher than quoted literature. A six monthly follow-up may be considered as 52.2 percent of lesions turned into HCC in a span of 1 year. The optimal cut-off points after which the likelihood of an arterially enhancing lesion turning into HCC increases can be taken as 8.55 mm on CT and 10.5 mm on MRI. Among the lesions showing washout, 80.8 % on CT and 91.3% nodules on MRI changed into HCC.

Keywords

Computed tomography, Diffusion restriction, Hepatobiliary contrast, Magnetic resonance imaging, Washout

The HCC is the sixth most diagnosed malignancy and the fourth leading cause of cancer-related death globally (1). In India, the age adjusted incidence rate of HCC ranges from 0.7 to 7.5 and 0.2 to 2.2 per 100,000 of population per year for men and women respectively. The male: female ratio for HCC in India is 4:1 with age of presentation ranging from 40 to 70 years (2).

The most reliable diagnostic examinations for diagnosis of HCC are multiphasic CT and MRI, which includes late arterial, portal venous, hepatic venous, and delayed/equilibrium phase imaging at about 3-5 minutes after contrast injection(3),(4). The presence of arterial enhancement followed by washout has a sensitivity of 90%, specificity of 95%, and a positive predictive value of approximately 100% among the group having high chances of developing HCC, e.g., cirrhotics (5). Washout is defined by the appearance of a hypoattenuating area in the portovenous or delayed phase on a triphasic CT liver scan that was hyperdense compared with the rest of the liver in the arterial phase (6).

Hepatobiliary contrast agents are extracellular gadolinium chelates that are now routinely employed in MR liver scanning. Apart from renal excretion, these agents also have a component excreted by the liver depending upon the functional hepatocytes in the parenchyma. A significant benefit of these agents is that they can detect early HCC that shows relative hypoenhancement on the Hepatobiliary Phase (HBP) when there is no appreciable arterial enhancement or venous washout. This can increase the sensitivity and accuracy for HCC diagnosis (7),(8). HBP hypointensity favours a premalignant or a malignant lesion rather than a low-grade dysplastic or a cirrhotic nodule in studies with hepatitis B and C patients (9),(10).

Diffusion-Weighted Imaging (DWI) can enhance the diagnostic performance of MRI for small HCCs by demonstrating higher cellularity of HCCs. Other ancillary imaging features favouring HCC diagnosis include the presence of intralesional fat, mild to modest hyperintensity on T2-weighted images, and morphologic findings such as intratumoural haemorrhage, fatty transformation, and nodule-in-nodule configuration (11).

Accordingly, the European Association for the Study of the Liver and the American Association for the Study of Liver Diseases advocate performing screening for HCC in patients at risk. There are imaging criteria for HCC diagnosis if lesions are 1 cm or larger, but a wait and watch policy is recommended for nodules smaller than 1 cm owing to a high false positive rate. However, there is a high possibility that minute hepatic nodules detected during surveillance may become malignant over time (12),(13),(14). Nevertheless, there is limited information on the clinical course of SCSNs detected during surveillance.

Arterially enhancing lesions are mostly benign and include primary liver tumours like focal nodular hyperplasia, adenoma, and small hemangiomas that rapidly fill with contrast. These have to be differentiated from the most common hypervascular malignant liver tumour, which is HCC; and metastasis from hypervascular neoplasms like melanoma, renal cell carcinoma, breast, sarcoma and neuroendocrine tumours (carcinoid, pheochromocytoma, islet cell tumours).

Meanwhile, according to the LI-RADS classification, which endorses a conservative approach, even though a definitive diagnosis of HCC cannot be established, “probable” HCC can be given for subcentimeter nodules showing one finding among “threshold growth,” “washout,” or “capsule,” (15). Korean Liver Cancer Study Group-National Cancer Center (KLCSG-NCC) practice guidelines suggests that HCCs can be diagnosed by a combination of the typical features of HCCs in ?2 imaging modalities and increased serum ?-fetoprotein levels with an increasing trend over time for liver nodules <1 cm in patients with suppressed hepatitis activity (16).

The diagnosis of subcentimeter HCC can be clinically helpful by providing two different options, i.e., immediate treatment and intense follow-up. The key to achieving long-term survival is promptly implementing effective treatment strategies, including locoregional ablative therapy, hepatic resection, and liver transplantation (17),(18).

Therefore, the current evidence is not concrete in discretely triaging subcentimeter hypervascular nodules in the cirrhotic liver. Also, there is no data from the Indian subcontinent. Furthermore, the rate of growth of SCSN and imaging predictive markers of hypervascular SCSN, which turn into HCC, is also not clear.

This study aimed to evaluate the incidence of arterially enhancing subcentimeter nodules evolving into HCC. To identify any specific size cut-off, rate of growth, or specific radiologic features which can prognosticate and, if possible, predict which subcentimeter arterially enhancing nodule will turn into HCC.

Material and Methods

A prospective observational cohort study was conducted in all cirrhotic patients who presented to the Department of Radiodiagnosis at Medanta The Medicity, Gurgaon Haryana, India, for dynamic CT or MRI during the study period from (1st May 2018 to 30th April 2019) The study was undertaken only after the approval from Institutional Review Board.

Inclusion criteria: Patients with liver cirrhosis of any aetiology or chronic liver disease, including chronic hepatitis B and C viral infection, without a prior history of HCC in whom a SCSN was identified during HCC surveillance with either CT or MRI were included.

Exclusion criteria: Patients with lesions size more than 1 cm or known HCC on the first scan were excluded from the analysis. Also, patients who had only a single imaging study were eliminated from the research group.

Sample size calculation: Cochran formula was used for sample size calculation which yielded a minimum number of 51 lesions (19). The final study was done on 72 lesions in 59 patients.

After the inclusion in the study, the patients were further followed for at least one year. The retrospective previous cross-sectional imaging, if available, was also included in the study.

LI-RADS is a system to categorise liver lesions used in patients with liver cirrhosis and chronic hepatitis B without cirrhosis, as these patients are at an increased risk of HCC. LI-RADS staging reflects the probability of HCC and is based on the typical CT and MRI findings in HCC. LI-RADS is currently not to be used in patients <18 years or patients with cirrhosis due to other causes like congenital hepatic fibrosis or vascular disorders. This is because these patients have lower chances of developing HCC (20).

Imaging Analysis

The multiphasic imaging was done in-house CT and MRI scanners:

1. Siemens Somatom Definition Flash- 128 dual source MDCT scanner (Siemens Healthineers, Erlangen, Germany).
2. Siemens Magnetom Verio-3 Tesla (Siemens Healthineers, Erlangen, Germany).

Scans were independently and retrospectively reviewed on a Picture Archiving and Communication System workstation by two Radiologists with more than 10 years’ experience in hepatobiliary imaging, who evaluated the lesions at different time points for above criteria on dynamic CT and MRI. A definitive interobserver disagreement between the assessors, which occurred in 7 cases, required consensus of the radiology team.

The gold standard for HCC diagnosis was LR 5 lesion. An LR 5 lesion is more than 20 mm in size, showing arterial phase hyperenhancement and washout on portovenous phases/enhancing capsule/threshold growth.

The findings were collected in a tabulated form. The following outcomes were assessed: percentage of lesions turning into HCC, size specific cut-off, rate of conversion, and imaging criteria suspicious for HCC.

Statistical Analysis

The analysis involved profiling of patients on different demographic, clinical and radiological findings. Quantitative data sets were presented in terms of means and standard deviation. Qualitative/categorical data were presented as absolute numbers and proportions. Crosstables were constructed and Chi-square test was used for testing of association. Student’s t-test was used for comparing quantitative parameters. The Area Under the Curve (AUC) was measured using ROC curve analysis. The cut of points has been calculated as a minimum of (1-Sensitivity)2 + (1 - Specificity)2. The cut-off values along with corresponding sensitivity & specificity was also calculated. The p-value <0.05 was considered statistically significant. Statistical Package for Social Sciences (SPSS) software version 20.0 was used for statistical analysis.

Results

A total of 59 patients were analysed, of which 85% were males, and 15% were females between ages of 22 to 81 (Mean± standard deviation: 53±12 years). Many of the patients were scanned using both modalities at different time points. Out of 59 patients, 96.6% (n=57) underwent CT examination and 71.2% (n=42) were scanned using MRI. Out of 59 patients, 28 (47.5%) developed HCC during the study period.

Of those who developed HCC, 74.1 % had an increase in size on CT. With MRI as an imaging modality, 58.3% of the HCC lesions showed an increase in size while only 33.3% of the non HCC lesions increased in size (Table/Fig 1).

The nodules’ mean size, when labeled as HCC, was 13.6±15 mm on CT and 18.1±11.8 mm on MRI.

Upon baseline comparison, the growth difference was more in the HCC group (8.2±12.24 mm) than in the non HCC group (3.37±7.39 mm). None of the lesions turning into HCC showed a decrease in size.

There was a substantial increase in size in the nodules that later evolved into HCC compared with nodules that did not. Using CT as an investigation modality, the mean size of an arterially enhancing SCSN at first scanning, which later turned into HCC, was 5.0±3.5 mm, while which did not turn into HCC was 5.4±3.4 mm. Upon continuous follow-up, the lesions that ultimately transformed into HCC had a difference in growth size between first and last CT was of 8.4±14.0 mm vis a vis non HCC group, which had a growth of 1.4±3.6 mm with a p-value of 0.011, which was statistically significant.

The optimal cut-off points after which the likelihood of an arterially enhancing lesion turning into HCC increase was 8.5 mm in CT with a sensitivity of 72.7 % and a specificity of 66.7% (AUC 0.741); and 10.5 mm in MRI with a sensitivity of 77.3 % and a specificity of 66.7% (AUC 0.749) (Table/Fig 2).

Washout was demonstrated in 40.4% of the lesions on CT scan and 50% on MRI scan. Of these, almost 80.8 % of nodules on CT and 87.5% on MRI changed into HCC (p-value <0.001), which is statistically significant (Table/Fig 3).

In patients having nodules that later changed into HCC and were scanned using MRI, 45.8% showed diffusion restriction (p-value 0.002), and 83.3% demonstrated non uptake of hepatobiliary contrast (p-value <0.001), which was statistically significant (Table/Fig 4).

For arterially enhancing SCSN, the mean HCC free interval was 3.3 years and the median HCC free interval was 2.1 years. At a time interval of 1 year, 47.8% of lesions did not change into HCC and at an interval of 4 years, 45.2% of lesions did not convert into malignancy. (The retrospective previous cross-sectional imaging, if available, was also considered in the study. Some of the included patients had previous imaging reaching upto,4-6 years, so their 4 years’ worth of investigation and imaging was included in the study).

Discussion

In our study, the incidence of development of HCC was 47.5 % from arterially enhancing subcentimeter nodules, with upto 52.2% of lesions changing into HCC within the first year. This percentage is relatively higher than the reported literature; a plausible explanation for this could be the inclusion of cirrhotics or patients of chronic liver disease due to any aetiology rather than patients only of hepatitis B or C virus infection. In the study by Min YW et al., the yearly incidence was 4.9% for the development of HCC from nodules in patients with chronic hepatitis B or C infection (12). Other researchers have also reported a similar incidence of 2-8% for subcentimeter nodules changing into HCC within a year, in patients with chronic hepatitis B or C infection (13),(21). Park MJ et al., reported that small (5-10 mm) arterially enhancing nodules on CT in surveillance for HCC have a 29.5% probability of developing into HCC over a mean 35.7 month of follow-up (22). According to a study by Forner A et al., 15.4% of subcentimeter lesions turned into HCC over a median follow-up period ranging from 23-30 months (23). Jeong YY et al., reported that 13% of arterial enhancing nodules less than 2 cm were HCC in patients with cirrhosis (24). Holland AE et al., who evaluated 45 arterial phase enhancing nodules smaller than 2 cm in cirrhotic livers, found that 35% of patients with cirrhosis had these enhancing nodules and that only 7% of lesions were neoplastic (25). There is wide variation in the current cited literature regarding subcentimeter nodules’ incidence of evolving to malignancy. Still, it is coherent to consider that arterially enhancing lesions show a higher propensity to convert into HCC, as demonstrated in the present study (Table/Fig 5).

The optimal time for follow-up of the patient should be every six months as upto 52.2% of lesions might convert into HCC within one year. Also, lesions can convert into HCC even after remaining stable for 3-4 years. Therefore, hypervascular lesions should be followed-up for at least 6 years (12). Min YW et al., recommended follow-up of SCSNs every few months to detect growth suggestive of malignant transformation (12).

Song KD et al., reported that the initial size of hypervascular SCSN was a significant predictor of progression to overt HCC, with a cut-off value of 5.5 mm (26). As per his findings, most SCSNs (89.9 %) progressed to overt HCCs within 12 months, and all SCSNs larger than 5.5 mm, progressed to overt HCCs within 12 months. Our statistical analysis revealed that the optimal cut-off points after which the likelihood of an arterially enhancing lesion turning into HCC increased was 8.5 mm in CT and 10.5 mm in MRI. So, it concurred that once the lesion nears these cut-off points, they need to be more aggressively followed-up. In addition, in this study, the rate of change of size was a better predictor than baseline size for predicting LR 5 HCC on CT.

In current study, none of the lesions that changed into HCC decreased in size. Of the nodules that changed into HCC over time, only 23.1% on CT and 25% on MRI showed rim enhancement (Table/Fig 6). This is partially explained because when the tumours become 1.5 to 2 cm in diameter, they tend to dedifferentiate, becoming moderately differentiated and growing in an expansile fashion with the formation of a fibrous capsule (27). A surrounding tumour capsule can be detected in lesions of any size, but because of increasing capsule thickness with increasing tumour size, capsules are better seen with bigger HCCs (28). They are typically thin and discontinuous and show progressive delayed enhancement. Capsular enhancement may represent contrast material retained in the fibrous and vascular elements of the tumour margin (29). Capsular enhancement is seldom seen in tumours less than 1 cm in diameter (30). Ishigami K et al., noted that HCCs with histologic fibrous capsules were larger than 1.2 cm in size and that approximately one-half of well-differentiated HCCs had no enhancing capsule (31).

DWI may improve the diagnostic performance of MRI for malignant SCSNs by demonstrating higher cellularity of HCC (11). In this study, 45.8% of small HCCs had restricted diffusion (Table/Fig 6). Albin N et al., elucidated that on DWI, 79% of dysplastic nodules are iso- or hypointense, whereas 97% of HCCs are hyperintense (32).

HBP hypointensity is a strong indicator of premalignancy or malignancy, and its presence favours early HCC over a cirrhotic nodule (10). Out of all who developed HCC, 83.3% of patients showed HBP hypointensity, which was statistically significant (p-value <0.001).

Limitation(s)

The present study had some limitations. There was a lack of histologic confirmation for the lesions, which were defined on the basis of radiologic images. However, it is unlikely that HCCs were mistakenly categorised, as previous imaging was also considered. Additionaly, pathological validation of these lesions would not be practical in routine clinical settings. Lastly, our assessments regarding the number, nodule pattern, location, and size of SCSNs had a component of subjectivity due to the small nodule sizes and sometimes ill-defined margins. To overcome this limitation, all radiologic images were reviewed by two experienced radiologists. Future large multi-center prospective studies are needed to refine our research findings and confirm our proposed cut-off values.

Conclusion

Thus, around 47.1% of subcentimeter arterially enhancing nodules have the potential to turn into HCC. The size specific cut-off for CT was 8.5 mm, and for MRI was 10.5 mm with a sensitivity of 72.7% and 77.3%. The optimal time for following-up the patient should be every six months as upto 52.2 % of lesions might turn into HCC in less than one year. None of the lesions that changed into HCC decreased in size on imaging. Diffusion restriction and HBP hypointensity are strong predictors of premalignancy or malignancy, and their presence favours early HCC over cirrhotic nodule. This study can be used to power other large multicentric trials with larger sample sizes to further develop recommendations for subcentimeter arterially enhancing nodules in HCC surveillance.

References

1.
Rawla P, Sunkara T, Muralidharan P, Raj JP. Update in global trends and aetiology of hepatocellular carcinoma. Contemp Oncol. 2018;22(3):141-50. [crossref] [PubMed]
2.
Acharya SK. Epidemiology of Hepatocellular Carcinoma in India. J Clin Exp Hepatol. 2014;4(Suppl 3):S27-33. [crossref] [PubMed]
3.
Goshima S, Kanematsu M, Kondo H, Yokoyama R, Miyoshi T, Nishibori H, et al. MDCT of the liver and hypervascular hepatocellular carcinomas: optimizing scan delays for bolus-tracking techniques of hepatic arterial and portal venous phases. Am J Roentgenol. 2006;187(1):W25-32. [crossref] [PubMed]
4.
Kim M-J, Choi JY, Lim JS, Kim JY, Kim JH, Oh YT, et al. Optimal scan window for detection of hypervascular hepatocellular carcinomas during MDCT examination. Am J Roentgenol. 2006;187(1):198-206. [crossref] [PubMed]
5.
Omata M, Cheng A-L, Kokudo N, Kudo M, Lee JM, Jia J, et al. Asia-Pacific clinical practice guidelines on the management of hepatocellular carcinoma: a 2017 update. Hepatol Int. 2017;11(4):317-70. [crossref] [PubMed]
6.
Sherman M. Diagnosis of small hepatocellular carcinoma. Hepatology. 2005;42(1):14-16. [crossref] [PubMed]
7.
Granito A, Galassi M, Piscaglia F, Romanini L, Lucidi V, Renzulli M, et al. Impact of gadoxetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance on the non-invasive diagnosis of small hepatocellular carcinoma: a prospective study. Aliment Pharmacol Ther. 2013;37(3):355-63. [crossref] [PubMed]
8.
Hyodo T, Murakami T, Imai Y, Okada M, Hori M, Kagawa Y, et al. Hypovascular nodules in patients with chronic liver disease: risk factors for development of hypervascular hepatocellular carcinoma. Radiology. 2013;266(2):480-90. [crossref] [PubMed]
9.
Gatto A, De Gaetano AM, Giuga M, Ciresa M, Siciliani L, Miele L, et al. Differentiating hepatocellular carcinoma from dysplastic nodules at gadobenate dimeglumine-enhanced hepatobiliary-phase magnetic resonance imaging. Abdom Imaging. 2013;38(4):736-44. [crossref] [PubMed]
10.
Golfieri R, Grazioli L, Orlando E, Dormi A, Lucidi V, Corcioni B, et al. Which is the best MRI marker of malignancy for atypical cirrhotic nodules: hypointensity in hepatobiliary phase alone or combined with other features? Classification after Gd-EOB-DTPA administration. J Magn Reson Imaging JMRI. 2012;36(3):648-57. [crossref] [PubMed]
11.
Matsui O, Kadoya M, Kameyama T, Yoshikawa J, Arai K, Gabata T, et al. Adenomatous hyperplastic nodules in the cirrhotic liver: differentiation from hepatocellular carcinoma with MR imaging. Radiology. 1989;173(1):123-26. [crossref] [PubMed]
12.
Min YW. Clinical course of sub-centimeter-sized nodules detected during surveillance for hepatocellular carcinoma. World J Gastroenterol. 2012;18(21):2654. [crossref] [PubMed]
13.
Bruix J, Sherman M, Llovet JM, Beaugrand M, Lencioni R, Burroughs AK, et al. Clinical Management of Hepatocellular Carcinoma. Conclusions of the Barcelona-2000 EASL Conference. J Hepatol. 2001;35(3):421-30. [crossref]
14.
Bruix J, Sherman M. Management of hepatocellular carcinoma: an update. Hepatol Baltim Md. 2011;53(3):1020-22. [crossref] [PubMed]
15.
Elsayes KM, Hooker JC, Agrons MM, Kielar AZ, Tang A, Fowler KJ, et al. 2017 Version of LI-RADS for CT and MR Imaging: An Update. RadioGraphics. 2017;37(7):1994-2017. [crossref] [PubMed]
16.
Lee JM, Park J-W, Choi BI. 2014 KLCSG-NCC Korea Practice Guidelines for the management of hepatocellular carcinoma: HCC diagnostic algorithm. Dig Dis. 2014;32(6):764-77. [crossref] [PubMed]
17.
Parkin DM, Bray F, Ferlay J, Pisani P. Global cancer statistics, 2002. CA Cancer J Clin. 2005;55(2):74-108. [crossref] [PubMed]
18.
Altekruse SF, McGlynn KA, Reichman ME. Hepatocellular carcinoma incidence, mortality, and survival trends in the United States from 1975 to 2005. J Clin Oncol Off J Am Soc Clin Oncol. 2009;27(9):1485-91. [crossref] [PubMed]
19.
Cochran WG. Sampling techniques. 3d ed. New York: Wiley; 1977. 428 Pp. (Wiley series in probability and mathematical statistics).
20.
Chernyak V, Fowler KJ, Kamaya A, Kielar AZ, Elsayes KM, Bashir MR, et al. Liver Imaging Reporting and Data System (LI-RADS) Version 2018: imaging of hepatocellular carcinoma in at-risk patients. Radiology. 2018;289(3):816-30. [crossref] [PubMed]
21.
Degos F, Christidis C, Ganne-Carrie N, Farmachidi J, Degott C, Guettier C, et al. Hepatitis C virus related cirrhosis: time to occurrence of hepatocellular carcinoma and death. Gut. 2000;47(1):131-36. [crossref] [PubMed]
22.
Park MJ, Kim Y, Lee WJ, Lim HK, Rhim H, Lee J. Outcomes of follow-up CT for small (5-10-mm) arterially enhancing nodules in the liver and risk factors for developing hepatocellular carcinoma in a surveillance population. Eur Radiol. 2010;20(10):2397-404. [crossref] [PubMed]
23.
Forner A, Vilana R, Ayuso C, Bianchi L, Solé M, Ayuso JR, et al. Diagnosis of hepatic nodules 20 mm or smaller in cirrhosis: Prospective validation of the noninvasive diagnostic criteria for hepatocellular carcinoma. Hepatol Baltim Md. 2008;47(1):97-104. [crossref] [PubMed]
24.
Jeong YY, Mitchell DG, Kamishima T. Small (<20 mm) Enhancing Hepatic Nodules Seen on Arterial Phase MR Imaging of the Cirrhotic Liver: Clinical Implications. Am J Roentgenol. 2002;178(6):1327-34. [crossref] [PubMed]
25.
Holland AE, Hecht EM, Hahn WY, Kim DC, Babb JS, Lee VS, et al. Importance of small (≤20-mm) enhancing lesions seen only during the hepatic arterial phase at MR imaging of the cirrhotic liver: evaluation and comparison with whole explanted liver. Radiology. 2005;237(3):938-44. [crossref] [PubMed]
26.
Song KD, Kim SH, Lim HK, Jung S-H, Sohn I, Kim HS. Subcentimeter hypervascular nodule with typical imaging findings of hepatocellular carcinoma in patients with history of hepatocellular carcinoma: natural course on serial gadoxetic acid-enhanced MRI and diffusion-weighted imaging. Eur Radiol. 2015;25(9):2789-96. [crossref] [PubMed]
27.
Kutami R, Nakashima Y, Nakashima O, Shiota K, Kojiro M. Pathomorphologic study on the mechanism of fatty change in small hepatocellular carcinoma of humans. J Hepatol. 2000;33(2):282-89. [crossref]
28.
Murakami T, Tsurusaki M. Hypervascular benign and malignant liver tumours that require differentiation from hepatocellular carcinoma: key points of imaging diagnosis. Liver Cancer. 2014;3(2):85-96. [crossref] [PubMed]
29.
Grazioli L, Olivetti L, Fugazzola C, Benetti A, Stanga C, Dettori E, et al. The pseudocapsule in hepatocellular carcinoma: correlation between dynamic MR imaging and pathology. Eur Radiol. 1999;9(1):62-67. [crossref] [PubMed]
30.
Choi BI, Takayasu K, Han MC. Small hepatocellular carcinomas and associated nodular lesions of the liver: pathology, pathogenesis, and imaging findings. Am J Roentgenol. 1993;160(6):1177-87. [crossref] [PubMed]
31.
Ishigami K, Yoshimitsu K, Nishihara Y, Irie H, Asayama Y, Tajima T, et al. Hepatocellular Carcinoma with a Pseudocapsule on Gadolinium-enhanced MR Images: Correlation with Histopathologic Findings. Radiology. 2009;250(2):435-43. [crossref] [PubMed]
32.
Albiin N. MRI of focal liver lesions. Curr Med Imaging Rev. 2012;8(2):107-16. [crossref] [PubMed]

DOI and Others

DOI: 10.7860/JCDR/2022/50489.16433

Date of Submission: May 24, 2021
Date of Peer Review: Aug 15, 2021
Date of Acceptance: Feb 15, 2022
Date of Publishing: Jun 01, 2022

AUTHOR DECLARATION:
• Financial or Other Competing Interests: None
• Was Ethics Committee Approval obtained for this study? Yes
• Was informed consent obtained from the subjects involved in the study? Yes
• For any images presented appropriate consent has been obtained from the subjects. Yes

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