discusses in detail about approach and management of HCC. Other liver masses and abscesses including cholangiocarcinoma. liver abscess, Hydatid cyst, Hepatic adenoma, hemangioma, Focal Nodular Hyperplasia.
discusses in detail about approach and management of HCC. Other liver masses and abscesses including cholangiocarcinoma. liver abscess, Hydatid cyst, Hepatic adenoma, hemangioma, Focal Nodular Hyperplasia.
Hepatocellular carcinoma—role of interventional radiologist Dr. Muhammad Bin ...Dr. Muhammad Bin Zulfiqar
In these presentation we will discuss the merits, demrits and outcomes of various interventional radiology modalities for the treatment of hepatocellular carcinoma
This Presentation gives summarized overview of Gall Bladder Carcinoma especially the management as per latest National Comprehensive Cancer Network(NCCN) Guidelines version 2.2013
Gall bladder carcinoma seen in Indian popluation most common in women and presents at a very late stage .Survival is in months hence palliative treatment is being preferred .
Hepatocellular carcinoma—role of interventional radiologist Dr. Muhammad Bin ...Dr. Muhammad Bin Zulfiqar
In these presentation we will discuss the merits, demrits and outcomes of various interventional radiology modalities for the treatment of hepatocellular carcinoma
This Presentation gives summarized overview of Gall Bladder Carcinoma especially the management as per latest National Comprehensive Cancer Network(NCCN) Guidelines version 2.2013
Gall bladder carcinoma seen in Indian popluation most common in women and presents at a very late stage .Survival is in months hence palliative treatment is being preferred .
(May 29th, 2024) Advancements in Intravital Microscopy- Insights for Preclini...Scintica Instrumentation
Intravital microscopy (IVM) is a powerful tool utilized to study cellular behavior over time and space in vivo. Much of our understanding of cell biology has been accomplished using various in vitro and ex vivo methods; however, these studies do not necessarily reflect the natural dynamics of biological processes. Unlike traditional cell culture or fixed tissue imaging, IVM allows for the ultra-fast high-resolution imaging of cellular processes over time and space and were studied in its natural environment. Real-time visualization of biological processes in the context of an intact organism helps maintain physiological relevance and provide insights into the progression of disease, response to treatments or developmental processes.
In this webinar we give an overview of advanced applications of the IVM system in preclinical research. IVIM technology is a provider of all-in-one intravital microscopy systems and solutions optimized for in vivo imaging of live animal models at sub-micron resolution. The system’s unique features and user-friendly software enables researchers to probe fast dynamic biological processes such as immune cell tracking, cell-cell interaction as well as vascularization and tumor metastasis with exceptional detail. This webinar will also give an overview of IVM being utilized in drug development, offering a view into the intricate interaction between drugs/nanoparticles and tissues in vivo and allows for the evaluation of therapeutic intervention in a variety of tissues and organs. This interdisciplinary collaboration continues to drive the advancements of novel therapeutic strategies.
Observation of Io’s Resurfacing via Plume Deposition Using Ground-based Adapt...Sérgio Sacani
Since volcanic activity was first discovered on Io from Voyager images in 1979, changes
on Io’s surface have been monitored from both spacecraft and ground-based telescopes.
Here, we present the highest spatial resolution images of Io ever obtained from a groundbased telescope. These images, acquired by the SHARK-VIS instrument on the Large
Binocular Telescope, show evidence of a major resurfacing event on Io’s trailing hemisphere. When compared to the most recent spacecraft images, the SHARK-VIS images
show that a plume deposit from a powerful eruption at Pillan Patera has covered part
of the long-lived Pele plume deposit. Although this type of resurfacing event may be common on Io, few have been detected due to the rarity of spacecraft visits and the previously low spatial resolution available from Earth-based telescopes. The SHARK-VIS instrument ushers in a new era of high resolution imaging of Io’s surface using adaptive
optics at visible wavelengths.
Seminar of U.V. Spectroscopy by SAMIR PANDASAMIR PANDA
Spectroscopy is a branch of science dealing the study of interaction of electromagnetic radiation with matter.
Ultraviolet-visible spectroscopy refers to absorption spectroscopy or reflect spectroscopy in the UV-VIS spectral region.
Ultraviolet-visible spectroscopy is an analytical method that can measure the amount of light received by the analyte.
THE IMPORTANCE OF MARTIAN ATMOSPHERE SAMPLE RETURN.Sérgio Sacani
The return of a sample of near-surface atmosphere from Mars would facilitate answers to several first-order science questions surrounding the formation and evolution of the planet. One of the important aspects of terrestrial planet formation in general is the role that primary atmospheres played in influencing the chemistry and structure of the planets and their antecedents. Studies of the martian atmosphere can be used to investigate the role of a primary atmosphere in its history. Atmosphere samples would also inform our understanding of the near-surface chemistry of the planet, and ultimately the prospects for life. High-precision isotopic analyses of constituent gases are needed to address these questions, requiring that the analyses are made on returned samples rather than in situ.
Multi-source connectivity as the driver of solar wind variability in the heli...Sérgio Sacani
The ambient solar wind that flls the heliosphere originates from multiple
sources in the solar corona and is highly structured. It is often described
as high-speed, relatively homogeneous, plasma streams from coronal
holes and slow-speed, highly variable, streams whose source regions are
under debate. A key goal of ESA/NASA’s Solar Orbiter mission is to identify
solar wind sources and understand what drives the complexity seen in the
heliosphere. By combining magnetic feld modelling and spectroscopic
techniques with high-resolution observations and measurements, we show
that the solar wind variability detected in situ by Solar Orbiter in March
2022 is driven by spatio-temporal changes in the magnetic connectivity to
multiple sources in the solar atmosphere. The magnetic feld footpoints
connected to the spacecraft moved from the boundaries of a coronal hole
to one active region (12961) and then across to another region (12957). This
is refected in the in situ measurements, which show the transition from fast
to highly Alfvénic then to slow solar wind that is disrupted by the arrival of
a coronal mass ejection. Our results describe solar wind variability at 0.5 au
but are applicable to near-Earth observatories.
Introduction:
RNA interference (RNAi) or Post-Transcriptional Gene Silencing (PTGS) is an important biological process for modulating eukaryotic gene expression.
It is highly conserved process of posttranscriptional gene silencing by which double stranded RNA (dsRNA) causes sequence-specific degradation of mRNA sequences.
dsRNA-induced gene silencing (RNAi) is reported in a wide range of eukaryotes ranging from worms, insects, mammals and plants.
This process mediates resistance to both endogenous parasitic and exogenous pathogenic nucleic acids, and regulates the expression of protein-coding genes.
What are small ncRNAs?
micro RNA (miRNA)
short interfering RNA (siRNA)
Properties of small non-coding RNA:
Involved in silencing mRNA transcripts.
Called “small” because they are usually only about 21-24 nucleotides long.
Synthesized by first cutting up longer precursor sequences (like the 61nt one that Lee discovered).
Silence an mRNA by base pairing with some sequence on the mRNA.
Discovery of siRNA?
The first small RNA:
In 1993 Rosalind Lee (Victor Ambros lab) was studying a non- coding gene in C. elegans, lin-4, that was involved in silencing of another gene, lin-14, at the appropriate time in the
development of the worm C. elegans.
Two small transcripts of lin-4 (22nt and 61nt) were found to be complementary to a sequence in the 3' UTR of lin-14.
Because lin-4 encoded no protein, she deduced that it must be these transcripts that are causing the silencing by RNA-RNA interactions.
Types of RNAi ( non coding RNA)
MiRNA
Length (23-25 nt)
Trans acting
Binds with target MRNA in mismatch
Translation inhibition
Si RNA
Length 21 nt.
Cis acting
Bind with target Mrna in perfect complementary sequence
Piwi-RNA
Length ; 25 to 36 nt.
Expressed in Germ Cells
Regulates trnasposomes activity
MECHANISM OF RNAI:
First the double-stranded RNA teams up with a protein complex named Dicer, which cuts the long RNA into short pieces.
Then another protein complex called RISC (RNA-induced silencing complex) discards one of the two RNA strands.
The RISC-docked, single-stranded RNA then pairs with the homologous mRNA and destroys it.
THE RISC COMPLEX:
RISC is large(>500kD) RNA multi- protein Binding complex which triggers MRNA degradation in response to MRNA
Unwinding of double stranded Si RNA by ATP independent Helicase
Active component of RISC is Ago proteins( ENDONUCLEASE) which cleave target MRNA.
DICER: endonuclease (RNase Family III)
Argonaute: Central Component of the RNA-Induced Silencing Complex (RISC)
One strand of the dsRNA produced by Dicer is retained in the RISC complex in association with Argonaute
ARGONAUTE PROTEIN :
1.PAZ(PIWI/Argonaute/ Zwille)- Recognition of target MRNA
2.PIWI (p-element induced wimpy Testis)- breaks Phosphodiester bond of mRNA.)RNAse H activity.
MiRNA:
The Double-stranded RNAs are naturally produced in eukaryotic cells during development, and they have a key role in regulating gene expression .
2. Introduction
• MC tumors of liver are metastatic tumors in liver
• Usually GIT tumors mostly metastasize through the portal venous route
• MC cancer metastasizing to liver is the CRC
• Other tumors metastasizing to liver include
• Upper GIT
• GUT
• Neuroendocrine
• Breast
• Eye
• Skin
• Soft tissue
• Gynecological malignancies
3. • Large majority of metastatic liver tumors that present with concomitant
extrahepatic disease will have unresectable liver disease and are not curable
with resection, limiting the role of surgeon to highly select cases requiring
operation.
•Metastatic adenocarcinoma to the liver of
unknown primary is often a primary IHC.
• Metastatic colorectal cancer isolated in the liver can be resected with the
potential for long-term survival and cure.
• Advances in systemic and regional chemotherapy have also broadened the
number of patients eligible for surgical therapy and improved long term
survival
• Selection of patients is the most important aspect of surgical therapy for
metastatic disease in the liver. A realistic expectation and honest patient
opinion is important.
4. COLORECTAL METASTASIS IN LIVER
• Up to 60% of CRC patients develop metastasis during the course of their illness.
• Among a large group of patients who develop metastasis, only few patients
develop CRC
• 2 types of growth seen
• Synchronous at the time of diagnosis of primary disease
[Synchronous is defined as the detection (by imaging) of suspicious liver metastases within 90
days before or after the date of histologic diagnosis of the primary colon or rectal cancer. ]
• Metachronous at > 1 year after the diagnosis of primary disease
• Synchronous liver metastasis portend to a worse prognosis that metachronous disease.
• Only 5-10% OF PATIENTS ARE CANDIDATES FOR POTENTIALLY CURATIVE LESION.
5.
6. Presentation of patients
• Symptoms of advanced malignancy
• Pain
• Ascites
• Jaundice
• Weight loss
• Palpable mass
• Patients who are carefully observed with serial P/E, cross-sectional
imaging studies, LFTs and determination of CEA levels are those
found to have resectable metachronous disease at the time of
diagnosis of primary CRC pre-operatively or during laparotomy
7. • A RISING CEA LEVEL ON SERIAL EXAMINATION AND NEW SOLID MASS ON
IMAGING STUDIES ARE DIAGNOSTIC OF METASTATIC DISEASE.
• LFT Rising GGT, ALP and LDH
• CT/ MRI Portal venous phase.
• WORKUP
• Colonoscopy (if > 1 year since primary CRC) to rule out recurrence/ metachronous
tumor
• CT abdomen/pelvis
• Chest CT
8. Management approach
• Surgical approach
• No trial for chemotherapy vs surgery
• Long term survival is extremely rare without treatment and is closely related to the
extent of disease
• Combination chemotherapy is now done along with surgery→ 5-FU+ Irinotecan
OR Oxaliplatin combined with antiangiogenic antibody→ Bevacizumab (anti-VEGF)
or Cetuximab (anti-epidermal growth factor) [ @ FI- BO-CO]
• 50% of patients undergoing a liver resection for metastatic colorectal cancer will
survive for 3 years and 20% will survive for 10 years.
• There is also significant morbidity rates of 30% to 50%.
• Complications
• Bleeding, bile leak, abscess and other generalized CVS complications.
9. Prognostic factors
The only contraindication for surgery NOW is inability to resect all disease.
Poor prognostic factors
• Extrahepatic metastasis
• LN involved with primary CRC
• Synchronous tumor
• Larger number of tumors
• Bilobar involvement
• CEA > 200 ng/ml
• Size of tumor > 5 cm
• Involved histologic margin
10. ● Hepatectomy for four or more metastasis is associated with approximate 5-
year survival of 33%.
● Attempt at least 1 cm wide margin when possible.
• Attempt extrahepatic metastasis resection along with liver metastasis in
following conditions
Limited lung metastasis
Locoregional recurrence
Portal lymph node
• Although long term survival after liver resection for CRC mets is common,
approx. overall 75% patients have recurrence in liver itself again
• After second liver resection, 5-survival falls to 30-40%
11. ● Adjuvant therapy
○ Adjuvant hepatic intra-arterial therapy has shown some benefit.
○ Adjuvant chemotherapy is independently a/w with OS and PFS.
EORTC 40983 trial
14. What if the tumor is unresectable?
• Pre-operative systemic and HAI chemotherapy may convert some
patients into resection candidates.
• Use of strategies like Parenchyma-preserving segmental
resections, two-staged operations, thermal ablation (Cryo, RFA, MW
ablation)
• Combination techniques Multiple bi-lobar tumors can be
extirpated by combination of resection and ablation with
preservation of hepatic parenchyma.
