HCC [Hepatocellular carcinoma] needs either liver resection or liver transplant. Liver transplant in HCC is challenging in view of underlying cirrhosis as well as long waiting time for organ donors. Once HCC patient is kept on waiting list for organ donation, there is a high risk of tumor progression beyond liver transplant eligibility criteria. Such patients need bridging therapy for the control of tumour while they are on waitlist for organ donor. These bridging therapy helps to prevent tumour progression as well as down staging them to within the transplant criteria. Timing & method of bridging therapy for HCC patients on waitlist is critical in management of such patients.
Systemic treatment in advanced hepatocellular carcinoma (HCC) refers to the use of medications or therapies that are administered throughout the body to target cancer cells beyond the liver. HCC is the most common type of liver cancer and often presents at an advanced stage, making systemic therapies crucial in managing the disease.
One of the main categories of systemic treatment for advanced HCC is targeted therapies. Targeted therapies are designed to selectively inhibit specific molecules or pathways involved in tumor growth, thereby blocking the signals that support cancer cell survival and proliferation. Sorafenib and lenvatinib are examples of targeted therapies that have been approved for the first-line treatment of advanced HCC. They target vascular endothelial growth factor (VEGF) receptors, which play a key role in promoting the growth of new blood vessels necessary for tumor growth. By inhibiting these receptors, these drugs can help slow down tumor growth and improve patient outcomes.
In addition to sorafenib and lenvatinib, other targeted therapies have shown promising results in the treatment of advanced HCC. Regorafenib, for instance, is a multi-kinase inhibitor that targets several pathways involved in tumor angiogenesis, cell proliferation, and survival. Cabozantinib is another multi-kinase inhibitor that has been approved as a second-line treatment option for patients who have progressed on or are intolerant to prior systemic therapy. These targeted therapies have demonstrated efficacy in improving overall survival and delaying disease progression in patients with advanced HCC.
Another significant advancement in systemic treatment for advanced HCC is the use of immune checkpoint inhibitors. Immunotherapy has revolutionized cancer treatment in recent years, including for HCC. Immune checkpoint inhibitors, such as nivolumab and pembrolizumab, work by blocking proteins that act as checkpoints on immune cells, such as programmed cell death protein 1 (PD-1) or its ligand (PD-L1). By doing so, these drugs help restore and enhance the immune system's ability to recognize and eliminate cancer cells. Checkpoint inhibitors have shown promising results, with some patients experiencing durable responses and improved overall survival.
Systemic treatment in advanced hepatocellular carcinoma (HCC) refers to the use of medications or therapies that are administered throughout the body to target cancer cells beyond the liver. HCC is the most common type of liver cancer and often presents at an advanced stage, making systemic therapies crucial in managing the disease.
One of the main categories of systemic treatment for advanced HCC is targeted therapies. Targeted therapies are designed to selectively inhibit specific molecules or pathways involved in tumor growth, thereby blocking the signals that support cancer cell survival and proliferation. Sorafenib and lenvatinib are examples of targeted therapies that have been approved for the first-line treatment of advanced HCC. They target vascular endothelial growth factor (VEGF) receptors, which play a key role in promoting the growth of new blood vessels necessary for tumor growth. By inhibiting these receptors, these drugs can help slow down tumor growth and improve patient outcomes.
In addition to sorafenib and lenvatinib, other targeted therapies have shown promising results in the treatment of advanced HCC. Regorafenib, for instance, is a multi-kinase inhibitor that targets several pathways involved in tumor angiogenesis, cell proliferation, and survival. Cabozantinib is another multi-kinase inhibitor that has been approved as a second-line treatment option for patients who have progressed on or are intolerant to prior systemic therapy. These targeted therapies have demonstrated efficacy in improving overall survival and delaying disease progression in patients with advanced HCC.
Another significant advancement in systemic treatment for advanced HCC is the use of immune checkpoint inhibitors. Immunotherapy has revolutionized cancer treatment in recent years, including for HCC. Immune checkpoint inhibitors, such as nivolumab and pembrolizumab, work by blocking proteins that act as checkpoints on immune cells, such as programmed cell death protein 1 (PD-1) or its ligand (PD-L1). By doing so, these drugs help restore and enhance the immune system's ability to recognize and eliminate cancer cells. Checkpoint inhibitors have shown promising results, with some patients experiencing durable responses and improved overall survival.
CyberKnife is an option in inoperable or medically not suitable for surgery
& in patient with progression / not tolerating systemic therapy
- Initial results are impressive with low toxicity, good response rate
Pts with small tumour, no prior treatment with good performance
treated with high dose have significantly better survival
Dose >45 Gy; 15Gy/# and small vol tumour (<50cc) have better prognosis
There is minimal toxicity with CyberKnife in liver tumours
Addition of chemotherapy along with CyberKnife will be the future
Highlights in the treatment of Rectal cancer.pptxMona Quenawy
rectal cancer treatment updates in simple way and the advances in the molecular techniques .the role of the neo adjuvant chemoradiotherapy and the state of the art in the management by each stage.radiotherapy role and technique by using the RTOG guidance in target definition
CyberKnife is an option in inoperable or medically not suitable for surgery
& in patient with progression / not tolerating systemic therapy
- Initial results are impressive with low toxicity, good response rate
Pts with small tumour, no prior treatment with good performance
treated with high dose have significantly better survival
Dose >45 Gy; 15Gy/# and small vol tumour (<50cc) have better prognosis
There is minimal toxicity with CyberKnife in liver tumours
Addition of chemotherapy along with CyberKnife will be the future
Highlights in the treatment of Rectal cancer.pptxMona Quenawy
rectal cancer treatment updates in simple way and the advances in the molecular techniques .the role of the neo adjuvant chemoradiotherapy and the state of the art in the management by each stage.radiotherapy role and technique by using the RTOG guidance in target definition
New Drug Discovery and Development .....NEHA GUPTA
The "New Drug Discovery and Development" process involves the identification, design, testing, and manufacturing of novel pharmaceutical compounds with the aim of introducing new and improved treatments for various medical conditions. This comprehensive endeavor encompasses various stages, including target identification, preclinical studies, clinical trials, regulatory approval, and post-market surveillance. It involves multidisciplinary collaboration among scientists, researchers, clinicians, regulatory experts, and pharmaceutical companies to bring innovative therapies to market and address unmet medical needs.
Adv. biopharm. APPLICATION OF PHARMACOKINETICS : TARGETED DRUG DELIVERY SYSTEMSAkankshaAshtankar
MIP 201T & MPH 202T
ADVANCED BIOPHARMACEUTICS & PHARMACOKINETICS : UNIT 5
APPLICATION OF PHARMACOKINETICS : TARGETED DRUG DELIVERY SYSTEMS By - AKANKSHA ASHTANKAR
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Ve...kevinkariuki227
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
ARTIFICIAL INTELLIGENCE IN HEALTHCARE.pdfAnujkumaranit
Artificial intelligence (AI) refers to the simulation of human intelligence processes by machines, especially computer systems. It encompasses tasks such as learning, reasoning, problem-solving, perception, and language understanding. AI technologies are revolutionizing various fields, from healthcare to finance, by enabling machines to perform tasks that typically require human intelligence.
These simplified slides by Dr. Sidra Arshad present an overview of the non-respiratory functions of the respiratory tract.
Learning objectives:
1. Enlist the non-respiratory functions of the respiratory tract
2. Briefly explain how these functions are carried out
3. Discuss the significance of dead space
4. Differentiate between minute ventilation and alveolar ventilation
5. Describe the cough and sneeze reflexes
Study Resources:
1. Chapter 39, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 34, Ganong’s Review of Medical Physiology, 26th edition
3. Chapter 17, Human Physiology by Lauralee Sherwood, 9th edition
4. Non-respiratory functions of the lungs https://academic.oup.com/bjaed/article/13/3/98/278874
micro teaching on communication m.sc nursing.pdfAnurag Sharma
Microteaching is a unique model of practice teaching. It is a viable instrument for the. desired change in the teaching behavior or the behavior potential which, in specified types of real. classroom situations, tends to facilitate the achievement of specified types of objectives.
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Tom Selleck Health: A Comprehensive Look at the Iconic Actor’s Wellness Journeygreendigital
Tom Selleck, an enduring figure in Hollywood. has captivated audiences for decades with his rugged charm, iconic moustache. and memorable roles in television and film. From his breakout role as Thomas Magnum in Magnum P.I. to his current portrayal of Frank Reagan in Blue Bloods. Selleck's career has spanned over 50 years. But beyond his professional achievements. fans have often been curious about Tom Selleck Health. especially as he has aged in the public eye.
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Introduction
Many have been interested in Tom Selleck health. not only because of his enduring presence on screen but also because of the challenges. and lifestyle choices he has faced and made over the years. This article delves into the various aspects of Tom Selleck health. exploring his fitness regimen, diet, mental health. and the challenges he has encountered as he ages. We'll look at how he maintains his well-being. the health issues he has faced, and his approach to ageing .
Early Life and Career
Childhood and Athletic Beginnings
Tom Selleck was born on January 29, 1945, in Detroit, Michigan, and grew up in Sherman Oaks, California. From an early age, he was involved in sports, particularly basketball. which played a significant role in his physical development. His athletic pursuits continued into college. where he attended the University of Southern California (USC) on a basketball scholarship. This early involvement in sports laid a strong foundation for his physical health and disciplined lifestyle.
Transition to Acting
Selleck's transition from an athlete to an actor came with its physical demands. His first significant role in "Magnum P.I." required him to perform various stunts and maintain a fit appearance. This role, which he played from 1980 to 1988. necessitated a rigorous fitness routine to meet the show's demands. setting the stage for his long-term commitment to health and wellness.
Fitness Regimen
Workout Routine
Tom Selleck health and fitness regimen has evolved. adapting to his changing roles and age. During his "Magnum, P.I." days. Selleck's workouts were intense and focused on building and maintaining muscle mass. His routine included weightlifting, cardiovascular exercises. and specific training for the stunts he performed on the show.
Selleck adjusted his fitness routine as he aged to suit his body's needs. Today, his workouts focus on maintaining flexibility, strength, and cardiovascular health. He incorporates low-impact exercises such as swimming, walking, and light weightlifting. This balanced approach helps him stay fit without putting undue strain on his joints and muscles.
Importance of Flexibility and Mobility
In recent years, Selleck has emphasized the importance of flexibility and mobility in his fitness regimen. Understanding the natural decline in muscle mass and joint flexibility with age. he includes stretching and yoga in his routine. These practices help prevent injuries, improve posture, and maintain mobilit
Lung Cancer: Artificial Intelligence, Synergetics, Complex System Analysis, S...Oleg Kshivets
RESULTS: Overall life span (LS) was 2252.1±1742.5 days and cumulative 5-year survival (5YS) reached 73.2%, 10 years – 64.8%, 20 years – 42.5%. 513 LCP lived more than 5 years (LS=3124.6±1525.6 days), 148 LCP – more than 10 years (LS=5054.4±1504.1 days).199 LCP died because of LC (LS=562.7±374.5 days). 5YS of LCP after bi/lobectomies was significantly superior in comparison with LCP after pneumonectomies (78.1% vs.63.7%, P=0.00001 by log-rank test). AT significantly improved 5YS (66.3% vs. 34.8%) (P=0.00000 by log-rank test) only for LCP with N1-2. Cox modeling displayed that 5YS of LCP significantly depended on: phase transition (PT) early-invasive LC in terms of synergetics, PT N0—N12, cell ratio factors (ratio between cancer cells- CC and blood cells subpopulations), G1-3, histology, glucose, AT, blood cell circuit, prothrombin index, heparin tolerance, recalcification time (P=0.000-0.038). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and PT early-invasive LC (rank=1), PT N0—N12 (rank=2), thrombocytes/CC (3), erythrocytes/CC (4), eosinophils/CC (5), healthy cells/CC (6), lymphocytes/CC (7), segmented neutrophils/CC (8), stick neutrophils/CC (9), monocytes/CC (10); leucocytes/CC (11). Correct prediction of 5YS was 100% by neural networks computing (area under ROC curve=1.0; error=0.0).
CONCLUSIONS: 5YS of LCP after radical procedures significantly depended on: 1) PT early-invasive cancer; 2) PT N0--N12; 3) cell ratio factors; 4) blood cell circuit; 5) biochemical factors; 6) hemostasis system; 7) AT; 8) LC characteristics; 9) LC cell dynamics; 10) surgery type: lobectomy/pneumonectomy; 11) anthropometric data. Optimal diagnosis and treatment strategies for LC are: 1) screening and early detection of LC; 2) availability of experienced thoracic surgeons because of complexity of radical procedures; 3) aggressive en block surgery and adequate lymph node dissection for completeness; 4) precise prediction; 5) adjuvant chemoimmunoradiotherapy for LCP with unfavorable prognosis.
3. ESLD or Advanced HCC – LTx is the only cure
HCC – 2nd MCC in men & 6th MCC in women for cancer related mortality [1]
HCC is the only solid organ tumor to be treated with liver transplant.
5 year survival rate after LT for HCC – 60-70% [2]
No.of HCC patients waiting for LT >>> Available organ donors
Once in waitlist, the goals –
To keep waiting time short
To avoid drop-outs
To avoid tumor progression
4. Concept of Bridging Therapy
Reducing the amount of viable tumor in liver improves post-LT survival
No guidelines for the decision which patients should receive bridging therapy.
AASLD – Bridging therapy to every patient who is expected to wait for more than 6 months for LT. [3]
Best treatment option in Bridging therapy – remains unknown [4]
6. Curative treatment options for HCC
Ablation
Resection
LT
Resection
HCC with background normal liver parenchyma
5% of Western & 40% Asian patients [5]
Up to 70% can be resected
5 year survival 60-65% [6]
7. LT
HCC with an underlying cirrhosis
Goals
Complete removal of tumor & Undetected lesions
Removal of cirrhotic liver
Avoids risk of developing de-novo tumors in diseased cirrhotic liver
Multiple criterias
9. Currently no agreement on the selection of patients with advanced HCC for LT.
Milan criterias – too strict excluding patients expected to have good outcomes after LT
11. % HCC patients will be removed from LT list due to tumor progression – 20-30% [8]
Bridging therapy recommended for waiting time > 6 months for LT [9]
Risk factors for drop outs from waiting list [10]
1 tumor 3-5 cm
2 or 3 tumors
Lack of a complete response after 1st locoregional therapy
High AFP after 1st locoregional therapy
No randomized trials affecting the decision of type of bridging therapy
Choice depends on center’s experience
17. Can be used theoretically as 1st line bridging procedure
Theoretical advantages :
Best possible control of tumor growth TACE & Percutaneous treatments do not always achieve complete tumor
necrosis
Pathological analysis of specimen & selecting patients with poor prognostic factors for immediate LT evaluation
Dis-advantages
Higher costs
Peri-procedural risks
Ensuing LT technically more difficult with higher post-operative complications
18. Suitable patients
Well preserved liver function / No cirrhosis
Single exophytic / Subcapsular location tumors
Left lobe tumors
Salvage LT
HCC within MC with preserved LFT Can undergo Liver Resection
If tumor recurrence / Liver function failure Rescue LT
Effective in both settings DDLT & LDLT
Combination of prior recipient hepatectomy + a living donor graft provides excellent long term survival [11]
Belghiti et al – Primary LT in cirrhotic V/S Secondary LT after initial LR [12]
SIMILAR post-operative course, complications & 3 years & 5 years survival
19. Unsuitable for salvage LT
HCC recurrence overcoming conventional LT criteria
Age >65 years at time of recurrence
Severe comorbidities precluding LT
21. Most commonly used modality for waitlist patients with low major complication rate.
First line Treatment for BCLC intermediate stage HCC- BCLC stage B [13]
Partial response – 15-55% Improvement in median survival - 16-20 months [14]
2 types
Conventional TACE
DEB-TACE
22. Conventional TACE
Steps
1. Arterial infusion of lipiodol emulsion with chemotherapeutic agent [Doxorubicin/Cisplatin]
2. Embolization with gelfoam
Disadvantages
Require repetition either at regular intervals / at demands
Damage to non-cancerous hepatocytes function
Super selective TACE
Recommended for WaitList patients
To minimize ischemic injury to non-tumoural liver tissue
23. Conventional TACE
Limitation [15]
Not a standardized procedure
Optimal chemotherapeutic/embolization agent not yet determined
Re-treatment strategy not yet determined
24. DEB TACE
Drug Eluding Beads [DEB]- particles of various size
Able to bind & elute chemotherapeutic agent in a predictable manner [16]
Advantages [17]
More standardized approach
Less liver related toxicity
Less systemic adverse effects
25. Tumor necrosis s/p TACE
27-57% of complete tumor necrosis within MC [Milan Criteria] [18]
Rate of necrosis higher [19]
In Single nodule >> multiple nodules
Super selective TACE >> Conventional/Lobar TACE [ 53.8% v/s 29.8% ]
Nodules 3-5 cm >> Nodules < 3 cm
Larger nodules are fed by larger arteries – Chemoembolization more effective [18]
Small nodules lack fully developed arterial neo-angiogenesis
26. Kwan et al [18]
Pre-TACE angiogram
Avid lesion enhancement
Feeding vessel largen than 0.9mm diameter
Post-TACE angiogram
Lack of residual contrast enhancement
Decrease in lesion size
High density lesion due to an accumulation
Diffuse distribution of ethiodized oil throughout the lesion
Nicolini et al. - DEB-TACE v/s Conventional TACE [20]
77% v/s 27.2% tumor necrosis
>90% necrosis seen on explanted liver
Near complete lesion Necrosis
28. Small HCC not amenable to surgical resection.
Small & early HCC with a diameter of <3 cm [21]
Method
Cool tip / hook needles
Electrode placed percutaneously into targeted tissue
Alternate current Ionic frictions High temperatures
Rate of complete necrosis Size HCC [22]
Upto 3 cm 50-78%
> 3 cm 13-43%
Tumor > 3 cm Independent risk factor for persistence of HCC after RFA treatment
29. RFA related complications [23]
Just 3-4%
Acute cholecystitis
Arterial Haemorrhage
Biliary stenosis
Small bowel perforation
Tumor seeding at needle tract
Major limitations [24]
Proximity of tumor to biliary tree, gallbladder, caudate lobe & liver surface
Proximity to major vessels Heat sink effect
31. PEI
Oldest treatment for localized HCC
RARELY used as bridging
One multinational survey - Rate of complete necrosis < 30% for tumors < 3 cm [25]
PLA
Multiple tiny laser fibres
Tumor necrosis comparable to RFA
Rate of necrosis in nodules upto 3 cm – 62%
Advantages due to fine needles
High risk sites [ near vital structures ]
Severe clotting impairement
Where RFA is C/I
32. MWA
C/w RFA
Larger area of necrosis
Nodules in proximity to larger vessels can be treated [ No heat sink effect ]
Promising role
As a bridging procedure to LT
As downstaging procedure in HCC patients
33. TARE
With 90Yttrium microspheres
Riaz et al [26] – 38 HCC nodules in 35 patients
T2 HCC – 15 patients None progressed to T3 HCC before LT
Stage T3 – 10 patients [Downstaged] Stage T2 – 8 patients
Explant analysis – 61% complete tumor necrosis
Necrosis depends on size of lesion
< 3cm 89%
3 – 5 cm 65%
> 5cm 33%
34. CRT
Sandroussi C et al [27] – 5/6 fractions of RT to 10 patients of HCC on waitlist
Well tolerated
2 tumors remained stable
8 tumors showed 10-50% regression
LT in 5 patients
Explant pathology – 40-90% tumor necrosis
No recurrence at 6 months follow up
Further studies needed
36. Multi kinase inhibitor acting as anti-angiogenic drug
Vitale et al. [31] – Neoadjuvant sorafenib during WL v/s No bridging therapy
Beneficial effect on survival
Positive impact on transplant probability
Extend time to progression
Cost effective
BUT..
Evidence too small
Need RCT for justification to use as bridging therapy
Currently – Not recommended as standard therapy
38. Rationale
To reach a higher local tumor control rate by higher rate of complete tumor necrosis
RFA TACE or TACE RFA ?????
RFA Hyperemic rim surrounding ablation area Consequently targeted by TACE more effectively
TACE Reduced heat sink effect Larger ablation zones can be achieved with RFA
Ashoori et al [28] – 44 HCC patients within MC – TACE RFA
76.9% rate of complete tumor necrosis in 16 patients with 26 nodules who underwent LT
No major complications
39. CRT
Sandroussi C et al [27] – 5/6 fractions of RT to 10 patients of HCC on waitlist
Well tolerated
2 tumors remained stable
8 tumors showed 10-50% regression
LT in 5 patients
Explant pathology – 40-90% tumor necrosis
No recurrence at 6 months follow up
Further studies needed
41. Not recommended for waiting time < 6 months
Decision of bridging therapy depends on…
General health condition of patients
Limitations & C/I for each method
42. CONTRA-INDICATIONS
RFA
Tumors within 1 cm of main biliary
tract
IHBRD
Bilio-enteric anastomosis
Exophytic location of tumor
Untreated coagulopathy
TACE
Decompensated cirrhosis [CTP B8 &
higher]
Severely reduced portal vein flow
Renal insufficiency
Tumor size > 10cm
Untreated varices at high risk of
bleeding
Bile duct occlusion
Severe co-morbidities
TARE
Lung shunting > 20%
Estimated radiation doses for lung
>30 Gy [single administration]
>50 Gy [multiple administration]
Uncorrectable flow to GIT
CRT
Lesions within 2 cm of bowel due
to GI toxicity
50. T1 HCC – No evidence of benefits of bridging therapy [32]
T2 HCC
Waiting time < 6 months – no need of bridging therapy [32]
Waiting time > 6 months – bridging therapy is strongly recommended [AASLD, EASLD] [32, 33, 34]
Delay > 6-12 months without bridging therapy - Risk factor for… [8]
Tumour progression
Drop-out from waitlist
Interval dissemination causing post LT recurrence
Salvage LT
In prior hepatectomy with tumor recurrence within transplant criteria
In liver functional failure
Similar results with DDLT & LDLT
51. No recommendation for one type of locoregional therapy over others [32]
< 3 cm RFA
> 3cm TACE [ Selective/ Superselective >>> Conventional TACE ] [ DEB-TACE >>> Lipiodol TACE ]
Smaller lesion at sites dangerous for RFA PEI
Multimodal treatment strategies [ Sequential TACE & RFA ]
Response to neoadjuvant treatment assessment by mRECIST criteria by assessing…
Amount of necrosis &
Amount of residual tumour load
52. Advantages of bridging therapy in T2 HCC
Reduced drop out rate from waiting list
Positive impact on post-LT HCC recurrence
Positive impact on overall survival
Response in Pre-LT Surrogate marker of tumour biology
Helpful in Selection & Prioritization of candidates for LT
54. [1] Ferlay J, Parkin DM, Steliarova-Foucher E (2010) Estimates of cancer incidence and mortality in Europe in 2008. Eur J Cancer 46(4):765–781
[2] Jemal A, Siegel R, Xu J, Ward E (2010) Cancer statistics, 2010. CA Cancer J Clin 60(5):277–300
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[4] Forner A, Llovet JM, Bruix J (2012) Hepatocellular carcinoma. Lancet 379(9822):1245–1255
[5] European Association For The Study Of The L, European Organisation For R, Treatment Of C (2012) EASL-EORTC clinical practice guidelines: management of
hepatocellular carcinoma. J Hepatol 56(4):908–943
[6] Young AL, Adair R, Prasad KR, Toogood GJ, Lodge JP (2012) Hepatocellular carcinoma within a noncirrhotic, nonfibrotic, sero- negative liver: surgical approaches
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