Neoadjuvant chemoradiation (NACRT) aims to downstage disease and increase resection rates for locally advanced esophageal cancer. Several trials have shown mixed results. Some found NACRT improved survival rates and resection margins compared to surgery alone, while others found no survival benefit or increased postoperative mortality with NACRT. Recent meta-analyses found NACRT increased histopathological responses and R1 resection rates but not overall survival. The optimal neoadjuvant treatment regimen remains controversial, and further studies are still needed.
Induction chemotherapy followed by concurrent ct rt versus ct-rt in advanced ...Santam Chakraborty
Small Presentation where the benefit of addition of induction / neoadjuvant chemotherapy to concurrent chemoradiation in head neck cancers is explored.
Results of Stereotactic Body Radiotherapy (SBRT) for Management of Hepatic Tu...Premier Publishers
PURPOSE: To evaluate early outcomes of hepatic tumors treated with robotic SBRT (cyberknife).
MATERIALS AND METHODS: Between March 2007 and December 2012; 59 patients: 48 Hepatic Metastases (HM), 8 Hepatocellular Carcinoma (HCC), 3 Cholangiocarcinoma (CC).
CTV margin for HCC and CC was 5 mm, PTV margin: 3 mm. no margin for HM.
Median dose: 47.61 Gy in 3 fractions prescribed to 80 % isodose line.
RESULTS: we report 1 grade 3 toxicity.
HCC; overall survival (OS): 41.7% at 1 year, local control (LC): 75% at 1 year.
At 1 and 2 years we report, respectively.
HM; OS: 83.6% and 57%, disease free survival (DFS): 69.5% and 46.1%, LC: 76.3% and 57.9%.
CC; OS: 100% and 50%, DFS and LC: 50% and 0%.
Factors influencing better OS; type of lesion, age < 65 years (p= 0.033), small PTV volume
(p= 0.002), for DFS; dose of 45 Gy (p= 0.001), dose per fraction of 15 Gy (p= 0.001), coverage > 95% for PTV (p= 0.001), For LC; type of lesion, dose to PTV (p= 0.037), coverage > 95% for PTV (p= 0.001).
CONCLUSION: Age, volume of tumor, dose, coverage of target volume are prognostic factors for survival and LC.
Esophagus has rich submucosal network of lymphatics which makes longitudinal spread of tumor prevalent.There is propensity for early spread and widespread nodal metastasis.
Adequate proximal (10 cm) and distal resection margin must be achieved.
Early management of SBS includes replacement of fluid and electrolytes.
Enteral feeding should begin once the patient stabilizes.
Continuous enteral feeding is preferred.
For enteral feedings, hypoallergenic protein hydrolysate formulas or breast milk are usually best tolerated
Reconstruction of complex defects of the anterior abdomen is both challenging and technically demanding for reconstructive surgeons. Omentum- mesh –skin technique is the solution for closure of such large defects
According to a Lancet study (2012), in India, tobacco-related cancers represented 42·0% of male and 18·3% of female cancer deaths
India also has one of the highest rates of oral cancer in the world as the consequence of high prevalence of smokeless tobacco use
Pulmonary Thromboembolism - etilogy, types, medical- Surgical and nursing man...VarunMahajani
Disruption of blood supply to lung alveoli due to blockage of one or more pulmonary blood vessels is called as Pulmonary thromboembolism. In this presentation we will discuss its causes, types and its management in depth.
Anti ulcer drugs and their Advance pharmacology ||
Anti-ulcer drugs are medications used to prevent and treat ulcers in the stomach and upper part of the small intestine (duodenal ulcers). These ulcers are often caused by an imbalance between stomach acid and the mucosal lining, which protects the stomach lining.
||Scope: Overview of various classes of anti-ulcer drugs, their mechanisms of action, indications, side effects, and clinical considerations.
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
Title: Sense of Smell
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the primary categories of smells and the concept of odor blindness.
Explain the structure and location of the olfactory membrane and mucosa, including the types and roles of cells involved in olfaction.
Describe the pathway and mechanisms of olfactory signal transmission from the olfactory receptors to the brain.
Illustrate the biochemical cascade triggered by odorant binding to olfactory receptors, including the role of G-proteins and second messengers in generating an action potential.
Identify different types of olfactory disorders such as anosmia, hyposmia, hyperosmia, and dysosmia, including their potential causes.
Key Topics:
Olfactory Genes:
3% of the human genome accounts for olfactory genes.
400 genes for odorant receptors.
Olfactory Membrane:
Located in the superior part of the nasal cavity.
Medially: Folds downward along the superior septum.
Laterally: Folds over the superior turbinate and upper surface of the middle turbinate.
Total surface area: 5-10 square centimeters.
Olfactory Mucosa:
Olfactory Cells: Bipolar nerve cells derived from the CNS (100 million), with 4-25 olfactory cilia per cell.
Sustentacular Cells: Produce mucus and maintain ionic and molecular environment.
Basal Cells: Replace worn-out olfactory cells with an average lifespan of 1-2 months.
Bowman’s Gland: Secretes mucus.
Stimulation of Olfactory Cells:
Odorant dissolves in mucus and attaches to receptors on olfactory cilia.
Involves a cascade effect through G-proteins and second messengers, leading to depolarization and action potential generation in the olfactory nerve.
Quality of a Good Odorant:
Small (3-20 Carbon atoms), volatile, water-soluble, and lipid-soluble.
Facilitated by odorant-binding proteins in mucus.
Membrane Potential and Action Potential:
Resting membrane potential: -55mV.
Action potential frequency in the olfactory nerve increases with odorant strength.
Adaptation Towards the Sense of Smell:
Rapid adaptation within the first second, with further slow adaptation.
Psychological adaptation greater than receptor adaptation, involving feedback inhibition from the central nervous system.
Primary Sensations of Smell:
Camphoraceous, Musky, Floral, Pepperminty, Ethereal, Pungent, Putrid.
Odor Detection Threshold:
Examples: Hydrogen sulfide (0.0005 ppm), Methyl-mercaptan (0.002 ppm).
Some toxic substances are odorless at lethal concentrations.
Characteristics of Smell:
Odor blindness for single substances due to lack of appropriate receptor protein.
Behavioral and emotional influences of smell.
Transmission of Olfactory Signals:
From olfactory cells to glomeruli in the olfactory bulb, involving lateral inhibition.
Primitive, less old, and new olfactory systems with different path
Report Back from SGO 2024: What’s the Latest in Cervical Cancer?bkling
Are you curious about what’s new in cervical cancer research or unsure what the findings mean? Join Dr. Emily Ko, a gynecologic oncologist at Penn Medicine, to learn about the latest updates from the Society of Gynecologic Oncology (SGO) 2024 Annual Meeting on Women’s Cancer. Dr. Ko will discuss what the research presented at the conference means for you and answer your questions about the new developments.
Ethanol (CH3CH2OH), or beverage alcohol, is a two-carbon alcohol
that is rapidly distributed in the body and brain. Ethanol alters many
neurochemical systems and has rewarding and addictive properties. It
is the oldest recreational drug and likely contributes to more morbidity,
mortality, and public health costs than all illicit drugs combined. The
5th edition of the Diagnostic and Statistical Manual of Mental Disorders
(DSM-5) integrates alcohol abuse and alcohol dependence into a single
disorder called alcohol use disorder (AUD), with mild, moderate,
and severe subclassifications (American Psychiatric Association, 2013).
In the DSM-5, all types of substance abuse and dependence have been
combined into a single substance use disorder (SUD) on a continuum
from mild to severe. A diagnosis of AUD requires that at least two of
the 11 DSM-5 behaviors be present within a 12-month period (mild
AUD: 2–3 criteria; moderate AUD: 4–5 criteria; severe AUD: 6–11 criteria).
The four main behavioral effects of AUD are impaired control over
drinking, negative social consequences, risky use, and altered physiological
effects (tolerance, withdrawal). This chapter presents an overview
of the prevalence and harmful consequences of AUD in the U.S.,
the systemic nature of the disease, neurocircuitry and stages of AUD,
comorbidities, fetal alcohol spectrum disorders, genetic risk factors, and
pharmacotherapies for AUD.
- Video recording of this lecture in English language: https://youtu.be/lK81BzxMqdo
- Video recording of this lecture in Arabic language: https://youtu.be/Ve4P0COk9OI
- Link to download the book free: https://nephrotube.blogspot.com/p/nephrotube-nephrology-books.html
- Link to NephroTube website: www.NephroTube.com
- Link to NephroTube social media accounts: https://nephrotube.blogspot.com/p/join-nephrotube-on-social-media.html
Explore natural remedies for syphilis treatment in Singapore. Discover alternative therapies, herbal remedies, and lifestyle changes that may complement conventional treatments. Learn about holistic approaches to managing syphilis symptoms and supporting overall health.
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.
Role of neoadjuvant chemoradiation in locally advanced carcinoma
1. Role Of Neoadjuvant Chemoradiation In Locally Advanced
Carcinoma Esophagus
DR NEELAM AHIRWAR
2. • The aim of combining neoadjuvant chemotherapy and radiotherapy is
to use the radiosensitising effects of chemotherapy to reduce the
tumour size and maximise local control
3. Neoadjuvant CRT
• Downstage the disease
• Increase the rate of complete resection with negative margins
• Eradicate occult micrometastasis
• Reduce risk of local recurrence
4.
5. Irish trial
• 58 patients were randomized to neoadjuvant chemoradiation with two cycles of 5-FU
and cisplatin with 40 Gy radiation in 15 fractions followed by surgery versus surgery
• statistically significant survival advantage in the neoadjuvant group (median survival of16
months) compared to the upfront surgery group (median survivalof 11 months
• criticized -small sample size, short median follow up (average 10 months
Walsh TN, Noonan N, Hollywood D, Kelly A, Keeling N, HennessyTP. A comparison of multimodal
therapy and surgery for esophageal adenocarcinoma. N Engl J Med. 1996;335(7):462–7.
6. EORTC trial
• Evaluated patients with squamous cell carcinoma and compared neoadjuvant CRT followed by
surgery with surgery alone.
• Radiation was delivered in two one-weekly courses, 2 weeks apart, with five daily fractions of 3.7 gy
each; cisplatin was given before each course of radiation
• Complete pathological response was seen in 26% of patients with combined treatment
• DRAWBACKS - higher mortality rate was attributed to the higher dose of radiation per fraction, the
use of cisplatin monotherapy
Bosset J-F, Gignoux M, Triboulet J-P, Tiret E, Mantion G, Elias D, et al. Chemoradiotherapy followed
by surgery compared with surgeryalone in squamous-cell cancer of the esophagus. N Engl J
Med.1997;337(3):161–7.
7. The Trans-Tasman Radiation Oncology Group (TROG) and the
Australasian Gastro-Intestinal Trials Group (AGITG)
• randomized 256 patients equally to surgery alone (128) or to neoadjuvant chemoradiation
followed by surgery (128)
• One cycle of cisplatin and 5-FU was given along with 35 Gy radiation (in 15 days) in the neoadjuvant
treatment group
• no benefit with NACRT in either PFS or OS, although a subset analysis showed superior survival in patients
with squamous cell carcinoma
• This trial was criticized for the suboptimaldose of radiation (35 Gy) and single cycle of chemotherapy
Burmeister BH, Smithers BM, Gebski V, Fitzgerald L, Simes RJ,Devitt P, et al. Surgery alone versus
chemoradiotherapy followed by surgery for resectable cancer of the oesophagus: a randomisedcontrolled
phase III trial. Lancet Oncol. 2005;6(9):659–68.
8.
9. CALGB 9781
• An intent-to-treat analysis showed a median survival of 4.48 v 1.79
years in favor of trimodality therapy (exact stratified log-rank, P .002)
• Five-year survival was 39% (95% CI, 21% to 57%) v 16% (95% CI, 5%
to 33%) in favor of trimodality therapy
10. CROSS trial
• The role of NACRT has now been widely accepted globally
• Patients in the neoadjuvant chemoradiation group received weekly carboplatin and paclitaxel
for 5 weeks with a radiation dose of 41.4 Gy in 23 fractions.
• Statistically significant R0 resections were seen in the neoadjuvant CRT group.
• Median overall survival was 49.4 months in the CRT followed by surgery group and 24 months
in the surgery group (P = .003)
• no significant difference in postoperative morbidity or mortality
van Hagen P, Hulshof M, van Lanschot J, Steyerberg EW,Henegouwen MIVB, Wijnhoven B, et al.
Preoperative chemoradiotherapy for esophageal or junctional cancer. N Engl J
Med.2012;366(22):2074–84
11. CROSS TRIAL
• Long-term results confirmed the overall survival advantage with
neoadjuvant CRT in all subgroups and also improved DFS, and local
and distant recurrence rates
Shapiro J, Van Lanschot JJ, Hulshof MC, van Hagen P, van Berge Henegouwen MI,
Wijnhoven BPL, et al. Neoadjuvant chemoradiotherapy plus surgery versus surgery
alone for oesophageal or junctionalcancer (CROSS): long-term results of a randomised
controlledtrial. Lancet Oncol. 2015;16(9):1090–8.
13. Strength- pretherapy staging (EUS,Laparoscopy)
Randomised 119 patients with siewart I-III
CRT –
• significant higher pathologic complete response (15.6% v 2.0%)
• higher tumor-free lymph nodes (64.4% v 37.7%) at resection
• 3-year survival rate from 27.7% to 47.4%
Postoperative mortality was non significantly increased in the chemoradiotherapy group
Stahl M, Walz MK, Stuschke M, Lehmann N, Meyer H-J, Riera-Knorrenschild J, et al. Phase III comparison of
preoperative chemotherapy compared with chemoradiotherapy in patients with locally advanced
adenocarcinoma of the esophagogastric junction. J ClinOncol. 2009;27(6):851–6.
14. POET TRIAL
• Local progression-free survival after tumour resection was significantly
improved by CRT (hazard ratio [HR] 0.37; p = value 0.01) and 20 versus
12 patients were free of local tumour progression at 5 years
Stahl M, Walz MK, Riera-Knorrenschild J, Stuschke M, SandermannA, Bitzer M, et al. Preoperative
chemotherapy versus chemoradiotherapyin locally advanced adenocarcinomas of the oesophagogastricjunction
(POET): long-term results of a controlled randomisedtrial. Eur J Cancer. 2017;81:183–90
15. • the study closed early,
• median OS and PFS showed a statistically insignificant trend favoring the NACRT arm,
but the postoperative in hospital mortality was 10.2% in the NACRT arm compared to
3.8% in the NACTarm.
16. • Patients assigned to arm A received 12 applications of chemotherapy with
weekly 5- fluorouracil (2000 mg/m2 , 24 h infusion)/folinic acid (500
mg/m2 , 2 h infusion) and biweekly cisplatin (50 mg/ m2 , 1 h infusion),
within 14 weeks, followed by another 3-weekly applications.
• Patients assigned to arm B received the same 14-weeks chemotherapy for
induction, followed by a 3-week course of combined CRT with cisplatin (50
mg/m2 , 1 h infusion, days 2 and 8) and etoposide (80 mg/m2 , 1 h
infusion, days 3-5)
• A total dose of 30 Gy was applied, using 15 fractions of 2 Gy within 3 weeks
17.
18. • Patients were randomised to receive preoperative CT with cisplatin
(80 mg/m2 ) and infusional 5 fluorouracil (1000 mg/m2 /d) on days 1
and 21, or preoperative CRT with the same drugs accompanied by
concurrent radiation therapy commencing on day 21 of
chemotherapy and the 5 fluorouracil reduced to 800 mg/m2 /d. The
radiation dose was 35 Gy in 15 fractions over 3 weeks.
19. • In the CT arm the median PFS and OS were 14 and 29 months and for CRT the median
PFS and OS were 26 and 32 months. The overall 5 year survival was 36% in the CT group
and 45% for those having CRT
• The overall loco-regional recurrence rate was 28% in the CT group compared with 18% in
the CRT group
• Following CRT, five patients (13%) had a pathological complete response but none were
seen after CT
• addition of concurrent radiation therapy at a dose of 35 Gy to preoperative CT did not
add to CT toxicity or surgical morbidity
• Small and underpowered
20. NeoRes trial
• complete responses (the primary endpoint) and R-0 resection rates were higher with NACRT,
overall survival was identical in the two groups
• An updated report with longer follow up confirmed the lack of benefit in overall survival and there
were no differences in recurrence patterns
24. • Toxicity was similar for CT and CRT.
• The histopathological response rate (CRT 31% versus CT 8%, p = 0.01)
• R1 resection rate (CRT 0% versus CT 11%, p = 0.04) favoured those receiving CRT.
• no difference in survival,
improvement from preoperative CRT with respect to margin involvement makes
NACRT a reasonable option for bulky, locally advanced resectable adenocarcinoma
of the oesophagus
25. • Showed weak evidence in favour of neoadjuvant chemoradiotherapy,
but this comparison might also have been prone to selection bias
• A clear advantage has not been established