Journal Club 29/01/2018 Paola Ponzo - PowerPoint Presentation

Slide1

Journal Club 29/01/2018Paola Ponzo

Slide2

Background:

CRC

:

fourth most common cancer worldwide

Slide3

Background:Malignancy

is

one of the leading cause of death in SOT recipients

CRC: from

no

association to 12-fold increase in SOT populationUS records: SIR 1.12 (CI 1.03-1.20)OLT  highest SIR 2.34 (CI 1.76-3.07)

Slide4

General population: median age at

diagnosis

72 y

Younger age in SOT

recipients

(

mean age 58 y)OLT: mean age 53 y

Earlier

develop

in SOT recipientsBIAS: older individuals not candidate for transplant

More aggressive

course: 5 years overall survival 30.7% (vs 63.5%)

Background :

Slide5

Risk

factors

:

General

population

Slide6

mTOR

inhibitors

 antineoplastic

properties

(inhibition of PI3K/AKT pathway), no clinical data about

their

protective

role in CRC MMF  inhibits adhesion of

CRC cells to intestinal epithelial cells

Risk factors – Role

of

Immunosuppression

:

CONS

:

Increasing

of

local

Treg



inhibition

of

effector T cell proliferation  inhibition of local immune systemCNI increasing of TGFβ production  inhibition of effector T cells CNI  angiogenesis stimulation through VEGFAzathioprine: directly damage of DNA

PR

OS:

Slide7

10-fold higher risk of CRC in PSC (mainly proximal to the splenic flexure)

R

isk factors for CRC and cirrhosis:

Risk

factors

– OLT: high alcohol intake, obesity

Slide8

Screening recommendations/ Pre

-

transplant

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Screening test : FULL COLONOSCOPY (post-transplant



increased risk of

proximal

CRC)

Screening recommendations/ Post - transplant

Slide10

Transplantation in patients with a

history

of colon

cancer

Data mainly derives from follow up in kidney transplantation

Only

small retrospective, single-center studies in liver transplant recipients  recurrence rate of ~ 19%5 years of negative follow up prior to listing for transplantation

Well-differentiated

Dukes’ A

(limited to the

muscularis propria) likely do not need a 5-year waiting period prior to listing.

Slide11

Active cancer: Stage 0 (

in situ)

ONLY IF

survival without transplant is “short” Above stage 0  NOT RECOMMENDED

Donors

with colon

cancerHistory of CRC: Donors with lower-risk lesions and a 5–10 years follow up can be considered

Suggestion

of using donors with a history of lower-risk lesions (in situ, T1, or T2); if they are 0, 1, and 5 years posttreatment respectively

Overall

transmission rate  19%

Slide12

mTOR inhibitors can prevent polyp formation in mice

mTOR

inhibitors reduce

the risk of de novo solid malignancies in kidney transplantation (RR 0.44; IC 0.24–0.82)potential benefit of mTOR inhibitor in reducing CRC risk (not statistically significant)

mTOR

inhibitors:Post – transplant colon cancer

Prevention

mTOR

inhibitors

should be considered if the risk of cancer is high

Slide13

Prophilactic colectomy (patients with PSC and UC):

Colectomy

before or during the

transplant  10 - year survival of 87% vs 60% (not statistically significant)



decreased

CRC- and UC-related morbidity Further studies are needed prior to recommend colectomy as standard of care in high risk patientsManagement

Lowering

doses

of the immunosuppressive regimen Potential beneficial effects of mTOR inhibitors and MMF inhibitors and tumorpromoting mechanisms of CNI  change immunosuppressive agent

Post – transplant colon

cancerPrevention

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Cancer and liver transplantation

Pre

–

transplant

screening

Mammogram

every 12-24 months (female > 40y, before in high risk patients)PAP smear every 3 years (female, 25-64 y)

Transvaginal

ECT and Ca-125

every

12 months (female)PSA and digital rectal examination (male; >50 y? frequency?) EGDSCRC: FOBT every 12 months or sigmoidoscopy every 5 y or

colonoscopy every 10 y (> 50 y or high risk patients)Dermatological examination

2008

Colonoscopy

(> 50 y)

EGDS

Mammogram and PAP smear (female)

Dermatological examination

Alcohol and smoking addiction: search for pulmonary

neoplasia,

ear-

nosethroat

, stomatology

,

oesophageal

and

bladder

Screening

for

prostate disease according to the urologist indication (male)2016

Slide15

Colonoscopy (> 50y or high risk

patients

)

EGDSChest-X-Ray

Abdomen

CT

scan (chest CT scan if HCC)ENT visitMammogram and PAP smear (female) every 12 monthsαFP

PSA (male)

every

12 monthsCancer and liver transplantationPre

– transplant screening

5 y of negative follow up in history of cancerMelanoma and breast cancer 

exclusion

Mieloproliferative

disorders

 no

controindication

What

do

we

do?

Slide16

Donors with previous or

current

malignancies

Livers

from a

donor with a history of malignancy can be used in selected situations (low risk of transmission)Low risk for low-grade CNS tumoursCRC and breast

cancer



absolute contraindications to

donation in advanced stage (CRC >T3 or breast cancer >T1c).Glioblastoma multiforme, melanoma, choriocarcinoma and lung cancer  absolute contraindications to liver donation

Cancer and liver transplantation

2016

Slide17

Donors with previous or

current

malignancies

Cancer

and

liver transplantationNON STANDARD CON RISCHIO TRASCURABILEK in situ (NO high grade breast cancer)Basocellular skin cancer G1-2

Spinocellular

skin

cancerPapillary urothelial carcinoma G1-2 intra-epithelial Papillary urothelial carcinoma G3 with negative f-uProstate cancer Gleason ≤ 6Papillary thyroid carcinomaRenal carcinoma (

low grade, < 4)Low grade CNS cancer (WHO G1-2-3)MGUS – MC > 1.5 g /dl

NON STANDARD CON RISCHIO ACCETTABILEHigh grade CNS cancer (WHO G4) with the exception of glioblastoma, gliosarcoma and embryonal tumours; without clinical high

risk

factors

Prostate

cancer

Gleason

>

6

2015

Slide18

Donors with previous or

current

malignancies

Cancer

and

liver transplantationNON IDONEO - RISCHIO INACCETTABILEFollow-up < 10 y (high risk tumors) Metastatic cancerBreast cancer

, Melanoma,

Limphoma

and Leukemia

High grade CNS cancer (WHO G4) with clinical high risk factors Glioblastoma, gliosarcoma, embryonal CNS tumours

2015

Slide19

Post-transplant follow up

2–3

-

fold elevated risk of

solid

organ cancers

and a 30-fold or higher increase in the rate of lymphoproliferative malignancies compared to the general population3-22 % of transplanted patientsMost common de novo malignancy: non-melanoma skin cancer (20x, spinocellular > basocellular)Cancer and liver

transplantation

Alcoholic cirrhosis: increased risk of cancer of the upper GI, oropharynx and larynx

Smoking history: increased risk of head/neck and pulmonary de novo malignancies EBV + before LT: higher risk of developing PTLD (aggressive, extra-nodal)PSC + UC: higher risk of CRC

Slide20

No screening programs based on scientific evidence

No

codified

/standardized screening programs

Proposed

screening:

Mammogram every 12-24 months (female,> 40y)PAP smear every 3 years (female)ECT TV+ Ca 125 every 12 monthsPSA and urological examination every 12

months

(male, > 50y)

CRC: FOBT every 12

months or sigmoidoscopy every 5 y or colonoscopy every 10 y (> 50 y or high risk patients)Dermatological evaluation every 12 monthsChest-X-Ray

every 12-24 months high risk patient: smokers,)EGDS and

ENT evaluation every 12 months (high risk patients: history of alcohol abuse, Barrett’s esophagus)

Post-

transplant

follow

up

Cancer

and

liver

transplantation

2008

2016

Slide21

Colonscopy every 5-10 years (more frequent

in high

risk

patients)Chest-X-Ray every 12

months

Mammogram

every 12 months (female)PAP smear every 12 months (female)ECT abdomen: 3-6-12 months and then

yearly

.

In HCC: abdomen CT

scan yearlyNo standardized indications for: EGDS, ENT evaluation, dermatological evaluation, PSA/urological evaluation

Post-

transplant follow upCancer

and

liver

transplantation

What

do

we

do

?

Slide22

What should we do? (Literature Review)

HCC

No

clear indications

. CT/MRI

every

6 months for 5 years?Liu D et al. Evidence Based surveillance Imaging Schedule After Liver Transplantation for Hepatocellular Carcinoma Recurrence. Transplantation; 2017Lung No clear indications

.

 

20% mortality reduction in heavy smokers (> 30 pack-years)

aged 55 -74 in screening with yearly low-dose chest CT scanLung cancer screening with low-radiation dose computed tomography after liver transplantation. Herrero JI et al. Ann Transplant; 2013 Post-transplant

follow up

Cancer and liver transplantationUpper GI

tract

No

clear

indications

. EGDS

every

2-3

years

< 40 y,

then

every

2

years

Jung DH. Survival Benefit of Early Cancer Detection Through Regular Endoscopic Screening for De Novo Gastric and Colorectal Cancers in Korean Liver Transplant Recipients. Transplant Proc. 2016

Slide23

Prostate/Breast No higher

risk

then general population (no screening/ ‘prevensione serena’)

Mukthinuthalapati

PK. Incidence, risk factors and outcomes of 

de novo malignancies post liver transplantation.World J Hepatol 2016Skin Dermatological evaluation every 12-24 months (6-12 months if: older

age

, phototype I-II-III, HPV +,

CD4+ deficiency, actinic keratosis, higher levels of immunosuppression)Krynitz B et al. Risk of skin cancer and other malignancies in kidney, liver, heart and lung transplant recipients 1970 to 2008 – a Swedish population-based study. Int J Cancer 2013Stasko

T et al. Guidelines for the management of squamous cell carcinoma in organ transplant recipients. Dermatol Surg 2004

What should we do? (Literature Review)Post-

transplant

follow

up

Cancer

and

liver

transplantation

Cervix

PAP

smear

every

12

months

if HPV +, no clear indications in other patients (‘prevenzione serena’?)Mukthinuthalapati PK. Incidence, risk factors and outcomes of de novo malignancies post liver transplantation.World J Hepatol 2016