Metastatic hepatocellular carcinoma case post liver transplantation

Nabil El-hady December 2014 1

Epidemiology

Hepatocellular carcinoma is the 5th most common malignancy worldwide & the 3rd cause of cancer related death with

male-to-female ratio

- :5 1 in Asia

- :2 1 in the United States

Tumor incidence varies significantly, depending on geographical location.HCC incidence increase with age.

- 53 years in Asia

- 67 years in the United States.Ref: Jemal, A., Bray, F., Center, M. M., Ferlay, J., Ward, E. and Forman, D. (2011), Global cancer

statistics. CA: A Cancer Journal for Clinicians, 61: 69–90. doi: 10.3322/caac.20107

Nabil El-hady December 2014

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Epidemiology


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Ref: Jemal, A., Bray, F., Center, M. M., Ferlay, J., Ward, E. and Forman, D. (2011), Global cancer statistics. CA: A Cancer Journal for Clinicians, 61: 69–90. doi: 10.3322/caac.20107

Etiology

1-Hepatitis B

- increase risk 100 -200 fold

- 90% of HCC are positive for (HBs Ag( 2-Hepatitis C

3-Cirrhosis

- 70% of HCC arise on top of cirrhosis

4-Toxins -Alcohol -Tobacco - Aflatoxins

5-Autoimmune hepatitis

6-States of insulin resistance- Overweight in males Diabetes mellitus


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Diagnosis

1-AFP produced by 70% of HCC

<400ng/ml

AFP increasing over time

2- Imaging

- focal lesion in the liver of a patient with cirrhosis is highly likely HCC

- Spiral CT of the liver

- MRI with contrast enhancement

3( Biopsy is rarely required for diagnosis


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Treatment

Surgical resection-1

2-Liver transplantation

3- Trans-arterial Chemo-embolization or Radio-embolization (Yttrium-90 microspheres(

or percutaneous ablation using alcohol

4-Radiofrequency ablation is a technique that makes use of a “heating” probe to destroy tumors within the liver.

5- target therapy e.g. : Sorafenib


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Treatment

Transplantation for HCC: Milan Criteria

1 lesion ≤5 cm

3 lesions ≤3 cm

No vascular invasion

No extra hepatic metastases

Dec. 9, 2008 on-line liver cancer video program for medical professionals by Paul Kwo, MD and American Liver Foundation


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Treatment


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Patient case


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Patient case

CC :Community-acquired pneumonia !?HPI :

Mr. H.A 73 years old gentleman presented with history of fever& productive cough for the past 3 days, no chest pain ,no SOB.On examination: Afebrile, vitally stable.

Chest x-ray @ 27/11 : -multiple pulmonary nodules with right side infiltrates

-haziness of right lower lung zone probably pneumonic

Procalcitoin : 0.86 @27/11 27/11 @C-reactive protein : 111


Patient case

PMH

Mr. HA 73 years old gentleman is a known case of hepato-cellular carcinoma ,with HCV&HBV Past infection ,DM &HTN

-On November 2008 pt receive 2 session of alcohol injection &1 session of chemobolization and he was stable after that .

-On october 2009 the alpha feto protein was high ,pt was started on sorafinib 400 mg po. Bid then decreased to 200 mg po. Bid due to HFS ,then resumed again as the alpha feto-protein was keep rising

- Did liver transplantation at china @ 2010

- Receive radiotherapy twice in 2012


Patient case

PMH

- Recently on June 2013 disease progressed and metastasized to lung ,bone & adrenal gland

- Patient then received 1 cycle of doxorubicin iv 60 mg /m2 on 11/2013 + sorafinib 400 mg p.o BID ( badly tolerated : Mucositis and neutropenia(

-since January 2014 patient was followed up regularly & as per decision of multidisciplinary team to consider best supportive care, But the patient ask for further management, so they decide to rechallenge with sorafenib after 6 month break

Note :family said patient had isotopes implant for the adrenal mets at china ( require to wear lead jacket (


Patient case


Demographics

Review of system : Admission date : 27/11/2014

Height : 156 weight : 46 FHX : Married SHX: Not remarkable

Allergy : NKDA

Admission : CNS ,HEENT EXTREMETIES … normal Chest ,CVS : Difficult to examine due to lead jacket

) for isotopes implants (


Patient case

Home medications:

Rabeprazole 20 mg once daily p.o

Morphine syrup 2.5 ml Q2H p.o prn for pain Amlodipine 5 mg once daily p.o. Metocloperamide 10 mg q6h po.

Tacrolimus 0.5 mg twice daily p.o. Tenofovir 245 mg once daily p.o.

Sorafinib 400 mg po. Bid


Lab value at admission date 27/11/2014

Weight 46 kg Chemistry Coagulation profile

Height 156 cm Na 130 mmol/L INR 1.2

Vitals K 4.9 mmol/L APTT 31.6 sec

Temp 37 ºC Cl 99 mmol/L PT 13.3 sec

HR 76 b/min HCO3 17 mmol/L LFT

BP 130/70 mm Hg Glucose 18 mmol/l ALT 19 U/L

RR 16 b/min Urea nitrogen 11.9 mmol/L AST 25 U/L

Hematology SCr 159 μmol/L Albumin 22 g/L

Platelet 315 x10³/μl CrCL 23.8ml/min LactateDehydrogenase

329 U/L

WBC 19.5 x10/μl³ Cor. Ca 1.9 mmol/L Bilirubin

4 μmol/L

ANC 18.2 URIC ACID 266 ummol/L procalcitonin 0.86

Alpha feto protein =02/11/2014 = 3825 ( 0-5 ) Tacrolimus level = 15/5/2014 = 7.1 ( 8.5 – 17 )

Lab values


Lab values


High WBCS counts and high ANC along with the result from chest x-ray showing multiple pulmonary nodules with right side infiltrates-haziness of right lower lung zone probably pneumonicConfirms Community acquired pneumonia

Lab values


Lab values


Mr. H.A sr.cr = 159 umol/l (1.5 to 2 time from baseline) he is at risk of acute kidney injury according to RIFLE Classification and require reassessment of his current medication therapy

Note : Base line sr.cr for in Mr. H.A case should be 88 umol/l ( nonblack man > 65 y.o)

Ref: Bellomo R, Ronco C, Kellum JA et al. Acute renal failure - definition, outcome measures, animal models, fluid therapy and information technology needs: theSecond International Consensus Conference of the Acute Dialysis Quality Initiative (ADQI) Group. Crit Care 2004; 8: R204-212

Lab values


Identified drug related problems

4 major Drug related problems

1-Mr. H.A experience CAP which require additional drug therapy

2-Mr. H.A sr.cr = 159 umol/l (1.5 to 2 time from baseline) he is at risk of acute kidney injury according to RIFLE Classification and require reassessment of his current medication therapy ( renal dose adjustment & remove all offending

causes )

3- Mr. H.A HCC metastasized to bone and he is on long term use of tenofovir

( decrease bone mineral density ) and he require additional drug treatment for this condition

4-Mr.H.A experience hand foot syndrome ( grade 3 ) a side effect from sorfininb and require reassessment of his current therapy


Community Acquired Pneumonia -1

Desired clinical outcome

Eradicate infection within 5 to 10 days ,continue ttt until patient should be afebrile for 48-72 hours, stable blood pressure, adequate oral intake, and room air oxygen saturation of greaterthan 90%

Therapeutic alternatives

1-respiratory fluroquinolone Levofloxacin 750 mg IV or PO q24h or Moxifloxacin 400 mg IV or PO q24h

2-Combination of a beta-lactam (ceftriaxone 2 g IV q24h or cefotaxime 1 g IV q8h or ertapenem 1 g IV daily or ceftaroline 600 mg IV q12h) plus azithromycin 500 mg IV q24h

Recommendation Ceftriaxone 2 gm iv once daily + azithromycin 500 mg iv once daily

Justification 1-based on CURB-65 score the patient score is 2 ( age >65 & Presence of confusion) So the patient should be treated as inpatient –non icu

2-the Creatinine clearance on admission is deteriorated 23.8 @28/11/2014 and this will require dose adjustment for both levofloxacin and moxifloxacin while no need for dose adjustment of ceftriaxone and azithromycin


Community Acquired Pneumonia -1


Initial chest x-ray upon admission

chest x-ray after 3 days from starting medication

2-acute kidney injury Desired clinical outcome :

prevent complication such as Chronic kidney injury ,Fluid overload& Hyperkalemia

Plan :1-Treat the underlying causes

A-change the dose of metocloperamide from 10 mg q6h to 5 mg iv prn ( to decrease the load on kidney (

B-the dose heparin for DVT prophylaxis should be 5000 units sc bid )renal dose(

C-change the frequency of tenofovir as 245 mg po q72 hr As cr.cl upon admission = 23.8 ml/min And consider increase frequency to q48hr if

30 <cr.cl>49 ml/min And to be once daily if cr.cl >=50 ml/min .


2-acute kidney injury

2-Discontinue offending agents (Rabeprazole(There is a growing body of literature suggests that proton pump inhibitors may be linked to acute kidney injury, which can potentially lead to chronic injury or kidney failure

so I recommend to change PPI ranitidine 50 mg once ( renal dose (Beside the patient is receiving medication known to worsen the

kidney function ( tenofovir (

Ref: Ref: Sierra F, Suarez M, Rey M, Vela MF: Systematic review: proton pumps inhibitor-associated acute interstitial nephritis. Aliment PharmacolTher2007, 26:545–553.


3-bone metastasis

Desired clinical outcome prevent skeletal related events (like fractures ) & hypercalcemia

Therapeutic alternatives 1-calcium & vit d supplementation 2-Bisphosphonate 3-RANKL inhbitors

Recommendation RANKL inhibitor ( Denosumab 60 mg sc Q6 months )

Justification 1-pt already had bone mets putting him at further risk2-long term use of tenofovir is associated with decreased bone

mineral density3-The renal function of patient is deteriorated ( 23.8 ml/min upon

admission )so zoledronic acid is not the best option for this patient

4-discontinuation of tenofovir is not advised due to risk of HBV recurrence post liver transplant


4-Hand foot syndrome


Desired clinical outcome 1-resolve patient specific symptoms (moist desquamation, ulceration, blistering, or severe pain of the hands or feet or severe discomfort that prevents working or performing daily activities)

2- prevent delay of chemotherapy

Therapeutic alternatives 1-first or second occurrence: Hold treatment until resolves to grade 0-1 then resume treatment with dose reduced by one dose level

(400 mg daily or 400 mg every other day).2-Third occurrence: Discontinue treatment

Recommendation Discontinue of sorafininb and consult palliative team for best supportive care

Justification 1-the patient experience dermatologic toxicity on sorafininb grade 3 for the third time

2-the tumor marker is keep rising on sorafinib ( last alpha-feto protein is 02/11/2014 =3825 )

Metastatic hepatocellular carcinoma case post liver transplantation

Health & Medicine

Transcript of Metastatic hepatocellular carcinoma case post liver transplantation