2.2 Tóm-Tắt-Luận-Án (Anh).Docx

BỘ GIÁO DỤC VÀ ĐÀO TẠO BỘ QUỐC PHÒNG HỌC VIỆN QUÂN Y NGÔ VIẾT THI NGHIÊN CỨU CHẪN ĐOÁN VÀ ĐIỀU TRỊ PHẪU THUẬT UNG THƯ BIỂU MÔ TẾ BÀO GAN Ở NGƯỜI CAO TUỔI Chuyên ngành NGOẠI TIÊU HÓA Mã số 62 72 01 25[.]

BỘ GIÁO DỤC VÀ ĐÀO TẠO BỘ QUỐC PHÒNG

HỌC VIỆN QUÂN Y

NGÔ VIẾT THI

NGHIÊN CỨU CHẪN ĐOÁN VÀ ĐIỀU TRỊ PHẪU THUẬT UNG THƯ BIỂU MÔ TẾ BÀO GAN Ở NGƯỜI CAO TUỔI

Chuyên ngành: NGOẠI TIÊU HÓA

Mã số: 62 72 01 25

TÓM TẮT LUẬN ÁN TIẾN SỸ

HÀ NỘI - 2022

MILITARY MEDICAL UNIVERSITY

NGO VIET THI

RESEARCH ON DIAGNOSIS AND SURGICAL THERARPY OF HEPATOCELLULAR CARCINOMA IN ELDERLY PATIENTS

Major: Surgery Number code: 9720104

SUMMARY OF MEDICAL DOCTORAL THESIS

HA NOI - 2023

Supervisor:

1 Assoc., Prof Nguyen Van Xuyen

2 Assoc., Prof Le Thanh Son

Reviewer 1: Assoc., Prof Pham Đuc Huan

Reviewer 2: Assoc., Prof Vu Huy Nung

Reviewer 3: Assoc., Prof Trinh Tuan Dung

This thesis has been defended at Institute-level Thesis Evaluation Council at 14.00 ………

Thesis can be found at:

1 National Library

2 Library of Viet Nam Military Medical University

Aging is associated with increasing susceptibility to development

of multiple chronic diseases due to progressive degeneration of theorgans and tissues

The world's older population has grown at an unprecedented rate

in the past 30 years

The global population aged 60 years or over numbered

378 million in 1980 This number rose to 759 million older personsand is projected to reach 2 billion by 2050 Vietnam is notexceptional In Viet Nam, the aging index has increased quickly inthe past three decades: the aging index was 7.2% in 1989, 8.3% in

1999 and 9.5% in 2009

According recent reports, hepatocellular carcinoma (HCC) is themost common type of liver cancer and the fourth leading cause ofcancer-related deaths worldwide The highest incidence and mortality

of HCC are observed in Southest Asia including Vietnam and Saharan Africa; but rarely encountered in Americas, Europe, andNorth America It is the most frequent cancer among males withhigher incidence of deaths

Sub-Despite advancement in medicine, better knowlege of etilogy andpathogenesis as well as more effective prevention of HCC, it is

a malignant cancer characterized by rapid progression, poorprognosis and high rate of mortality While hepatectomy still remains

a mainstay of HCC treatment, other approaches include: hepaticartery ligation, ethanol injection, hepatic endoarterialchemoembolization, radiofrequency ablation, radiation therapy.However, hepatic resection remains the most effective treatment What are clinical and laboratory symptoms of HCC and whichapproach is effective for management HCC among the elderly? From

the issue, the author conducted “Research on diagnosis and surgical

therarpy of hepatocellular carcinoma in elderly patients” aiming:

1 To present clinical and subclinical features of HCC among the elderly undergoing hepatectomy using Takasaki's technique

2 To evaluate surgical outcome and related factores of hepactectomy using Takasaki's technique for managment of HCC among elderly patients

New contribution of the thesis:

This research has made some valuable contributions toward thespecialties of hepatology and medical science as a whole Theresearch has provided fundamental knowledge of HCC among theelderly both clinically and subclinically Moreover, surgical outcome

of hepatectomy with Takasaki's procedure for treating HCC andsome related factors to survival, recurrence of HCC have beenaddressed in the current study

Organization of the thesis

The thesis is comprised of 118 pages, of which there are 02pages for Introduction, 40 pages for Overview - Chapter 1, 24 pagesfor Subjects and Methods – Chapter 2, 24 pages for Results - Chapter

3, 27 pages for Discussion; 02 pages for Conclusion; 01 page forRecommendations; 01 page for Lists of published research related toresearch findings The thesis also includes 25 tables, 20 figures and

10 charts There is a total of 149 references numbering 20 ones inVietnamese and 129 in Enlgish

CHAPTER 1 OVERVIEW

1.1 Overview of the elderly

1.1.1 Definition

Ageing is a course of biological nature, which is beyond humancontrol It has a variety of meanings depending on characteristics ofeach society Therefore, its definitions vary among countries andregions In developed countries, older people are commonly defined

as those aged 65 years or more UN defines older persons as thoseaged 60 year or over This boundary is kept fixed for calculations.This definition is prescribed in the Vietnam Law on the Elderly

1.1.2 Demographic characteristics of the elderly in the world and in Vietnam

Population ageing is a global phenomenon, occurring in virtuallyevery country in the world Global population is experiencing growth

in the size and proportion of older persons

Countries across the globe are aging; however, the rate ofpopulation aging in developing countries is rising at a pace amongthe highest in the world On average, the world's older population isprojected to increase by 29 million people annually, over 80% ofwhich are in developing countries The proportion of older people in

developing countries was 65% in 2010 and continutes to grow by80% by 2050.

1.1.3 The elderly’s health condition

The older persons are often susceptible to development ofmultiple chronic diseases due to progressive degeneration of thetissues and organs Recent findings of health condition among theelderly revealed poor health in 18.1- 57.7% according to self-assessment; four fifths of the elderly develop chronic disease andeach older persons has on average 2.1 chronic illnesses

1.2 Diagnosis of Hepatocellular Carcinoma

Symptoms of HCC often don't appear until the later stages of thecancer This used to be main cause of delayed diagnosis of livercancer which was little treated radically Currently, with the advert ofmedical improvement providing better understanding of risk factors,screening programmes as well as the aid of more accurate diagnosticmodels, HCC is diagnosed more accurately at an early stage

1.1.4 Prognostic role of biomarkers for HCC.

1.1.4.1 Alpha – Feto Protein (AFP)

Alpha-fetoprotein (AFP) is a glycoprotein produced primarily bythe fetal liver In adults, increased AFP levels may suggest thepresence of HCC; nevertheless, there are other causes of increasedlevels such as chronic hepatitis, testicular cancer, bile duct cancer According to 2010 AASLD, for HCC tumors with adiameter under 5 cm, the sensitivity, specificity and positivepredictive value of AFP are as follows:

Table 1.1: Diagnostic value of AFP for HCC.

especially AFP threshold < 400 ng/mL, which can be of little value indiagnosis of HCC.

1.1.4.2 Performance of different tumor markers for management

of HCC

- Lens culinaris agglutinin-reactive fraction of AFP (AFP-L3):AFP-L3 is used to distinguish patients with HCC from those withnonmalignant chronic hepatitis B Its thredhold value is 5%

- Prothrombin induced by vitamin K absence-II (PIVKA II) orknown as Des-gamma-carboxyprothrombin (DCP): Serum PIVKA-II

is an abnormal prothrombin protein An elevated serum level ofPIVKA-II is reported to be associated with HCC Its thredhold value

is 40 mAU/ml

- Recently, novel serum biomarkers including Golgi protein

73 (GP73), glypican-3 (GPC-3), Osteopontin, circulating cell freeDNA, and microRNA have proved no remarkeable role of HCCdiagnosis as well as economic efficiency

- Combined determination of serum AFP, AFP-L3 and PIVKA-IIcould improve the sensitivity in HCC screening and detectionwithout reducing the specificity, therefore, this combination isrecommended their application in clinical practice

1.1.2 Diagnostic role of imaging tests

Ultrasound is an important investigative tool in screening anddiscovering cancer As a subclinical tool, it is non-invasive, common,low cost and easy-to-perform for every patients Ultrasound shows asensitivity of 33-96% and a specificity of more than 90% fordetection of HCC Ultrasound imaging of HCC shows that mostlesions are hyperechoic lesion, some are mixed echogenicity due tocentral necrosis or fibrosis

Modern medical imaging techniques include Computedtomography (CT) or Magnetic Resonance imaging (MRI)

On dynamic MR imaging typical HCC exhibits contrasthyperenhancement (wash-in) in the arterial phase and contrasthypoenhancement (washout) in the portal venous or late phase andequilibrium phases, similar to the features observed with dynamic

CT According to the practice guidelines of the Associations for theStudy of Liver Diseases in the world, liver tumor with typicalcharacteristics of HCC in dynamic contrast enhancement CT or MRIcould be diagnosed as HCC with no biopsy is required Older

people are prone to be at a high risk of developing medical disease,especially kidney failure Much attention should be paid to these oldsubjects because MRI and CT posed a risk for people with severekidney failure Diagnostic value of CT is comparable to that of MRI

in both the elderly and the young

1.1.3 Role of liver biopsy

Liver biopsy currently remains the gold standard in the diagnosis

of hepatic lesions Depending on the skills and experience ofthe operator, ultrasound-guided liver biopsy allows a sensitivity of70-90% A research demonstrated that biopsy allows cancer celldetection in 60% of cases with tumor less than 2cm

1.2 Surgical therapy of HCC

1.2.2 Hepatic resection using Takasaki’s procedure

Anatomic liver resection (Takasaki K Glissonean pedicle transection method)

Takasaki described the surgical technique based on structure ofGlisson pedicle at the hepatic hilus According to Takasaki, theliver was divided into 3 sectors for the liver as a whole and anadditional caudate area, including the right segment in Takasaki’sclassification corresponds to the posterior segment Ton That Tung’ssegmental anatomy; middle segment (corresponding to the anteriorsegment in Ton That Tung’s); left segment (equivalent to middle andlateral segment in Ton That Tung’s

At liver pedicle, hepatic artery, portal vein, and biliary ductare isolated in their extrahepatic course but enter the hepatichilum wrapped in the Glisson’s capsule, which is referred to as thehilar plate

Anatomical variation only occur under the hilar plane whereasabove this hilar system, all posterior, middle and left sectionalbranches of the Glissonean pedicle are separated constantly

Glisson pedicle division - primary branches, secondary branches,peripheral branches and cone units:

According to Takasaki, three Glisson branches of the left middle right lobes can be dissected at the hepatic hilus These are calledprimary branches Glisson’s capsule continues

-to encircle these components in the liver parenchyma firmly withoutseparation

Within the liver, the main branches split into secondarybranches in the subsegments The secondary branches, further splitinto terminal branches in more peripheral branches The terminalbranches of Glisson’s pedicle represent the smallest anatomicallyresectable part in conial shape, therefore Takasaki called it the “coneunit” In resection limits, one or more cone units of correspondingsubsegment can be resected

Hilar dissection allows an exposure to three Glisson’s pediclesequivalent to left liver, anterior and posterior segment Ligation ofGlisson’s pedicles provides ind-depth understanding of accurateborder of liver segments due to ischemic color changes of otherunexpected segment surfaces

Fig 1.1 Hilar dissection in control of three Glissonean pedicles

Advantages of hepatectomy using Takasaki’s procedure

Technical benefit: Control bleeding into liver; Identify accurately

borders of segment division; minimize bleeding upon parenchymalresection

Preservation of liver function: Avoid maximum ischemia of

remnant liver volume; Contribute to preserve future remnant volumeaccurately, mininimize hepatic failure

Oncological benefit: Anatomical hepatectomy involves

the complete removal of a liver segment or sub-segmentthat which includes tumor-bearing portal vein,

Fig 1.2 Anterior segment resection

1.2.3 Foreign studies on hepatectomy for HCC management

Doan Huu Nam conducted a study on a total of 4062 HCCpatients over eight-year period (1995-2003) at Ho Chi Minh CityOncology Hospital His findings showed that viral hepatitis occurred

in 88%, B and C co-infection in 3.8% Most patients visited hospital

at a late stage Only 8.4% were eligible for liver resection According

to the UICC classification, there were 79% of patients in stage IIIAand IIIB

Common complications and mortality rate

Intraoperative hemorrhage requiring blood tranfusion isthe major post-operative complications found in 24.5% in Van Tan’sstudy and 27.2% in Doan Huu Nam’s

Research by Van Tan revealed a surgical site infection rate of8.6%, ascites of 5.3% and liver failure of 4.6%, which is frequentlyencountered post-hepatectomy Trieu Trieu Duong reported commoncomplications including pleural effusion 13.1%, subdiaphragmaticabscess 2%, bile leak 2%, postoperative bleeding 1.16% and liverfailure 0.29%

In Van Tan’s study, there was 2.6% of the patients requiringreoperation due to bleeding and fluid leak The mortality rate was15% prior to 1970 and 3.4% after the 1970

Regarding 30‐day mortality rates, Van Tan’s study revealed thatonly 3% of surgery‐related mortalities were capture Patients diedfrom liver impairment Multi-organ dysfunction and postoperative

Fig 1.3 Cone – unit of

subsegment 5

hemorrhage Mortality rates in researches by Doan Huu Nam andTrieu Trieu Duong were 0.6% and 0.58%, respectively

Recurrence and survival

The percentage of patients who are alive one year and fiveyears after liver resection was 25% and 2.6% (Doan Huu Nam’sstudy) Meanwhile, Trieu Trieu Duong’s gave promising results withthe five-year survival rate of 46%

- Location of study: Binh Dan Hospital

- Study period: Between January, 2015 and January, 2019

2.1.1 Selection criteria

- Patients aged 60 years and over

- Patients were diagnosed with HCC based on the AmericanAssociation for Study of Liver Disease (2010) including one of thefollowing two criteria:

+ Contrast-enhanced CT and contrast-enhanced MRI found HCCnodules are typically hyperenhanced in the arterial phase and showwashout in the portal venous and delayed phase

+ Liver biopsy shows as a diagnostic confirmation of HCC

- Patients are indicated for hepatectomy according to theGuidelines of the Asia-Pacific Association for the Study of LiverDiseases 2010: No extrahepatic metastasis, no invasion into theportal vein and guarante of liver function

In terms of liver function

Child Pugh A

Total blood bilirubin ≤ 2 mg%

Platelet count ≥ 100,000/mm3

Esophageal vein: no dilation

Hepatic volume is expected to preserve ≥ 40% of standard livervolume

Number and size of tumor

Solitary liver tumor or multiple nodules localize on the left andright liver or on the segments and subsegments that liver mass can beresected

Tumor size: tumor ≤ 5 cm and > 5 cm

Patient physical condition

Patients with ECOG 0 – 2; Patient’s physical condition isclassified by Europe and World Health Organization

2.1.2 Exclusion criteria

- Patients did not develop HCC

- Patients were lost to contact after surgery

: statistically significantly = 0.05 (95%CI)

Z: Value obtained from the Z-table corresponding to  = 0.05(Z1-α) /2=1.96)

P: Success rate of hepatectomy

d: Allowed error is 0.05

Applying the above sample size calculation formula, we cancalculate the minimum theoretical sample size of 45 patients

2.2.3 Surgical equipment and instruments

- XN 2000 Hematology Analyzer, CS-5100 Hemostasis System,CR1800 Injector Tester

- Samsung HS40 Ultrasound System,

- 64 slice GE Brivo 385 CT system

- MRI machine

- Rib pullers for hepatomy (Takasagoika, Japan); sealing system

- Monopolar electrocautery, bipolar electrocautery with waterchannel

- Satinsky vascular clamp of Glisson's pedicle and hepatic veins.Kelly forceps clamping liver parenchyma

- Harmonic ultrasonic scalpels

2.2.4 Surgical procedures

2.2.4.1 Physical examination for diagnosis of HCC

- Exploitation of clinical symptoms and risk factors

- Doing laboratory test for liver function, serum AFP and hepatitisbiomarkers

- Abdomincal ultrasound and CT scan was performed for allpatients If there is no confirmation of HCC by ultrasound and CTscan, MRI is indicated Liver biopsy is done in case there is notypical imaging on MRI

2.2.4.2 Surgical procedures of hepatectomy using Takasaki’s technique

* Patient positioning

- Patient position: The patient lies in the supine position withthe legs not crossed The surgeon stands on the patient's rightside throughout the surgery, whereas the first assistant stands on thepatient's left side and the second assistant stands the lateral position

as the surgeon

* Procedural steps

Step 1: Abdominal J-shaped incision or a bilateral subcostal incision

was made and expose the operative field

Step 2: Abdominal exploration: status of cirhossis, superficial or

deep tumors, extent of invasion

Step 3: Control bleeding into liver by dissecting Glisson pedicleusing Takasaki’s technique

Control Glisson pedicle of right and left liver

Control Glisson pedicle of anterior and posterior segments Selective ligation of Glisson pedicle assists to identilyanatomical demarcation of liver segments

Step 4: Liver mobilization

Step 5: Control bleeding out of liver

Control the right hepatic vein beyond liver parenchyma

Control the middle and left hepatic vein within liver parenchyma

Step 6: Hepatic parenchyma transection

Hepatic parenchymal resection according to the marked margin bycrushing the liver parenchyma to expose the vascular pedicles; isolatesmall vessels and biliary radicals Once the bile duct was divided,suture ligation was done

Hepatic vein resection: was perfomed after completion of liverparenchyma resection Using 5-0 Prolene thread to suture the hepaticvein.

Step 7: Control hemostasis, biliary leakage and abdominal

closure

All cases of hepatic resection followed the Takasaki’s procedure

2.2.4.4 Follow-up and postoperative care

2.2.4.5 Follow-up and post-hospital discharge follow-up appointments

2.2.5 Research criteria

2.2.5.1 General features

* Age: caculated according to years at surgical time

* Gender: male/female ratio

2.2.5.2 Clinical and subclinical features

* Clinical features: Pain, fatigue, loss of appetite, jaundice andabdominal tumor đau, mệt mỏi, chán ăn, vàng da, u bụng

* Risk factors

* Laboratory tests: Albumin, Biliubin, platelet, TQ, TCK, serumAFP features of abdominal ultrasound, CT scan, MRI and liverbiopsy

2.2.5.3 Surgical results of hepatectomy using Takasaki’s technique and some related factors

Intraoperation

- Surgical time

- Amount of blood loss (ml)

- The prevalence of patients with blood transfusion requirementand amount of transfused blood

- Distance from tumor to margin resection

- The margins contain cancer cells or not

- Pathological lesions: types of malignancy, level ofdifferentiation, microscopical cirrhosis, lymph node metastasis

- Classification of disease staging according to AJCC 2010