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MINISTRY OF EDUCATION AND TRAINING MINISTRY OF DEFENCE 108 INSTITUTE OF CLINICAL MEDICAL AND PHARMACEUTICAL SCIENCES HO VAN LINH STUDY OF THE VALUES OF MULTISLICE COMPUTED TOMOGRAPHY AND PANCREATICODU[.]

108 INSTITUTE OF CLINICAL MEDICAL AND PHARMACEUTICAL SCIENCES

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HO VAN LINH

STUDY OF THE VALUES OF MULTISLICE COMPUTED TOMOGRAPHY AND PANCREATICODUODENECTOMY WITH STANDARD LYMPHADENECTOMY IN THE TREATMENT OF CANCERS AT THE PANCREATIC HEAD REGION

Specialty: Digestive Surgery Code: 62720125

ABSTRACT OF MEDICAL PHD THESIS

Hanoi – 2022

THIS STUDY WAS CONDUCTED AT 108 INSTITUTE OF CLINICAL MEDICAL AND PHARMACEUTICAL SCIENCES

Scientific Supervisors:

1 A/Prof Dr Trieu Trieu Duong

2 A/Prof Dr Nguyen Anh Tuan

Reviewer:

1

2

3

The dissertation will be defended at thesis defense council at:

108 Institute of Clinical Medical and Pharmaceutical Sciences At day month 2022

Further reference to the thesis at:

1 Vietnam national library

2 108 Institute of clinical medical and pharmaceutical sciences library

LIST OF RELATED PUBLICATIONS

1 Ho Van Linh, Trieu Trieu Duong, Nguyen Anh Tuan (2021),

“Results of pancreaticoduodenectomy and lymphadenectomy in

the treatment of pancreatic head region cancers”, Journal of

108 - Clinical medicine and pharmacy, 16 (4), pp

59 – 66

2 Ho Van Linh, Trieu Trieu Duong, Nguyen Anh Tuan (2021),

“Values of multislice computed tomography in staging before radical

resection of pancreatic head region cancers”, Journal of 108

- Clinical medicine and pharmacy, 16 (4), pp 83 -90

INTRODUCTION

Cancer at pancreatic head region accounts for about 5% of gastrointestinal malignancies, including cancers of the head of the pancreas, ampulla of Vater, the distal common bile duct, and the duodenum

Diagnosis of this group of diseases is often difficult because the pancreas is located deep in the abdomen, which makes ultrasonagraphic investigation challenging On the other hand, determining whether a lesion is benign or malignant before surgery is also a great challenge Multislice computed tomography (MSCT) has enabled significant advances in early and accurate diagnosis of pancreatic head region cancer, which helps select the most appropriate treatment However, its value in the diagnosis of lymph node metastasis is still limited

Treatment of pancreatic head region cancer follows a multidisciplinary approach, in which radical surgery (Whipple procedure) plays a central role The International Study Group of Pancreatic Surgery (ISGPS) consensus conference agreed that

“standard lymph node dissection” is the recommended technique in the treatment of this group of diseases

At Military Central Hospital 108, since 2015, a 320-slice CT scan for preoperative staging, and a pancreaticoduodenectomy with standard lymphadenectomy have been used for the treatment of pancreatic head region cancer Therefore, we conducted the study:

“Study of the value of multislice computed tomography and pacreaticoduodenectomy with standard lymphadenectomy in

treatment of cancers at the pancreatic head region” with two objectives:

1 To determine the values of 320-slice computed tomography

in the staging of pancreatic head region cancer patients undergoing pacreaticoduodenectomy with standard lymphadenectomy

2 To assess the outcomes of pacreaticoduodenectomy with standard lymphadenectomy for pancreatic head region cancers

Chapter 1 LITERATURE REVIEW 1.1 Clinical and paraclinical characteristics of pancreatic head region cancers

1.1.1 Clinical characteristics

Pancreatic head region cancers share many common, often specific clinical manifestations Common symptoms are epigastric pain, jaundice and weight loss Vomiting, anemia or melena are occasionally present

non-1.1.2 Paraclinical characteristics

- Blood tests are also non-specific, often showing elevated liver enzymes and increased bilirubin, indicating biliary obstruction

- CA 19.9: Among many markers used in the diagnosis of

pancreatic head region cancer, CA 19.9 is the most commonly used and effective test Studies showed that the sensitivity and specificity

of CA19.9 in the diagnosis of pancreatic head region cancers were 70 - 92% and 68 -92%, respectively

- Abdominal ultrasound: Abdominal ultrasound is often the first

and valuable exam for the investigation of biliary tree and pancreatic duct dilatations

- Endoscopic ultrasound: Endoscopic ultrasound has the

advantage of examining the pancreas in close proximity through the wall of the stomach or duodenum which provides clearer image than transabdominal ultrasound, especially in case of small lesions

- Abdominal CT: The development of CT technique allows more

accurate imaging study of masses in the pancreatic region On abdominal CT, pancreatic head region cancer commonly appear as a mass growing in the pancreatic parenchyma or sometimes as an enlarged pancreas 320-slice CT scan has allowed accurate diagnosis

of vascular (coronary and cerebral) diseases With the potential to give

a precise image of an organ up to 16cm in size at a time with 0.5-mm

slice thickness, it enables the assessment of coronary artery disease and myocardial perfusion with high accuracy, which helps clinicians determine a more timely and appropriate treatment plan However, the application of 320-slice CT scan in the diagnosis of pancreatic head region cancer has not been widely studied by many authors

- Magnetic Resonance CholangioPancreatography (MRCP):

MRCP is better than CT in determining the anatomy of the biliary tree, pancreatic duct.It also help to examine the biliary tract proximal and distal to the obstruction site

- Endoscopic Retrograde CholangioPancreatography (ERCP):

This is a highly sensitive imaging method in examining the biliary tract and pancreatic duct system ERCP has a sensitivity of 92% and specificity of 96% in the diagnosis of pancreatic head region cancer

- Preoperative fine needle aspiaration and biopsy: For

pancreatic and pancreatic head region tumors with clear indications for surgery, it is not necessary to wait for a definitive diagnosis of histopathology before performing surgery Biopsy is only indicated when imaging is unclear, chronic pancreatitis or other benign pathology cannot be excluded

1.1.3 TNM classification

The American Joint Committee of Cancer (AJCC 2018) staging system is widely approved and used around the world In the group of pancreatic head region cancers, there are different staging systems of cancers of the pancreatic head, ampulla of Vater, distal common bile duct and duodenum

1.2 Pancreaticoduodenectomy with lymphadenectomy for pancreatic head region cancer

1.2.1 Indications

- Pancreatic cancer: tumor localized at the head of the pancreas

- Carcinoma of the ampulla of Vater

- Bile duct cancer: cancer of the distal common bile duct

- Duodenal cancer

- Pancreatic neuroendocrine cancer of the pancreatic head

- Adenoma of the ampulla of Vater or duodenum not resectable

“Extended lymphadenectomy” includes standard lymphadenectomy nodal stations plus dissection of all LN groups 8,

9, 12, 14, 16a2, 16b1 (regional lymphadenectomy plus dissection of para-aortic LNs and perirenal fatty tissue) (Gerota fascia)

After reviewing the literature and obtaining consensus from the expert panel, ISGPS (2014) recommended that extended lymphadenectomy should not be performed in pancreaticoduodenectomy because of absence of survival benefit In addition, groups 8p and 16b1 LN should not be dissected routinely

1.3 Values of multislice computed tomography in the diagnosis of pancreatic head region cancer

1.3.2 Lymph node metastasis (N)

CT assessment of LN metastasis has the diagnostic accuracy of 44% compared with 47% of endoscopic ultrasonography.The specificity in diagnosis of LN metastasis of CT is 25%

1.3.3 Distant metastasis (M)

Pancreatic head cancer usually presents with local invasion and peritoneal carcinomatosis However, there are many cases of spreading through vessels to the liver, lungs, and other less common organs including bones, adrenal glands, ovaries, and muscles Hepatic metastases are found in 64-80% of confirmed pancreatic cancer cases, while peritoneal metastases occur in 40-55% of cases

1.3.4 Vascular invasion

CT scan classification of vascular involvement includes 4 grades according to the tumor/vessel relationship”

- Grade 0: no tumor-vessel contact

- Grade I: vacular involvement ≤ 90o

- Grade II: vacular involvement > 90o and ≤180o

- Grade III: vacular involvement > 180o

1.4 Outcomes of pancreaticoduodenectomy with standard lymphadenectomy for pancreatic head region cancer

1.4.1 Shor-term outcomes

In the past few decades, many advances of the surgical techniques have reduced the mortality rate from 30% to less than 5% Many reports showed no mortality in the postoperative period However, postoperative complications remains high, ranging from 25% to 55%

in major centers The most common complications related to the current technique include bleeding, pancreatic fistula, and delayed gastric emptying

1.4.2 Long-term outcomes

Pancreatic cancer has a 5-year survival rate of about 20% with the group of patients receiving adjuvant chemotherapy having a better survival time than those without treatment Ampullary cancer has

more favorable long-term outcomes with the 5-year survival rate ranging from 18 to 67.7% Similarly, low-grade cholangiocarcinoma has a 5-year survival rate of 26-40% The factors influencing survival after surgery are tumor size, poorly differentiated tumor, lymph node metastasis, R1 resection and vascular and neural invasion

Chapter 2 SUBJECTS AND METHODS 2.1 Study subjects

Pancreatic head region cancer patients treated by pancreaticoduodenectomy with standard lymphadenectomy at 108 Military Central Hospital from June 2016 to June 2019

2.1.1 Inclusion criteria

- Age ranging from 18 to 75 years old with an ASA index ≤ 3

- Patients diagnosed with pancreatic head region tumor on imaging

- Preoperative staging using 320-slice CT scan with tumor classified

as resectable according to the NCCN guidelines

- Patients gave consent to surgery and to the study

- Patients undergoing pancreaticoduodenectomy with standard lymphadenectomy under a consensual surgical protocol

- Pancreatic head region cancer confirmed by postoperative pathologic report

- Equipments, surgical instruments and consumables at the 108 Military Central Hospital Operating Room

injection at 5ml/sec

- Triphasic CT protocol: arterial phase (35 seconds), venous phase (65 seconds), delayed phase (180 seconds)

- Image reconstruction with slice thickness less than 0.25mm

- Image proceessing and analysis: Axial, coronal and sagittal reconstruction with 2 to 3-mm slice thickness was obtained 3D vascular reconstruction was used to assess vascular tumor involvement and anatomical variations

- The 320-slice CT images was read by radiologists in a unified report form

2.2.3.2 Pancreaticoduodenectomy with standard

- Groups 14a, 14b: LNs along the right lateral superior mesenteric artery

- Group 17a - LNs on the anterior surface of the superior portion of the head of the pancreas; 17b - LN on the anterior surface of the inferior portion of the head of the pancreas

* Indications for surgery:

- The patient was diagnosed with pancreatic head region cancer using MSCT, endoscopic ultrasound or magnetic resonance cholangiopancreatography

- On MSCT imaging (within 4 weeks before surgery), tumor was

classified as resectable according to the guidelines of the American National Cancer Network (NCCN) - recommended by ISGPS

- Patient’s general condition allowing surgery (ASA I - III)

* Contraindications to surgery:

- Distant metastases

- Locally advanced tumor with vascular invasion which can not be resected and reconstructed (invasion of the superior mesenteric artery)

- Severe comorbidites (ASA > III)

- Patient refuses surgery

* Surgical protocol:

- Step 1: Incision and abdominal exploration

- Step 2: Kocher maneuver, exposure of the superior mesenteric vein at the inferior border of the pancreas

- Step 3: Dissection the hepatoduodel ligament, hepatic artery, and bile duct

- Step 4: Transection of the antrum

- Step 5: Resection of the first jejunal loop

- Step 6: Pancreas transection at the neck of the pancreas

- Step 7: Mobilisation of uncinate process from the superior mesenteric vessels

- Step 8: Restoration of gastrointestinal continuity

- Step 9: Hemostasis, drainage, and abdominal closure

2.2.4 Study parameters

2.2.4.1 General characteristics

- Age

- Gender

- Body mass index (BMI)

2.2.4.2 Clinical and paraclinical characteristics

* Clinical characteristics: abdominal pain, loss of appetite, weight loss, jaundice

* Paraclinical characteristics: Bilirubin TP (µmol/l), CA 19.9

* Pathologic results: disease staging using TNM classification by

- Value of MSCT in the diagnosis of LN metastasis

- Value of MSCT in disease staging using AJCC 2018 classification with postoperative pathologic results as gold standard

2.2.4.4 Outcomes of pancreaticoduodenectomy with standard

lymphadenectomy

* Technical characteristics

* Intraoperative characteristics

* Short-term outcomes:

- Post-operative hospital stay (days)

- Postoperative complications classified using 5-grade classification of Dindo et al (2004)

- Overall outcomes classified using Pham The Anh (2013) grading system

* Long-term outcomes:

- Distant complications

- Recurrence is defined as patient developing local recurrence, lymph node metastasis, or distant metastasis after surgery

- Factors influencing postoperative recurrence

- Disease-free survival time: calculated in months from the time of surgery to the time when recurrence detected

- Overall survival time: calculated in months from the time of surgery to the end of follow-up

- Survival outcomes: alive/loss of follow-up/deceased

- Examine the correlation between postoperative survival with tumor location, postoperative complications, lymph node metastasis and resection status

- The study was approved by the ethics committee

- Data collection was accurate, honest using the the above mentioned protocol

- All study subjects were explained in details about the disease, the surgical methods and all of them agreeed to participate in the study

- The study was conducted for the treatment purpose without any personal interest or harm to the study subjects

- All personal information of the study subjects was kept confidential

Chapter 3 RESULTS

From June 2016 to June 2019, there were 61 patients with pancreatic head region cancer undergoing pancreaticoduodenectomy

with standard lymphadenectomy

3.1 GENERAL CHARACTERISTICS

The mean age was 60.2 ± 7.7 years old Male patients accounted for 52%, female patients accounted for 48% The mean BMI was 21.6 ± 2.5

3.2 VALUES OF 320-SLICE MSCT IN THE STAGING OF PANCREATIC HEAD REGION CANCER

3.2.1 Tumor diagnosis

* 320-slice CT scan detected tumors with the rate of 95.1%

Table 3.11 Diagnostic value of pancreatic head tumor location Pathology

MSCT

Head location

Non-head location Total Pancreatic head

Non pancreatic head

Comments: 320-slice CT scan diagnosis of pancreatic head

tumors location had a sensitivity of 90%, specificity of 90.2%, and