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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[.]

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 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: A/Prof Dr Trieu Trieu Duong A/Prof Dr Nguyen Anh Tuan Reviewer: 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: Vietnam national library 108 Institute of clinical medical and pharmaceutical sciences library LIST OF RELATED PUBLICATIONS 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 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: To determine the values of 320-slice computed tomography in the staging of pancreatic head region cancer patients undergoing pacreaticoduodenectomy with standard lymphadenectomy To assess the outcomes of pacreaticoduodenectomy with standard lymphadenectomy for pancreatic head region cancers Chapter 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 nonspecific clinical manifestations Common symptoms are epigastric pain, jaundice and weight loss Vomiting, anemia or melena are occasionally present 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 by local excision - Intraductal papillary mucinous neoplasm of the pancreatic head 1.2.2 Lymphadenectomy in pancreaticoduodenectomy In 2014, the consensus conference of the International Study Group of Pancreatic Surgery (ISGPS) applied the nomenclature of the Japan Pancreas Society and gave the definition of "standard lymphadenectomy" in pancreaticoduodenectomy as removal of the lymph node (LN) groups 5, 6, 8a, 12b1, 12b2, 12c, 13a, 13b, 14a right lateral side, 14b right lateral side, 17a, 17b “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 1.3.1 Primary tumor (T) Multislice computed tomography (MSCT) can detect pancreatic head region tumors with a sensitivity of 75 - 100% and a specificity of 70 - 100% However, for tumors smaller than cm, the sensitivity is only 68 - 77% and the diagnosis accuracy is 77% For tumors over 2cm in size, the sensitivity can be higher than 98% 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 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 12 - Examine the correlation between postoperative survival with tumor location, postoperative complications, lymph node metastasis and resection status 2.2.5 Statistical analysis 2.2.5.1 Data collection All study parameters were collected using a unifined study protocol 2.2.5.2 Data analysis - All data were encrypted and inputted into a computer and then processed using SPSS 20.0 software - 2x2 contingency tables were used to evaluate the sensitivity and specificity of CT images with final pathologic results as the gold standard - T test used to compare means, χ2 test used for proportions, the difference was considered statistically significant when p 30 4.2 VALUES OF 320-slice CT scan IN STAGING OF PANCREATIC HEAD REGION CANCER 4.2.1 Tumor dìagnosis MSCT could detect pancreatic head region tumor in 95.1% of cases Among them, pancreatic head tumors, ampullary and distal common bile duct cancer accounted for 32.8%, 37.7%, and 24,6% of cases, respectively There were no duodenal cancer detected on preoperative CT In Le Hong Ky (2010) study, the proportion of ampullary, distal common bile duct, and duodenal cancer were 88.2%, 5.9% and 5.9%, respectively Nguyen Xuan Khai (2013 reported the sensitivity and specificity of MSCT in the diagnosis of pancreatic tumors of 96% and 100%, respectively Data shown in Tables 3.11, 3.12, 3.13 also show that 320-slice CT scan was very effective in dertermining tumor location The accuracy in diagnosis of tumor location of pancreatic head, ampulla of 21 Vater and distal common bile duct cancer cancer was 90.2%, 83,.5% and 72.1%, respectively 4.2.2 Lymph node metastasis Kulkarniv NM et al (2019) found that LNs could be easily detected on MSCT However, the accuracy of CT scan in the diagnosis of LN metastasis based on morphology and size criteria (short axis >1cm) was still limited According to the author, LN metastasis could be diagnosed on MSCT with an accuracy of 59.5% Using LN size ≥ 1.5cm can only detect 16.7% LN metastasis cases Data in Table 3.20 showed that 320-slice CT scan diagnosed LN metastasis with a sensitivity of 54.2% a specificity of 62.2%, a positive predictive value of 48.1% and a negative predictive value of 67.6% The results are similar to other authors, which proves that even with 320-slice CT scan, the preoperative diagnosis of LN metastasis is still a major challenge 4.3 OUTCOMES OF PANCREATICODUODENECTOMY WITH STANDARD LYMPHADENECTOMY FOR PANCREATIC HEAD REGION CANCER 4.3.1 Intraoperative findings Pancreaticoduodenectomy is a complicated surgery with a long operating time and significant risk of intraoperative bleeding Yeo CJ et al (2002) studied pancreaticoduodenectomy with standard lymphadenectomy in 146 cases, reporting a mean operating time of 5.9 ± 0.1 hours, mean intraoperative blood loss of 740 ± 40 ml, more than half of the patients did not require intraoperative blood transfusion The operative time in the study of Chen J S et al (2019) was 320 (150 – 480) minutes Our study showed that the mean operative time was 229.7 ± 40.9 (150 – 315) minutes, and the mean intraoperative blood loss was 286.4 ± 143.3 ml Main intraoperative complications was bleeding due to injuries to major blood vessels There were cases of hepatic artery injury, 22 cases of portal vein - mesenteric vein injury, one case of inferior pancreatico-duodenal artery bleeding, and one case of middle colic artery injury causing ischemia which eventually required colectomy 4.3.2 Short-term outcomes The overall complication rate of the current study was 55.7%, which were mostly classified as Dindo grade I, II and did not require any specific treatment (39.4%) Grade III or higher complications were encountered in 16.3% of cases There was only one case of postoperative death (grade V Dindo) Pancreatic fistula occurred in 39.3% of cases, of which the majority were biochemical fistula without any clinical significance Chen JS et al (2019) reported pancreaticoduodenectomy in 301 consecutive patients, showing that ISGPS grade B and C pancreatic fistula was present in 31 cases (10.3%) Ellis RJ et al (2019), published a multicenter study on 15,033 cases of pancreaticoduodenectomy in the US, reporting similar results Bleeding after pancreaticoduodenectomy could be from either gastrointestinal or intra-abdominal sources or sometimes both In our study, gastrointestinal bleeding occurred in 16.3%, of which 4, 9% had mild bleeding which did not require any treatment (grade A), 9.8% had grade B bleeding requiring blood transfusions and hemostatic drugs, and one case (1.6%) had grade C bleeding who failed endoscopic intervention and required a laparotomy for suture of bleeding from gastrojejunal anastomosis Intra-abdominal bleeding occurred in 11.5% of cases Among them, mild bleeding occurred in 4.9% (no treatment required), grade B bleeding occurred in patients (3.3%) requiring blood transfusion and hemostatic drugs, and two cases of grade C bleeding required relaparotony for bleeding control (3.3%) In the study, there was a delayed gastric emptying occurred in cases (6.6%), all of which were classified as grade B According to Melloul E et al (2020), patients with prolonged delayed gastric ... 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... PUBLICATIONS 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... values of 320-slice MSCT * Tumor - Location - Hepatic artery anatomical variations - Venous invasion * MSCT TNM staging - T stage - N stage - Value of MSCT in the diagnosis of LN metastasis - Value

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