Intraoperative staging of GIT cancer using Intraoperative Ultrasound

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1 Intraoperative staging of GIT cancer using Intraoperative Ultrasound Thesis For Fulfillment of MSc Degree In Surgical Oncology By Abdelhalim Salah Abdelhalim Moursi M.B.B.Ch (Cairo University ) Supervisors Prof. Dr. Mohammed Mohammed El-Saied Safa Professor of Surgical oncology National cancer institute, Cairo university Prof. Dr. Ahmed Mostafa Ahmed Mahmoud Assisstant Professor of Surgical Oncology National cancer institute, Cairo University Dr. Mohamed Samy Saied Elazab Lecturer of Diagnostic Radiology National cancer institute, Cairo University Faculty of medicine Cairo University 2015

2 Abstract The present study was designed to evaluate the role of intraoperative ultrasound (IOUS) in intrahepatic staging and the impact on surgical strategy for patients with GIT liver metastases as well as primary liver cancer. The ability to provide high resolution real-time imaging of the organ of interest, along with accurate lesion detection and characterization, has established the role of intraoperative sonography in a number of surgical procedures such as lobar and segmental hepatic resections, hepatic metastasectomy, and partial pancreatectomy or pancreatic enucleation. Introduction Intraoperative ultrasonography (IOUS) of the Gastrointestinal tract (GIT) cancer is an important imaging technique for guidance of both open and laparoscopic surgical procedures involving the GIT cancer (1). Continued advances in standard US, computed tomography (CT), and magnetic resonance imaging (MRI) have led to improvements in the preoperative staging of GIT cancer; however, the excellent spatial and contrast resolution of intraoperative US and the real-time imaging capability it provides in the setting of the operating suite make it uniquely valuable(2). Familiarity with the techniques of intraoperative US in both laparoscopic and open surgical settings and practice in interpreting intraoperative US images allow radiologists to localize and characterize lesions of the GIT and, in many circumstances, assist in defining the surgical strategy and approach(1). In general, indications for intraoperative US fall into several broad categories, including staging of GIT cancer, guidance for interventional or surgical procedures, assistance in planning the surgical approach, assistance in determining lesion resectability, and intraoperative diagnosis or detection of metastatic lesions in the liver (3). Intraoperative US is helpful for detecting pancreatic or hepatic lesions not detected at preoperative imaging, such as small metastases or multifocal neuroendocrine tumors of the pancreas (4).

3 Laparoscopic US may be performed before laparotomy, to investigate suspicions of tumor involvement of the vasculature and to exclude small hepatic metastases, thereby decreasing the chance that a patient might proceed to open surgery for lesions that are later found to be unresectable (5). The decision to perform laparoscopic or intraoperative US may be made by the surgeon alone or in conjunction with the radiologist (6). Intraoperative ultrasonography remains an important component of hepatic surgery. In addition to providing detailed visualization of intrahepatic anatomy and guidance for needle biopsy or ablation, IOUS has long been considered important for improved intrahepatic staging and lesion detection in patients undergoing liver surgery for GIT cancer metastases (7). Intraoperative ultrasonography detects additional liver metastases in 10% of patients undergoing surgery for colorectal liver metastases not detected in pre-operative CT, MRI and PET scan (8). Ultrasound, in practice, measures the mechanical properties of the tissue: indeed, tissues feature different acoustic impedance, which is the product of tissue density and ultrasound speed in passing through the tissue (13). Liver is the main site of metastases in GIT malignancy specially colorectal and pancreatic cancer. Colorectal cancer is the second leading cause of cancer-related death in the western hemisphere. Up to 70% of patients with colorectal cancer eventually develop liver metastases. In 30 40% of these patients, metastases are confined to the liver at the time of detection. Hepatic resection is the only therapeutic strategy that offers a chance of cure. In patients who undergo successful hepatic resection with curative intent, the expected 5-year survival rate is approximately 33%, and the 5-year disease-free survival rate is 22% (9). A large number of patients develop intra or extrahepatic tumor recurrence after curative resection(10). The main reason for these tumor recurrences is the presence of an undetected tumor at the time of the operation. Currently, patients undergo an extensive preoperative work-up before liver resection to define the hepatic lesions and to exclude the presence of extrahepatic disease(11).

4 Ultrasonography is used during pancreatic cancer surgery for resectability assessment and frozen-section analysis. To improve intraoperative assessment of pancreatic tumor extension, enhanced or novel intraoperative imaging technologies accurately visualizing and delineating cancer cells are necessary (41). Accurate staging of GIT cancer is important to determine prognosis and to select the most appropriate treatment. Beside assisting in treatment selection, staging also provides important prognostic information (12). Aim of the work We aim to evaluate role of intraoperative ultrasound in staging of GIT cancer including their indications, limitations, benefits and further directions. Specific objectives: 1st- Colorectal cancer: Value of IOUS is to detect liver secondaries not detected preoperativily, number, exact segments, relation to portal and hepatic vesseles 2nd- hepatobiliary pancreatic malignancy: Value is to stage the liver tumor accurately, and to find 2nd primary also, beside to assess relation of the large border line resectable pancreatic tumors to SMV, SMA, Portal vien and hepatic artery and the exact site of neuroendocrine pancreatic tumors and its relation to the pancreatic duct. 3rd- Gastroesophageal tumors: Value of IOUS is to detect liver secondries not detected preoperativily, also to document inoperability in advanced tumors tethering, adherent to or encasing major vessels

5 Results Age and sex: This is a prospective study which include twenty patients (11 males and 9 females) aged between28 and 67 with a mean of The distribution of patients according to age group is shown in table 1. Age group Number % Less than % % % More than % Table 1: distribution of patients according to age group (N=12) Type of patient's disease: Of the 20 patients included in the study, 2 cases with hepatic focal lesions (hepatocellular cancer and liver cell adenoma), 3 cases with pancreatic head cancer (in one of them a non-conclusive hepatic focal lesion in preoperative investigationswas suspected). One case had small intestinal malignancy, 2 cases the diagnosis was stomachcancer,12 cases with colorectal cancer (colonic cancer in 8 cases and rectal cancer in 4 cases). A summary of cases is in table 2.

6 No. Age Sex Diagnosis Effect of US in operative plan 1 50 Male primary hepatocellular carcinoma positive 2 28 female liver cell adenoma No effect 3 48 female pancreatic head malignant mass and a suspicious hepatic focal lesion positive 4 49 male pancreatic head malignant mass positive 5 30 female pancreatic head cyst positive 6 38 female GIST in proximal jejunum No effect 7 67 female Ascending colon malignant mass No effect 8 34 female Rectal cancer No effect 9 47 male Ascending colon malignant mass No effect female Rectal cancer No effect female Multiple colonic polyps with marked atypia and adenocarcinoma in 3 of them No effect female Rectosegmoid malignant mass No effect female Stomach cancer positive male Stomach cancer No effect

7 15 46 male Sigmoid cancer No effect female Rectal cancer No effect male Ascending colon malignant mass No effect male Ascending colon malignant mass No effect female Rectosegmoid malignant mass No effect male Rectal cancer No effect Table 2: A summary of cases Examples of the cases: Case 1: A male patient, 50 years old, diagnosed as primary hepatocellular carcinoma in segment 8 by preoperative multi-slice CT scan. Laparoscopic assessment and laparoscopic IOUS done and the liver was cirrhotic and the lesion is irresectable. Case 2: A female patient, 28 years old, diagnosed as accidentally discovered hepatic focal lesion during abdominal ultrasound. CT scan revealed a hepatic focal lesion in segment 5 likely to be liver cell adenoma (fig. 43). Exploration was done and IOUS, and excision of the adenoma was done with help of IOUS (fig ).

8 Figure 43: CT scan of liver cell adenoma. Figure 44: IOUS of segment five liver cell adenoma.

9 Figure 45: liver cell adenoma specimen. Figure 46: liver cell adenoma specimen. Case 3: A female patient, 48 years old diagnosed as pancreatic head malignant mass and asuspicious hepatic focal lesion by preoperative CT scan. IOUS revealed advanced pancreatic head large tumor invading the root of mesentery, and 3 cm intra parenchymatousmetastatic lesion. Trucut biopsy of liver lesion proved to be metastatic adenocarcinoma (fig.

10 47). Figure 47: IOUS of metastatic adenocarcinoma. Case 4: A male patient, 49 years old, presenting with obstructive jaundice. Abdominal ultrasound done and revealed dilated CBD and intrahepatic biliary radicals. ERCP done with stent insertion. Biopsy was inconclusive (inadequate sample). Multi-slice CT scan done revealing pancreatic head mass with no hepatic focal lesion.endoscopic US done showed anampullary mass infiltrating head of pancreas with peripancreatic LNs enlargement.us-guided FNAC done revealed atypical cells mostly adenocarcinoma. Dynamic MRI done (pancreatic mass with no liver metastases). Exploration done using IOUS.The mass was resectable but by bimanual examination of the liver, a right lobe hepatic nodule was detected.ious revealed no hepatic focal lesion and cirrhotic changes (fig. 48). Whipple operation was done (fig. 49).IOUS helped us to proceed in operation after we felt a hepatic nodule.

11 Figure 48: IOUS of cirrhotic nodule in the liver. Figure 49: pancreaticodudenectomy specimen.

12 Case 5: A female patient, 30 years old. CT abdomen showed a small pancreatic cyst, 1.5 cm. The relation of the cyst with the pancreatic duct couldn't evaluated by CT. there was no hepatic focal lesions. CT-guided biopsy revealed a pseudopapillary tumor of the pancreas. Endoscopic US showed a pancreatic head cystic mass with thick septations. Decision was enucleation of the cyst. Exploration done with IOUS.No hepatic focal lesion was detected. Pancreatic IOUS confirmed that the lesion is inseparable from the pancreatic duct (fig. 50). Then the decision changed to whipple operation as it was difficult to preserve the duct after enucleation. The decision changed after IOUS (fig. 51). Figure 50: IOUS of pancreatic cyst.

13 Figure 51: pancreaticodudenectomy specimen. Case 13: Female patient 58 years old.upper endoscopy was revealing a large hemorrhagic malignant looking ulcer just below the cardia, biopsy done (Adenocarcinoma grade 2).CT scan revealed no liver focal lesions. Decision was exploration and gastrectomy. Exploration done and IOUS. We found extensive large fixed mass by bimanual examination and by IOUS the mass very close to posterior abdominal major blood vessels and no hepatic focal lesion. The mass was irresectable (fig.52).

14 Figure 52: bimanual assessment in irresectable stomach tu Discussion Intraoperative ultrasonography is considered to be the imaging exploration with the highest resolution in the examination of the liver. IOUS remains an important component of hepatic surgery. In addition to providing detailed visualization of intrahepatic anatomy and guidance for needle biopsy or ablation, IOUS has long been considered important for improved intrahepatic staging and lesion detection in patients undergoing liver surgery for GIT metastases (79). It allows for a very good characterization of focal liver lesions, with both sensitivity and specificity

15 values over 90% (21). The present study was aiming specifically to address these concerns by examining the comparison between the IOUS and the preoperative multi-slice C, also to address the effect of IOUS on the decision of operation. It is very important for liver metastasis to be accurately identified at primary GIT cancer surgery to select the best treatment strategy, and knowledge of the presence of liver metastasis can help to obtain an improved prognosis by complete resection. However, conventional palpation of the liver and sufficient observation of abdominal cavity are not achievable during laparoscopic surgery, and so, it is not possible to accurately determine whether stage migration has occurred (21). Many studies have been reported that IOUS is an important tool that can be used to accurately stage colorectal liver metastases at the time of resection. Recently, there has been increasing interest in the use of contrast agents during the IOLUS of the liver to improve the detection of liver metastases. Tetsuya Itabashi, et al 2013, who did a prospective study of 148 colorectal cancer patients. Preoperative CT and/or MRI did not detect liver metastatic lesions in any of the 148 patients. 77 of the 148 patients were examined without IOUS. 71 of the 148 patients were examined with Sonazoid (contrast enhanced) IOUS. Liver metastases were identified by IOLUS or S-IOLUS in four patients (5.6%). Alessandro Ferrero, et al 2013, Conducted a study on 515 patients underwent hepatic resection for colorectal liver metastases. 1,370 lesions suspected for colorectal liver metastases were detected by preoperative imaging modalities. Intraoperatively, a total of 1,591 hepatic lesions suspected for CRLM were found intraoperatively by IOUS, with 293 new nodules. 280 of 1,578 resected CRLM were additional liver metastases (LMs) identified by IOUS (17.6 %). Of the 20 patients included in the study, in one patient, the focal liver lesions found at preoperative multi-slice CT was suspicious to be malignant lesion. By IOUS examination, the lesion met all the ultrasound criteria of malignancy and confirmed by biopsy and histopathological examination to be a metastatic pancreatic adenocarcinoma.

16 In the remaining 19 patients, IOUS didn t detect any hepatic focal lesions in comparison to the results of the pre-operative investigations. In this study, we found that IOUS detects liver metastases in one patient (5%) of the 20 patients undergoing surgery for GIT cancer, even with the use of state-of- the-art preoperative imaging. Based on these findings, IOUS is proved to have a clinically significant benefit for improved staging, even when modern preoperative imaging is used. In benign hepatic focal lesion, The relevant intraoperative anatomy and the spectrum of normal and abnormal findings are determined intraoperatively, along with the US features and artifacts that are frequently observed in the intraoperative setting. IOUS provides guidance for excision and tumor ablation, documentation of vessel patency, evaluation of intrahepatic biliary disease. In our study, IOUS assisted in excision of segment five liver cell adenoma and to provide accurate resection margins. In our study, 12 of 20 cases were colorectal cancer. During exploration and IOUS assessment of the liver, IOUS didn t detect any occult colorectal hepatic metastasis. Intraoperative ultrasonography (US) of the pancreas is an important imaging technique for guidance of both open and laparoscopic surgical procedures involving the pancreas. Continued advances in standard US, computed tomography (CT), and magnetic resonance (MR) imaging have led to improvements in the preoperative characterization of pancreatic lesions; however, the excellent spatial and contrast resolution of intraoperative US and the real-time imaging capability it provides in the setting of the operating suite make it uniquely valuable. Despite ongoing developments in diagnostic imaging, it is still problematic to differentiate tumor-like lesions of the pancreas, and the changes which become clearly distinguishable only during laparotomy. Intraoperative ultrasound is the method of choice in such situations, where no alternative diagnostic approaches are viable. High resolution imaging used in intraoperative scanning probes allows for a correct visualization of almost the entire pancreas. IOUS enables the determination of the criteria indicating the presence and location of the tumor mass, its echostructure and homogeneity, the imaging of its borders, and the presence of changes occurring beyond the

17 pancreas itself (lymph nodes, infiltration of adipose tissue, vascular walls of the gastrointestinal tract, metastases in other organs). In pancreatic surgery, we found that IOUS was superior than preoperative multi-slice CT in localizing the pancreatic lesion and in detection of the relation between the lesion and the surrounding anatomical structures. In our study one out of 3 cases of pancreatic surgery, IOUS detect the relation between the lesion and the main pancreatic duct which resulted in changing the decision of operation. In this case, the decision was enucleation of a pancreatic head cyst but IOUS examination revealed that the cyst is so near to the main pancreatic duct, as a result the decision changed to whipple operation. IOUS can affect the surgical strategy despite the state-of-the-art preoperative diagnostic tools. In many studies, IOUS can provide additional information that may alter treatment selection in patients with GIT and potentially resectable liver metastases. Stephan M, et al 2007, did a prospective study on 31 patients who were considered for resection of hepatic metastases from colorectal carcinoma. In 11 of 31 cases (35%), the additional use of IOUS altered the surgical strategy. Alessandro Ferrero, et al 2013, Conducted a study on 515 patients underwent hepatic resection for colorectal liver metastases. According to the IOUS findings, the surgical strategy was changed in 140 patients (27.2 %). Anselm Schulz, et al 2012, did a single-center, retrospective study of consecutive patients who underwent open liver resection for metastatic colorectal cancer. The preoperative operation strategy was altered in 29 out of 97 performed operations (29.8%), based on the results of contrast enhanced IOUS. In our study, we found that IOUS can influence the surgical strategy significantly. In 5 of the 20 patients (25%), the decision of operation had changed. In one case the IOUS helped us to proceed in the operation after the effect of bimanual examination (bar chart 2).

18 Category 1 Category 2 Category 3 all cases Bar chart 2: showing the effect of IOUS in surgical strategy : category 1: change in operative decision. Category 2: IOUS helped to proceed in operation. Category 3: no change in operative strategy. In conclusion, IOUS during operation for GIT tumors changed planned operation strategy in approximately 30% of the operations in most studies. Conclusion Despite tremendous advancements in preoperative oncologic imaging of the liver, GIT and pancreas with MDCT and MRI, IOUS provides essential diagnostic information during surgery, capable of changing surgical planning and patient management. Precise lesion localization, characterization, local staging, metastatic survey, clarifying indeterminate findings and searching for multifocal lesions not suspected on preoperative imaging are among the most common indications for IOUS in oncology. The liver is the intra-abdominal organ most commonly involved in metastatic disease. Colorectal cancer is the most frequent malignancy metastasizing to the liver, followed by pancreatic, esophageal, gastric, and gallbladder cancer. Recent advances in oncologic surgery have placed additional demands on radiologists to precisely define the number and location of liver metastases. This information is essential to define resectability and plan the

19 correct surgical approach. The applications for intraoperative ultrasound of the liver are vast and include tumor staging, metastatic survey, documentation of vessel patency or involvement, assessment of the biliary tree, and surveillance for metastatic disease. IOUS has proven accuracy for the detection of liver metastases, with reported sensitivity of 93.8%, specificity of 94.4%, positive predictive value of 92.0% and negative predictive value of 95.7%. Performing IOUS requires a sound knowledge of the hepatic segmental anatomy, familiarity with the intraoperative transducers and technique, and range of normal and abnormal findings in the liver. Lastly, the radiologist should be familiar with the artifacts that may be encountered in the setting of open and laparoscopic hepatic surgery. IOUS of the pancreas provides excellent spatial and contrast resolution and its real-time imaging capabilities are valuable for a variety of surgical procedures. Among its most common indications are localization of small tumors, local staging, identification of multifocal neuroendocrine tumors and regional metastatic survey. The use of laparoscopy and laparoscopic ultrasonography frequently avoids unnecessary laparotomy and attempted resections in patients with otherwise undetectable metastatic disease. The minimal morbidity and brief recovery associated with these procedures adds quality to the cancer patient's remaining life.

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