The Establishment And Clinical Application Of Diagnosis And Treatment Platform Based On Three-Dimensional Visualization Of Pancreatic Head And Periampullary Neoplasms

Research BackgroundThe diagnosis and treatment of pancreatic head and periampullary neoplasm, especially malignant tumor, should be under the model of a multidisciplinary team (MDT). In order to differentially diagnose and evaluate the tumor, MTD is combined with age, gender, general condition, clinical symptoms, complications, serology, and imaging examination results. Surgical removal of the primary lesion is the preferred treatment for pancreatic head and periampullary carcinoma. Therefore, pancreaticoduodenectomy has been the gold standard for surgical treatment. Currently, the diagnosis in most of the national hospitals for pancreatic head and periampullary carcinoma is still based on the clinical symptoms and imaging results including US, CT, MR, MRCP, and EUS, which are significant in this procedure. Because every imaging method has its advantages and disadvantages, surgeons always use multiple ways to improve the accuracy rate of diagnosis. As is well-known, most imaging data is planar; even advanced CT and MR can complete 3D reconstruction. To achieve the diagnosis of the disease, surgeons need to switch the two-dimensional imaging conceptually into three-dimensional structures based on experience. Hence, errors are inevitable.In recent years, the rapid development of digital medical technology is expected to make up for the inadequacy of traditional imaging technology. Digital medical technology is the extension of digitalized virtual human study. It is the application science in order to explain medical phenomenology, resolve medical problems, explore the healing mechanisms, and improve the quality of life eventually.Three-dimensional visualization is the important part of digital medical technology. In recent years, studies of 3D visualization have been conducted exhaustively in nerve surgery, gynecology and obstetrics, orthopedics, plastic surgery, and general surgery and have been applied in clinical practices. The technique can acquire and establish the 3D model preoperatively, which is replicative of the abdominal organs and blood vessels of patient’s actual anatomy. It also provides the hepatobiliary surgeon with the individual morphological basis that can help them rationally select the operation scheme and prevent the postoperative complications. However, investigations on the 3D visualization in surgical diagnosis and treatment for pancreatic head and periampullary carcinoma is yet in primitive, very few cases of clinical trials reports exist. Therefore, it is necessary to construct a 3D visualization platform in the diagnosis and treatment of pancreas and periampullary carcinoma, then carry out demonstrative clinical application research. The project aims to study the new three-dimensional reconstruction method and build a high-quality pancreas and periampullary carcinoma model using the Medical Image Three-Dimensional Visualization System based on high-quality submillimeter CT data.ResMan clinical trials public management platform was used to establish the database of the pancreas and periampullary carcinoma, and 3D visualization diagnostic and therapeutic platform as well as the management process. According to a retrospective study, we can compare the accuracy of MI-3DVS in a preoperative diagnosis and evaluate the clinical effect of 3D visualization technology assisted pancreaticoduodenal resection of pancreatic head and periampullary carcinoma. We can further assess the application value of 3D visualization technology assisted "one-thread" pancreaticojejunostomy in pancreaticoduodenectomy to prevent pancreatic fistula. According to the above method, we can systematically evaluate the clinical application value and significance for the establishment of 3D visualization platform in the diagnosis and treatment of pancreatic head and periampullary carcinoma.Part Ⅰ. The establishment of three-dimensional visualization platform in the diagnosis and treatment of pancreatic head and periampullary neoplasmsObjectives1. To optimize the CT data acquisition method for the acquisition of high-quality sub-millimeter CT data in the cases of pancreatic carcinoma and periampullary neoplasms.2. Investigating new 3D reconstruction method based on surface and volume rendering, which could construct a high-quality 3D model of the pancreatic carcinoma and periampullary neoplasms effectively.3. ResMan clinical trials public management platform was used to establish the database of the efficacy analysis in the treatment of pancreas and periampullary carcinoma, based on 3D visualization.4. Establishing the three-dimensional visualization platform in the diagnosis and treatment of pancreatic head and periampullary neoplasms and formulating its management process as well as evaluating its clinical application.Methods1. The clinical data of 95 patients (45 males and 50 females with an average age of 55.8 years) with pancreatic head and periampullary neoplasms from Zhujiang Hospital, Southern Medical University, China, were retrospectively and systematically collected from October 2008 to December 2015; 64 rows/256 slice CT.2. The acquisition devices of the CT data include 64 rows/256 slice CT by a spiral CT scanner (CT PHILIPS Brilliance, Netherlands), double tube high pressure syringe, contrast agents (Lopamiro in a dose of 370 mg/mL), the self-attached Mxview workstation for post-processing of the images, HP blade server and high configuration computer (Clinical Center of Digital Medicine, Southern Medical University, Guangzhou, China), the abdominal three-dimensional visualization system, and medical image visualization processing system (3D+).3. The procedures for collecting high-quality submillimeter CT data of pancreatic carcinoma and periampullary neoplasms include pre-scanning preparation, plain scanning, trial injection, routinely enhanced scanning as well as the transmission and storage of thin layer CT scanning data (Fang et al.,2013).4. Reconstruction method of 3D model for the cases of pancreatic carcinoma and periampullary neoplasms:(1) Rapid reconstruction based on surface rendering:Surface rendering was used for pancreas, tumor, bile duct, and pancreatic duct, through seed point region expanding to segment data. For larger imaging data, the "box" tool which can select the region of interest can reduce the amount of data and accelerate the process.(2) Fractional and assembling reconstruction based on surface rendering:Slight differences in the CT threshold between pancreas, tumor, bile duct, pancreatic duct, and adjacent tissues could instigate errors such as deformation and partially missed occurrence to the reconstructed model. In order to complete the process, the structures can be reconstructed gradually and assembled.(3) Individual segmentation and reconstruction of carcinoma:Selection of enhanced scanning data with a larger difference with the adjacent tissue, for reconstruction.(4) Reconstruction of celiac artery system was based on the combination of volume and surface rendering. Also, the seed region growing is useful for the segmentation for portal vein system.(5) Post-processing of the 3D model:3D model was smoothed and denoised by image processing tools.(6) Verification of the accuracy of the 3D model:Two surgeons were required to observe the integrating degree from the stereo and multi angle to verdict whether the 3D model reflects the CT data accurately and presents the actual anatomic structures through the fusion display of 3D model and CT images.(7) Three-dimensional quantitative analysis based on the 3D model:The 3D model for pancreas, liver, tumor, biliary and pancreatic duct, celiac artery, and portal vein system were displayed through amplification, narrowing, and rotation to reveal the 3D structure of abdominal viscera and vascular structure.By analyzing the characteristic of the 3D reconstructed model of pancreatic head and periampullary neoplasms, the position and size of the tumors, dilatation degree and variation of bile and pancreatic duct, spatial relations between the tumor and the celiac and portal vein system can be observed. Concurrently, with the aid of the tools for angle and length measurement, and simulated incision, we can analyze the region of interest quantitatively and acquire accurate 3D data. In addition, we can evaluate the integrity of the tumor according to pancreatic head and periampullary neoplasms classification criteria.5. Three-dimensional visualization and 3D printing of pancreas:In complicated cases of pancreatic head and periampullary neoplasmss, which present a proximate association of the tumor and the portal vein, superior mesenteric vein and superior mesenteric artery, the pancreas 3D visualization and 3D printing can provide secondary navigation and guide definitive surgical resection.6. The establishment of the three-dimensional visualization platform in the diagnosis and treatment of pancreatic head and periampullary neoplasms:(1) Formulating the management process of the three-dimensional visualization platform in the diagnosis and treatment of pancreatic head and periampullary neoplasms.(2) Preparing the case record form (CRF) including the baseline data and hematology, imagology examination,3D images data as well as other diagnosis and treatment information.(3) Establishing the three-dimensional visualization database in the diagnosis and treatment of pancreatic head and periampullary neoplasms:Apply for clinical data for setting up a database management according to the clinical research at the Chinese Clinical Trial Center and registering the clinical trial.Results1. The quality of submillimeter CT images obtained via trial injection was optimal, with favorable demonstrations of the pancreatic lesions, peripheral arterial lesions of the carcinoma, bile duct lesions, and pancreatic duct lesions.2. The 3D model of pancreatic head and periampullary neoplasms of 95 patients can be multi-dimensionally rotated to demonstrate clearly the 3D shape of the pancreas and the anatomical characteristics. The 3D model can also clarify the obstruction location through the demonstration of carcinoma, dilated bile ducts, and pancreatic ducts. The reconstructed peripancreatic blood vessel including coeliac trunk artery (CTA), common hepatic artery (CHA), proper hepatic artery (PHA), splenic artery (SA), gastroduodenal artery (GDA), right gastroepiploic artery (RGA), superior mesenteric artery(SMA), portal vein (PV), superior mesenteric vein (SMV), splenic vein (SV) can be presented vividly. The function of combination, separation, rotation, and stereoscopic observation provides a clear image of the liaison between the carcinoma and peripancreas blood vessel, organ, and tissue.3. Three-dimensional visualization printing model of complicated pancreatic head and periampullary neoplasms of 8 patients was according to the 3D visualization model and original CT data. The printing model can be utilized in the operating room for comparison with the real time operation and provide instant operative navigation, rapid identification, and orientation of the critical tissue.4. The clinical database of diagnosis and treatment in pancreatic head and periampullary neoplasms cases with the aid of 3D visualization has been constructed successfully as a publicly accessible database based on ResMan clinical trials public management platform. The development of database management procedure and the design of case record form (CRF) was carried out according to the clinical features of the pancreatic head and periampullary neoplasms for the storage and management of data for improved reliability and quality of clinical trials. The public accessible database of diagnosis and treatment in pancreatic head and periampullary neoplasms cases with the aid of 3D visualization has fulfilled the requirements of the Chinese Clinical Trial Center and completed the registration of clinical trials successfully.5. The three-dimensional visualization platform in the diagnosis and treatment of pancreatic head and periampullary neoplasms was established, which focused on the 3D visualization and printing technology with the data management and analysis platform for ResMan database.Conclusions1. High-quality submillimeter CT data can provide high-resolution imaging features of abdominal organs and blood vessels, and hence, can be used to modularize the 3D model reconstruction.2. The 3D model of pancreatic head and periampullary neoplasms and the 3D printing model can clarify the shape and location of the tumor, The obstruction location and dilation degree of bile and pancreatic duct, pancreatic pathology, morphological changes, spatial relationship of carcinoma and blood vessels, help the surgeon make accurate, systematic, and comprehensive diagnosis and assess the resectability of carcinoma.3. Three-dimensional visualization platform in the diagnosis and treatment of the patient with pancreatic head and periampullary neoplasms possesses scientific nature, rationality, and advancement. Therefore, it may demonstrate further clinical potential.4. Three-dimensional visualization platform in the diagnosis and treatment of the patient with pancreatic head and periampullary neoplasms possesses scientific nature, rationality, and advancement. Therefore, it may demonstrate further clinical potential.Part Ⅱ The clinical value of 3D visualization technology assisted pancreaticoduodenectomy in the treatment of pancreatic head and periampullary neoplasmsObjective1. To assess the advantage of the Three-Dimensional Visualization System (MI-3DVS or 3D) in the diagnosis of pancreatic head and periampullary neoplasms.2. The aim of the study was to evaluate the clinical value of 3D visualization technology assisted pancreaticoduodenectomy in the treatment of pancreatic head and periampullary neoplasms.Methods1. Study subjects:The clinical data were extracted from the ResMan clinical trials of public management platform as described above in part Ⅰ.71 patients,37 males and 34 females with an average age of 56.9±12.9years, with pancreatic head and periampullary neoplasms between October 2008 to December 2015 at the Department of Hepatobiliary Surgery, Zhujiang Hospital, were analyzed. These cases were assigned to 3D visualization group (group A). Also, the clinical data of 80 patients,37 males and 51 females with the age of 59.2±11.4years, with pancreatic head and periampullary neoplasms subjected to pancreaticoduodenal resection without 3D visualization technology were collected during the same period, and defined as a control group (group B). No significant differences were found between the two groups with respect to the clinical data including sex, age, comorbid illness, and laboratory tests.2. Inclusion criteria(1) aged 18 or above, (2) conformed to the definition of pancreatic head and periampullary neoplasms, (3) liver function classified in Child-Pugh A or B, and (4) underwent pancreaticoduodenectomy.3. Data collection(1) US:Philips Ultrasound ATL HDI 3500/5000 with a 2.5-5.0 MHz transducer frequency is adopted. A 7-9 h fasting was a prerequisite before the examination. Supine and left lateral position should be posed by the objective. Regular examinations of the liver, biliary system and pancreas were conducted as well as the dynamic association of the diseased region and surrounding structure was monitored. The representative images were deposited into Ultrasound image workstation.(2) MR:Philips Archieva 1.5/3.0T MRI scanner was employed in this study. All patients were examined with the plain scan, enhanced scan, and MRCP after 8-12 h fasting. Firstly, a regular plain scan was carried out in the supine position. T2W1 imaging with FSE sequence respiratory gating in axis and the coronary position was included. Scanning parameters were as follow:TR:8000-16000 ms, TE:200-252 ms, scanned area:24-36cm, matrix:512×192, slice thickness:2-5 mm, layers:30-60, the number of excitations:2, scanning time:4-6 min. MRCP was implemented right after the plain scan. All data were collected in a breathless period. The whole analysis takes about 15-20 min.(3) The procedures for submillimeter CT data collection and 3D reconstruction were the same as described in part I.4.The individual morphological classification and the diagnosis evaluation of pancreatic head and periampullary neoplasms based on 3D visualization technology through MI-3DVS(1) Individual morphological classification diagnosis of pancreatic head and periampullary neoplasms was conducted associated with multiple factors. The 3D reconstruction images could be amplified, rotated, and casually assembled to clarify the anatomic characteristics of the tissue structures with omnidirectional, multiple-angle, and multilevel views. This can provide more intuitive and omnidirectional information of tumor localization, distal common bile duct stenosis, extrahepatic bile duct distention, main pancreatic duct dilatation, and pancreatic atrophy.(2) The categorization of the pancreatic head and periampullary neoplasms based on 3D visualization technology through MI-3DVS (Fang et al.,2012).5. Loyer et al. method is followed for the evaluation of pancreatic head and periampullary neoplasms based on CT technology (Loyer et al.,1996).6. Image analysis methodThe image analysis personnel did not realize the clinical prognosis and other imaging examination results. The major assessment criteria of Single-Blind Peer Review for image analysis consists of:(1)the localization of tumor, (2) the existence of the bile duct distention, (3) the existence of the pancreatic duct dilatation, and (4) the presence of pancreatic atrophy. The following statistical indicators were adopted for the evaluation of the diagnosis of pathological alterations through different examination methods:sensitivity, specificity, accuracy, positive predictive value, negative predictive value, Youden index and Kappa value.7. Evaluation indicators(1) Surgical planning of pancreatic head and periampullary neoplasms with the aid of three-dimensional visualization technology:The pancreas, liver, tumor, bile duct, pancreatic duct, celiac artery system, and portal vein system can be amplified, narrowed, rotated and hyalinized in the 3D model. The anatomical features and association of pancreas and blood vessels of the peripancreatic head region can be viewed through omnidirectional, multiple-angle, and multilevel MI-3DVS. Also, individual morphological classification diagnosis and assessment of pancreatic head and periampullary neoplasms can be performed through MI-3DVS. Simulated operations can be conducted on the 3D reconstructed model through the MI-3DVS system-attached tools, including 3D cutting,3D length measurement, and 3D angle measurement. The optimal surgical approach was determined after repetitive simulated cutting and measurements, which can predict the possible injury of blood vessels and avoid accidental bleeding.(2) The evaluation of surgical treatment:A laptop for reading the 3D model was allowed into the operating room for real-time intraoperative surgical guidance and adjustment of the approach. When the surgical procedure was performed closely to the large blood vessels, the reference of 3D model can avoid the unnecessary vascular damage and bleeding by changing the operative path.Evaluation indicators of operation process:operation time, intraoperative blood loss volume, intraoperative blood transfusion volume, intraoperative abnormal bleeding (injury of the major vessel in the peripancreatic head region), and abdominal drainage on the first postoperative day.Evaluation indicators of perioperative effect: ①postoperative laboratory data:liver function; ﹑ostoperative symptoms:jaundice, fever, abdominal pain;③incidence of postoperative complications:pancreatic fistula (grade A, grade B, grade C), biliary fistula, hepatic function failure, delayed gastric emptying, pancreatitis, abdominal abscess, abdominal bleeding, gastrointestinal anastomosis bleeding, gastrointestinal hemorrhage, pleural effusion, infection of incision, the second operation;④ postoperative hospitalization time, perioperative mortality.8. Statistical analysisContinuous variables were expressed as mean ± standard deviation and compared using the Student’s t-test whereas categorical variables were compared using Chi-squared test and Fisher’s exact tests. P<0.05 was considered statistically significant. All statistical analyzes were performed using SPSS13.0.Results1. Clinical diagnostic outcomes of 3D model in pancreatic head and periampullary neoplasms.Precise segmentation and reconstruction for tumor, abdominal blood vessel, biliary and pancreatic duct, and other abdominal organs as well as blood vessels can be performed through MI-3DVS in the pancreatic head and periampullary neoplasms. 71 cases obtained stereo and legible 3D images of the pipe system in the pancreas and peripancreas region,morphological change of pancreas, the location and size of tumor, the morphology of extrahepatic bile duct (distal bile duct stricture, length, and diameter of expansion of the bile duct) as well as the distribution and branches of portal vein system and celiac artery system. Individual morphological classification diagnosis of pancreatic head and periampullary neoplasms based on 3D visualization technology were in accordance with intraoperative probe findings.2. Comparison of diagnostic outcomes of different imaging examination methodsThe overall accuracy of MI-3DVS in the judgment of location of the tumor was significantly higher than US (P=0.000), CT (P=0.001) and MR (P=0.003). The accuracy of clinical diagnosis in the existence of extrahepatic bile duct dilatation in MI-3DVS was significantly higher than US (P=0.000) and CT (P=0.037), but there was no significant difference between MI-3DVS and MR(P=0.476). Both PPV and NPV in the estimation of the existence of main pancreatic duct dilatation with MI-3DVS were 100%, and its accuracy was significantly higher than US (P=0.000), but there was no significant difference between CT (P=0.128) and MR(P=1.000). The accuracy of clinical diagnosis in the existence of pancreatic atrophy in MI-3DVS was significantly higher than US (P=0.034), but there was no significant difference between CT (P=0.346) and MR(P=0.346). The accuracy in the diagnosis of the pathological changes in MI-3DVS was similar to intraoperative exploration results by means of Youden index and Kappa value.3. The clinical results of 3D visualization technology assisted pancreaticoduodenectomy.The overall accuracy of evaluation with the aid of 3D visualization technology was significantly more than that based on CTA (100% vs 87.4%, P=0.002). The operation time in group A was significantly shorter than the group B (291.6±75.6 min vs 324.8±102.4 min, P=0.026). The blood loss volume in group A was significantly lower than that in group B (479.5±384.5mL vs 718.7±444.7mL, P=0.001). The abnormal bleeding in the peripancreatic head region was significantly less in group A than in group B during the excision of the exploratory process (4.2% vs 15%, P=0.031). There was no significant difference in indicators during the perioperative period.Conclusion1.3D model of the pancreatic head and periampullary neoplasms based on MI-3DVS clearly demonstrated the morphology of pancreas, the shape, size, and location of the tumor as well as the degree of pancreatic duct expansion and extrahepatic bile duct stenosis or expansion. It also presented the anatomic association of pancreas, tumor, and peripheral vasculature, thus reducing the fuzziness and instability of the virtual imagination in surgeons, Therefore, the risk of bleeding, pancreatitis, and cholangitis induced by invasive procedures such as ERCP can be avoided.2. MI-3DVS can be used as a supplement and innovative method for the diagnosis and treatment of pancreatic head and periampullary neoplasms.3. The 3D visualization technology can be used for preoperative surgical planning, optimization of surgical exploration path, shortening of the operation time, reducing intraoperative bleeding and improving resectable rate of pancreatic head and periampullary neoplasms.Part Ⅲ "One-thread" pancreaticojejunostomy under three-dimensional visualization guidance:A novel technology to prevent pancreatic fistula in pancreaticoduodenectomyObjectiveTo investigate "one-thread" pancreaticojejunostomy under three-dimensional (3D) visualization guidance in order to prevent pancreatic fistula.Methods1. Study subjects:As described in part Ⅲ, the clinical data of the patients in group A underwent "one-thread" pancreaticojejunostomy were extracted through the ResMan clinical trials of public management platform (part Ⅰ).37 cases (group C),21 males and 16 females, with the median age of 52 years (range 31-70), from Janurary 2012 to December 2015, were analyzed. Among the 37 cases,15 were a pancreatic head carcinoma,7 cases of distal bile duct carcinoma,9 lower bile duct cancer,9 cases of periampullary carcinoma, and 6 cases of duodenal papillary carcinoma. Patients with benign diseases were not included in this study.2. The required equipment, the methods for collecting and CT segmentation data, as well as the three-dimensional reconstruction method, were consistent with the part Ⅰ.3. Patients underwent digestive reconstruction with "one-thread" pancreaticojejunostomy in the process of pancreatoduodenectomy.4.Three-dimensional reconstruction and evaluation of resectability:3D model could be optionally assembled and displayed for preoperative diagnosis and evaluation of resectability. The main observation elements include:shape, size and, location of the tumor, peripancreatic head region vascular distribution and morphology, analysis of pancreatic canal anatomical characteristics, precise positioning of the pancreas tube, measurement of pancreatic pipe diameter, and the measurement of pre-resection pancreatic stump diameter that is determined as, pancreatic stump diameter= (upper and lower diameter+left and right diameter)/2. Also, the categorical classification was conducted based on MI-3DVS.5. Surgical methodsWe adopted the "one-thread" pancreaticojejunostomy in this study as described by Xian et al. (Xiang et al.,2014).6. Evaluation method of postoperative complicationsClassification and assessment of pancreatic fistula and delayed gastric emptying (DGE) were according to the international pancreatic fistula research group (ISGPF). Postoperative complications were evaluated according to Clavien-Dindo grading standard; grade Ⅲ and above was included in the incidence of postoperative complications.7. Statistical treatmentAll statistical analyzes were performed using SPSS 13.0. Continuous variables were compared using t-test. P<0.05 was considered statistically significant.Results1. The results of classification assessment of resectability:type Ⅰ:47; type Ⅱ:11, type Ⅲ:2.2. The diameter of the main pancreatic duct was 2.9+1.3 mm, and the diameter of the pancreatic stump was 3.8+0.4 cm, which was consistent with the results of operative exploration (P>0.05). Simultaneous expansion of the main pancreatic duct and the pancreatic duct occurred in 3 cases (8.1%).3.With the operation time of 15 min (range 10-26 min), the anastomotic method of "one-thread" pancreaticojejunostomy was successfully performed in 37 patients. The incidence of pancreatic fistula was 5.4%(2/37) and was classified as grade A. Abdominal bleeding, biliary fistula, and other complications, as well as mortality, did not occur. Postoperative hospital stay was 11 d (range 7-17 d).Conclusions"One-thread" pancreaticojejunostomy with the aid of 3D visualization technology is a simple handling method with solid anastomosis, thus designated as a safe and efficient technique for the prevention of postoperative pancreatic fistula in pancreaticoduodenectomy.