Generation and application of patient-derived xenograft models in pancreatic cancer research / 中华医学杂志(英文版)

OBJECTIVE@#Pancreatic ductal adenocarcinoma cancer (PDAC) is one of the leading causes of cancer-related death worldwide. Hence, the development of effective anti-PDAC therapies is urgently required. Patient-derived xenograft (PDX) models are useful models for developing anti-cancer therapies and screening drugs for precision medicine. This review aimed to provide an updated summary of using PDX models in PDAC.@*DATA SOURCES@#The author retrieved information from the PubMed database up to June 2019 using various combinations of search terms, including PDAC, pancreatic carcinoma, pancreatic cancer, patient-derived xenografts or PDX, and patient-derived tumor xenografts or PDTX.@*STUDY SELECTION@#Original articles and review articles relevant to the review's theme were selected.@*RESULTS@#PDX models are better than cell line-derived xenograft and other models. PDX models consistently demonstrate retained tumor morphology and genetic stability, are beneficial in cancer research, could enhance drug discovery and oncologic mechanism development of PDAC, allow an improved understanding of human cancer cell biology, and help guide personalized treatment.@*CONCLUSIONS@#In this review, we outline the status and application of PDX models in both basic and pre-clinical pancreatic cancer researches. PDX model is one of the most appropriate pre-clinical tools that can improve the prognosis of patients with pancreatic cancer in the future.

Generation and application of patient-derived xenograft models in pancreatic cancer research / 中华医学杂志(英文版)

Objective@#Pancreatic ductal adenocarcinoma cancer (PDAC) is one of the leading causes of cancer-related death worldwide. Hence, the development of effective anti-PDAC therapies is urgently required. Patient-derived xenograft (PDX) models are useful models for developing anti-cancer therapies and screening drugs for precision medicine. This review aimed to provide an updated summary of using PDX models in PDAC.@*Data sources@#The author retrieved information from the PubMed database up to June 2019 using various combinations of search terms, including PDAC, pancreatic carcinoma, pancreatic cancer, patient-derived xenografts or PDX, and patient-derived tumor xenografts or PDTX.@*Study selection@#Original articles and review articles relevant to the review’s theme were selected.@*Results@#PDX models are better than cell line-derived xenograft and other models. PDX models consistently demonstrate retained tumor morphology and genetic stability, are beneficial in cancer research, could enhance drug discovery and oncologic mechanism development of PDAC, allow an improved understanding of human cancer cell biology, and help guide personalized treatment.@*Conclusions@#In this review, we outline the status and application of PDX models in both basic and pre-clinical pancreatic cancer researches. PDX model is one of the most appropriate pre-clinical tools that can improve the prognosis of patients with pancreatic cancer in the future.

Development of laparoscopic technology in biliary surgery in the past 23 years: a single-center experience / 南方医科大学学报

<p><b>OBJECTIVE</b>To summarize the 23-year experience of laparoscopic biliary surgery in General Hospital of PLA and evaluate the application of laparoscopic surgery in the treatment of biliary diseases.</p><p><b>METHODS</b>We retrospectively analyzed the clinical data of 11 419 consecutive patients with biliary diseases undergoing laparoscopic surgery from April, 1992 and December, 2014. The disease spectrum was compared between patients treated before December 31, 2003 and those treated after the time point.</p><p><b>RESULTS</b>The 11419 patients receiving laparoscopic surgery accounted for 56.3% of the total patients undergoing biliary surgeries during the 23 years, including 4701 male and 6718 female patients with a mean age of 50.9∓13.2 years (6-93 years). Most (80.83%) of the patients received laparoscopic surgery for gallbladder stones, and 12.53% patients had the operation for gallbladder polyps. The laparoscopic operation rate was 84.81% in patients with gallbladder stones and 34.91% in patients with extrahepatic bile duct stones, but remained low in patients with biliary carcinoma. In laparoscopic operations, laparoscopic cholecystectomy was the most frequent (96.18%) followed by operations for extrahepatic bile duct stones, in which primary suture accounted for 1.38%, traditional T tube drainage for 0.90% and laparoscopic transcystic duct exploration for 0.72%. For malignant tumors, laparoscopic technique was used mainly for the purpose of exploration (0.34%). The application of laparoscopic technique in biliary surgery tended to increase after the year 2004, especially for benign gallbladder diseases and extrahepatic bile duct stones (P<0.05).</p><p><b>CONCLUSION</b>Laparoscopic technique in biliary surgery is gradually replacing the traditional open operation and becomes the gold standard for the treatment of benign biliary diseases.</p>

Clinicopathological characteristics and prognosis of solid pseudopapillary neoplasm of the pancreas: comparison between tumors ≤5 cm and larger tumors / 南方医科大学学报

<p><b>OBJECTIVE</b>To compare the clinicopathological characteristics and prognosis of patients with small (≤5 cm) solid pseudopapillary neoplasm of the pancreas (SPN) and those with large (>5 cm) SPNs.</p><p><b>METHODS</b>We retrospectively analyzed the clinical characteristics, laboratory findings, radiological features, treatment and prognosis of 148 patients with histologically confirmed SPN between August, 2006 and December, 2014 and compared the data between patients with small SPNs (≤5 cm) and those with large SPNs (>5 cm).</p><p><b>RESULTS</b>In the large SPN group, the female-to-male ratio was significantly higher than that in small SPN group (61/8 vs 56/23, P=0.009) and the patients were significantly younger in large SPN group (28.3±12.3 vs 33.0±11.4 years, P=0.016). Small SPNs (≤5 cm) typically presented as inhomogeneous solid or cystic tumors, while large SPNs (>5 cm) often appeared as homogeneous solid and cystic tumors, but they did not show any significant difference in aggressive behaviors (P=0.288). The 5-year disease-free survival of patients with small SPNs was 100%, and the 1-, 3-, and 5-year disease-free survival of patients with large SPNs was 98.6%, 94.9%, and 89.3%, respectively (P=0.030), showing no significant differences in the overall survival between the two groups.</p><p><b>CONCLUSION</b>Small SPNs and large SPNs have different clinical characteristics. Even with complete resection, tumors larger than 5 cm are more likely to have tumor recurrence and metastasis, and close follow-up is recommended for these patients.</p>

Clinicopathological characteristics and prognostic factors of intrahepatic biliary cystadenocarcinoma / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Surgical resection is generally considered the main curative treatment for intrahepatic biliary cystadenocarcinoma (IBCA) or suspected IBCAs, but controversy exists regarding the prognosis for IBCAs. This study aimed to describe the clinicopathological characteristics of IBCA and identify prognostic factors that may influence the survival of patients treated with surgical procedures.</p><p><b>METHODS</b>Thirty-four patients with histologically confirmed IBCA treated between January 2000 and June 2014 were included. The clinical characteristics of patients with IBCA were compared with those of 41 patients with intrahepatic biliary cystadenoma (IBC); factors that significant difference were analyzed for prognosis analysis of IBCA using multivariate/univariate Cox proportional hazards regression models. Survival curves were constructed using the Kaplan-Meier method and compared using the log-rank test.</p><p><b>RESULTS</b>IBCAs had a strong female predominance, and the most common presenting symptoms were abdominal pain or discomfort. Compared with IBCs, IBCAs occurred in older patients, in more male patients, and were associated statistically significant abnormal increase in alanine aminotransferase (P = 0.01) and total bilirubin (P = 0.04). Mural nodules were more frequently seen with IBCAs and may associate with malignancy. It was difficult to differentiate between IBC and IBCA based on laboratory examination and imaging findings. Although complete resection is recommended, enucleation with negative margins also achieved good outcomes. Median overall patient survival was 76.2 months; survival at 1, 3, and 5 years was 88.0%, 68.7%, and 45.8%, respectively. Radical resection and noninvasive tumor type were independent prognostic factors for overall survival.</p><p><b>CONCLUSIONS</b>It remains difficult to distinguish between cystadenomas and cystadenocarcinomas based on laboratory examination and image findings. Complete resection is recommended for curative treatment, and patients should be closely followed postoperatively, particularly those with invasive tumors.</p>

Technical points of total laparoscopic choledochal cyst excision / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Choledochal cyst excision and biliary enteric reconstruction constitute the best therapy for choledochal cyst. And laparoscopy is currently used to cure this disease now.</p><p><b>METHODS</b>We retrospectively analyzed the clinical data of 34 cases of total laparoscopic choledochal cyst excision between January 2007 and August 2011. All patients underwent in vitro Roux-en-Y hepatoenterostomy.</p><p><b>RESULTS</b>All 34 patients underwent successful total laparoscopic choledochal cyst excision. The operation time was 200 - 360 minutes. The duration of hospital stay was 3 - 7 days. Follow-up observations lasted 1 - 56 months. One patient developed an anastomotic stoma stricture, but no other cases had postoperative complications. No patients died.</p><p><b>CONCLUSION</b>Total laparoscopic choledochal cyst excision is safe and feasible.</p>

Effect of resection following downstaging of unresectable hepatocelluar carcinoma by transcatheter arterial chemoembolization / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>This retrospective study was undertaken to analyze the outcome of hepatic resection in fifty-two patients with unresectable hepatocellular carcinoma (HCC) between January 2004 and December 2008.</p><p><b>METHODS</b>Among these fifty-two patients, the mean diameter of the tumor was 7.9 cm (4.4 - 15.5 cm, median 8.5 cm) prior to the first transcatheter arterial chemoembolization (TACE). After 1 - 6 times of TACE (median 2), the median tumor diameter was reduced to 4.2 cm (0 - 8.4 cm) prior to resection. The duration between the last TACE treatment and sequential resection varied from one to six months (median 2.7 months). Serum a-fetoprotein (AFP) levels were abnormal in thirty-eight out of the fifty-two patients. In AFP producing HCCs, AFP levels returned to normal (≤ 400 µg/L) in twenty-five out of thirty-eight patients. Hepatic segmentectomy, multiple hepatic segmentectomy or partial hepatic resection were performed in forty-five patients, two underwent extended left hemihepatectomy, and one underwent right posterior branch portal vein thrombectomy. One patient received a right hemihepatectomy and three had left hemihepatectomies.</p><p><b>RESULTS</b>Complete tumor radiological response (CR) occurred in five patients (9.6%). There were three cases of perioperative mortality in the fifty-two patients (5.8%). One patient underwent salvaged orthotopic liver transplantation, and twenty-one patients observed tumor recurrence within two years. The 1-, 3- and 5-year survival rates of the fifty-two patients were 77.0% (n = 40), 55.0% (n = 29), and 52.0% (n = 28), respectively. The median survival time after surgery was 49 months (95% confidence interval 7.5 - 52.7 months).</p><p><b>CONCLUSIONS</b>TACE treatment provides a better chance for HCC resection in patients initially diagnosed with unresectable HCC. Furthermore, liver resection should be performed once the tumor is downstaged to be compatible for successful resection.</p>

Intrahepatic biliary cystadenoma: experience with 10 consecutive cases at a single center / 南方医科大学学报

<p><b>OBJECTIVE</b>To summarize the clinical experience with diagnosis and treatment of intrahepatic biliary cystadenoma (IBCA).</p><p><b>METHODS</b>We retrospectively analyzed the data of 10 consecutive IBCA cases treated in our department in light of the characteristics of the epidemiology, radiology, lab tests, pathology and prognostic.</p><p><b>RESULTS</b>The patients are all female with an average age of 48.9 (16-73) years. The number of asymptomatic, slightly symptomatic and severe symptomatic patients was 4, 4 and 2, respectively. Radiological examination showed segmented cystic lesions in all the cases with an average diameter is 13.3∓4.9 cm. The incidence of segmentation, papillary or nodular hyperplasia, and calcification within the lesions was 90%, 60% and 20%, respectively. Macroscopic examination of the specimen showed compartmentation in the lesions, and microscopically, the lesions all showed lining of cubic or columnar epithelium on the inner wall with ovary-like or fibrous stroma. Complete resection of the tumor was achieved in 8 cases and partial resection was performed in 2 cases. The patients were followed up for a mean of 55.3 (12-164) months, and none of the patients with complete tumor resection showed recurrence, while both of the two patients with partial resection had postoperative recurrence.</p><p><b>CONCLUSION</b>IBCA is a rare cystic lesion occurring primarily in middle-aged women. The preoperative diagnosis of this disease relies primarily on radiological evidences, and a complete resection of IBCA may prolong the patient survival.</p>

Recombinant adenovirus with human indoleamine-2,3-dioxygenase and hepatitis B virus preS was constructed and expressed in HepG2 cells / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Indoleamine-2,3-dioxygenase (IDO) is proven to suppress hepatitis B virus (HBV) specific immune response and depletion of IDO may be a useful approach for HBV therapy. To test this concept, we constructed recombinant adenovirus with human IDO and HBV preS, which would form the basis for future in vivo experiments.</p><p><b>METHODS</b>The fragment of human IDO and HBV preS cDNA were subcloned into multiple cloning sites in an adenoviral vector system containing two cytomegalovirus (CMV) promoters. Recombination was conducted in the Escherichia coli BJ5183. The recombinant adenovirus containing hIDO gene and HBVpreS gene was packaged and amplified in 293 cells. Integration was confirmed by polymerase chain reaction as well as the quantification of viral titers. HepG2 cells were infected with the recombinant adenovirus and mRNA and protein specific for hIDO and HBVpreS was detected by RT-PCR and Western blotting respectively.</p><p><b>RESULTS</b>The recombinant adenovirus was produced successfully. Its titer was 2.5 × 10(9) efu/ml. IDO and HBVpreS mRNA as well as the encoded proteins could be found in transfected HepG2 cells, but not in control HepG2 cells.</p><p><b>CONCLUSION</b>The transfer of hIDO-HBVpreS with double-promoter adenoviral vector was efficient. The recombinant adenovirus with hIDO and HBV preS would provide the experimental basis for future studies.</p>

Diagnosis and treatment of fungal infection after liver transplantation / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Liver transplantation is the most effective treatment for end-stage liver diseases; however, infections after transplantation can seriously affect the patient's health. The aim of this research was to investigate the diagnosis and treatment of fungal infection following liver transplantation.</p><p><b>METHODS</b>Clinical data for 232 liver transplant patients at risk of fungal infection were examined for the presence of fungus in the blood, fluid, sputum, urine and stools of patients and by chest or abdominal CT scans. Patients diagnosed with a fungal infection were treated with Fluconazole or, if this was not effective, Voriconazole or Amphotericin B. Immunosuppressive therapy was also reviewed.</p><p><b>RESULTS</b>Thirty-seven of 232 (15.9%) patients were diagnosed with a fungal infection, which occurred 4 to 34 days post-transplantation. Candida infections were diagnosed in 23 cases (62.2%) and Aspergillus infections in 12 cases (32.4%). Twenty-one cases were effectively treated with Fluconazole, 11 cases with Voriconazole, and two cases with Amphotericin B; however, three cases were not effectively treated with any of the antifungal agents. Overall, treatment was effective in 91.9% of patients.</p><p><b>CONCLUSIONS</b>Fungal infection has a significant influence on survival rate after liver transplantation. Imaging studies, and pathogenic and biopsy examinations can diagnose fungal infections, which can be effectively treated with antifungal agents such as Fluconazole, Voriconazole or Amphotericin B.</p>

Clinical application of precise liver resection techniques in patients with complicated liver space-occupying lesions / 中华外科杂志

<p><b>OBJECTIVE</b>To evaluate the early results of precise liver resection.</p><p><b>METHODS</b>Between May 2006 and June 2009, 65 patients with complicated liver space-occupying lesions were included in the study. Fifty-one patients underwent curative liver resection. Liver resections performed included 16 trisectionectomies, 11 hemihepatectomy, 5 meso hepatectomies, 3 combined segmentectomies, 5 caudate lobectomies and 11 irregular local resections.</p><p><b>RESULTS</b>Patients undergoing resection had no mortality with a major morbidity of 9.8%. Nineteen vascular repairs and reconstructions were patent at last follow-up. The postoperative 1-year survival rate was 100% in 10 patients with benign lesions and 92.7% in 41 patients with malignant tumors. The 1-year survival rate was zero in patients with malignant tumors, who underwent no liver resection.</p><p><b>CONCLUSIONS</b>Precise liver resection, as an aggressive surgical approach, offers hope for these patients, who would otherwise have a dismal prognosis.</p>