Fabrication of 3D printed PCL/PEG artificial bile ducts as supportive scaffolds to promote regeneration of extrahepatic bile ducts in a canine biliary defect model.

In this study, a 3D porous poly(ε-caprolactone)/polyethylene glycol (PCL/PEG) composite artificial tubular bile duct was fabricated for extrahepatic bile duct regeneration. PCL/PEG composite scaffolds were fabricated by 3D printing, and the molecular structure, mechanical properties, thermal properties, morphology, and in vitro biocompatibility were characterized for further application as artificial bile ducts. A bile duct defect model was established in beagle dogs for in vivo implantation. The results demonstrated that the implanted PE1 ABD, serving as a supportive scaffold, effectively stimulated the regeneration of a new bile duct comprising CK19-positive and CK7-positive epithelial cells within 30 days. Remarkably, after 8 months, the newly formed bile duct exhibited an epithelial layer resembling the normal structure. Furthermore, the study revealed collagen deposition, biliary muscular formation, and the involvement of microvessels and fibroblasts in the regenerative process. In contrast, the anastomotic area without ABD implantation displayed only partial restoration of the epithelial layer, accompanied by fibroblast proliferation and subsequent bile duct fibrosis. These findings underscore the limited inherent repair capacity of the bile duct and underscore the beneficial role of the PE1 ABD artificial tubular bile duct in promoting biliary regeneration.

Advances in the DNA Nanotechnology for the Cancer Biomarkers Analysis: Attributes and Applications.

The most commonly used clinical methods are enzyme-linked immunosorbent assay (ELISA) and quantitative PCR (qPCR) in which ELISA was applied for the detection of protein biomarkers and qPCR was especially applied for nucleic acid biomarker analysis. Although these constructed methods have been applied in wide range, they also showed some inherent shortcomings such as low sensitivity, large sample volume and complex operations. At present, many methods have been successfully constructed on the basis of DNA nanotechnology with the merits of high accuracy, rapid and simple operation for cancer biomarkers assay. In this review, we summarized the bioassay strategies based on DNA nanotechnology from the perspective of the analytical attributes for the first time and discussed and the feasibility of the reported strategies for clinical application in the future.

Predictive factors of early recurrence after R0 resection of hilar cholangiocarcinoma: A single institution experience in China.

Prediction of early postoperative recurrence is of great significance for follow-up treatment. However, there are few studies available that focus on high-risk factors of early postoperative recurrence or even the definition the exact time of early recurrence for hilar cholangiocarcinoma. Thus, we aimed to examine the optimal cut-off value for defining the early in patients with R0 resection of hilar cholangiocarcinoma and to investigate prognostic factors associated with early recurrence. Two hundred and fifty-eight patients with R0 resection of hilar cholangiocarcinoma between 2000 and 2015 were included. The minimum P value approach was used to define the optimal cut-off of early recurrence. The prognostic factors associated with early recurrence were investigated. The optimal cut-off value for dividing patients into early and non-early recurrence groups after R0 resection of hilar cholangiocarcinoma was 12 months. Sixty-two patients were recorded as early recurrence, and the remaining 196 patients were labeled as non-early recurrence. Multivariate logistic regression analysis indicated lymph node metastasis (OR = 2.756, 95% CI 1.409-5.393; P = 0.003), poor differentiation (OR = 1.653; 95% CI 1.040-2.632; P = 0.034), increased postoperative CA 19-9 levels (OR = 1.965, 95% CI 1.282-3.013; P = 0.002), neutrophil-to-lymphocyte ratio > 3.41 (OR = 5.125, 95% CI 2.419-10.857; P < 0.001) and age > 60 years (OR = 2.018, 95% CI 1.032-3.947; P = 0.040) were independent determinants of early and non-early recurrence. Poor differentiation (HR = 2.609, 95% CI 1.600-4.252; P < 0.001), Bismuth classification type III/IV (HR = 2.510, 95% CI 1.298-4.852; P = 0.006) and perineural invasion (HR=2.380, 95% CI 1.271-4.457; P = 0.007) were independent factors of overall survival in the subgroup of patients who developed early recurrence. The optimal cut-off value for dividing early recurrence after R0 resection of hilar cholangiocarcinoma was 12 months. Tumor differentiation, Bismuth classification, and perineural invasion were independent factors of overall survival in the subgroup of patients with early recurrence. Patients with risk factors should be monitored closely after curative surgery.

Clinical Value of Inflammation-Based Prognostic Scores to Predict the Resectability of Hyperbilirubinemia Patients with Potentially Resectable Hilar Cholangiocarcinoma.

BACKGROUND: We aimed to examine whether inflammation-based prognostic scores could predict tumor resectability in a cohort of hilar cholangiocarcinoma patients with preoperative hyperbilirubinemia. We also sought to investigate the prognostic factors associated with overall survival in the subgroup of patients with an R0 resection. METHODS: A total of 173 patients with potentially resectable hilar cholangiocarcinoma, as judged by radiological examinations, were included. The potential relationship of the Glasgow prognostic score (GPS), modified GPS, platelet lymphocyte ratio (PLR), neutrophil lymphocyte ratio (NLR), prognostic nutritional index (PNI), and prognostic index (PI) with tumor resectability were investigated using univariate and multivariate analysis. RESULTS: Among the 173 patients, 134 had R0 resection margins. Univariate analysis identified that patients with PLR ≥ 150, NLR ≥ 3, PNI ≥ 45, GPS (0.1/2), modified GPS (0.1/2), preoperative CA 125 > 35 U/mL, and a tumor size ≥ 3 cm were more likely to have unresectable tumors. Multivariate analysis indicated that tumor size ≥ 3 cm (OR = 2.422, 95% CI: 1.053-5.573; P = 0.037), PLR ≥ 150 (OR = 3.324, 95% CI: 1.143-9.667; P = 0.027), preoperative CA 125 > 35 U/mL (OR = 3.184, 95% CI: 1.316-7.704; P = 0.010), and GPS (0.1/2) (OR = 2.440, 95% CI: 1.450-4.107; P = 0.001) were independent factors associated with tumor resectability. In selected patients with an R0 resection in this cohort, nodal status (P = 0.010) and tumor differentiation (P = 0.025) were predictive of poor survival outcome. CONCLUSION: Patients with higher GPS, CA 125, and PLR levels, and a larger tumor size, tend to have unresectable tumors even if they were judged as potentially resectable using preoperative radiological examinations.

Effectiveness of additional resection of the invasive cancer-positive proximal bile duct margin in cases of hilar cholangiocarcinoma.

BACKGROUND: The survival benefits of additional resection of the positive proximal ductal margin (PM) in hilar cholangiocarcinoma (HCCA) remains controversial. This retrospective study investigated the effectiveness of additional resection of the invasive cancer PM under different levels of preoperative carbohydrate antigen 19-9 (CA19-9). METHODS: Patients who underwent hepatectomy for HCCA from 2000 to 2017 were analyzed. Surgical variables, resection margin status, length of the PM (LPM), prognostic factors, and survival were evaluated. RESULTS: A total of 228 patients were enrolled: 175 PM(-) without additional resection patients (group A), 21 PM(-) after additional resection (group B), 16 PM(+) without additional resection (group C), and 16 PM(+) after additional resection (group D). The median survival of group B (20.99 months) was similar to that of group A (23.00 months; P=0.16), and both were significantly better than those of group C (11.60 months) and D (9.50 months), especially when preoperative CA19-9>150 U/mL (P<0.05). The survival of patients with an LPM >10 mm was significantly better compared with those with an LPM ≤10 mm, especially when preoperative CA19-9 was >150 U/mL (P<0.05). Only in the LPM >10 mm group, the survival of group B was comparable with that of group A (P>0.05). CONCLUSIONS: HCCA patients could get a survival benefit from a negative PM resulting from additional resection. Survival could be comparable with that of negative PM without additional resection among HCCA patients. An LPM >10 mm is possibly more associated with better survival compared with whether additional resection of the positive PM is performed under different levels of preoperative CA19-9.

Alveolar echinococcosis in the head of pancreas: A case report.

RATIONALE: Pancreatic alveolar echinococcosis (AE) is an exceptionally rare disease; no more than 10 cases have been published to date. It is characterized as extensive local tissue infringement and destruction; thus, extended surgical resection, such as duodenopancreatectomy, is often needed to obtain a negative resection margin so as to improve the long-term outcome and prognosis. PATIENT CONCERNS: A middle-aged Tibetan man was admitted due to a 16-year history of recurrent pain in the right upper abdomen. Magnetic resonance imaging scan showed a cystic lesion in the VI segment of his liver and several cystic lesions in the head of pancreas. DIAGNOSES: Pancreatic AE. INTERVENTIONS: The patient adopted a preserved surgery of partial cystectomy and completely removing the content of the cyst and then soaking by hypertonic saline combined with adjuvant medical therapy of albendazole. OUTCOMES: The patient was monitored on a regular basis at the outpatient department; the patient is still alive and has already survived 8 years till now. LESSONS: A preserved surgery combined with adjuvant medical therapy of albendazole can also contribute to a good survival outcome for AE located at the head of pancreas.

You cannot miss it: Pancreatic mucoepidermoid carcinoma: A case report and literature review.

RATIONALE: Pancreatic mucoepidermoid carcinoma (MEC) is a rare disease with no more than 10 cases reported in literature. The prognosis is poor and few patients can survival more than 1 year. PATIENT CONCERNS: We presented a case of patient manifested as left upper abdominal pain. Computed tomography demonstrated a low-density shadow measuring 2.1 × 2.4 cm situated at the transition area of neck and body of the pancreas with obscure boundary and irregular enhancement. The preoperative symptoms and imaging features were unspecific. DIAGNOSES: Pancreatic MEC. INTERVENTIONS: Curative surgery of distal pancreatectomy was conducted. Postoperatively, the patient subsequently underwent 8 cycles of chemotherapy using cisplatin (25 mg/m) on day 1 to day 3; and gemcitabine (1000 mg/m) on day 1 and day 8, repeated every 21 days. OUTCOMES: The patient was monitored on a regular basis at our outpatient department and survived 23 months after surgery. LESSONS: Preoperative diagnosis of pancreatic MEC is difficult. Patients with pancreatic MEC may have a survival benefit from the multimodal treatment of curative surgery combined with chemotherapy.

Hepatic Artery Resection for Bismuth Type III and IV Hilar Cholangiocarcinoma: Is Reconstruction Always Required?

OBJECTIVE: The objective of the study is to examine the feasibility of hepatic artery resection (HAR) without subsequent reconstruction (RCS) in specified patients of Bismuth type III and IV hilar cholangiocarcinoma. METHODS: We retrospectively reviewed 63 patients who underwent hepatic artery resection for Bismuth type III and IV hilar cholangiocarcinoma. These patients were subsequently enrolled into two groups based on whether the artery reconstruction was conducted. Postoperative morbidity and mortality, and long-term survival outcome were compared between the two groups. RESULTS: There were 29 patients in HAR group and 34 patients in the HAR + RCS group. Patients with hepatic artery reconstruction tended to have longer operative time (545.6 ± 143.1 min vs. 656.3 ± 192.8 min; P = 0.013) and smaller tumor size (3.0 ± 1.1 cm vs. 2.5 ± 0.9 cm; P = 0.036). The R0 resection margin was comparable between the HAR group and HAR + RCS group (86.2 vs. 85.3%; P > 0.05). Twelve patients (41.4%) with 24 complications in HAR group and 13 patients (38.2%) with 25 complications in HAR + RCS group were recorded (P = 0.799). The postoperative hepatic failure rate (13.8 vs. 5.9%) and postoperative mortality rate (3.4% vs. 2.9%) were also comparable between the two groups. In the HAR group, the overall 1-, 3-, and 5-year survival rates were 72, 41, and 19%, respectively; while in the HAR + RCS group, the overall 1-, 3-, and 5-year survival rates were 79, 45, and 25%, respectively (P = 0.928). CONCLUSIONS: Hepatic artery resection without reconstruction is also a safe and feasible surgical procedure for highly selected cases of Bismuth type III and IV hilar cholangiocarcinoma.

Relationship of tumor size with pathological and prognostic factors for hilar cholangiocarcinoma.

OBJECTIVE: To determine the correlation of different tumor-size cutoffs with prognostic factors and survival outcomes to provide a reference for the modification of the T-stage classification in the DeOliveira staging system for hilar cholangiocarcinoma (HCCA). MATERIALS AND METHODS: We retrospectively analyzed 216 patients who underwent curative surgery for HCCA (mean tumor diameter, 2.8 cm) between 2000 and 2013. Univariate and multivariate logistic regression were used to assess the correlation of tumor-size cutoffs with various factors. RESULTS: Tumor differentiation (odds ratio [OR]: 1.649, 95% confidence interval [CI]: 1.065-2.555, P = 0.025), node status (OR: 1.971, 95% CI: 1.060-3.664, P = 0.032), resection margin (OR: 2.465, 95% CI: 1.024-5.937, P = 0.044), and hepatectomy (OR: 2.373, 95% CI: 1.226-4.593, P = 0.01) were independently correlated with the 2-cm cutoff, while tumor differentiation (OR: 1.755, 95% CI: 1.062-2.091, P = 0.028), node status (OR: 2.166, 95% CI: 1.054-4.452, P = 0.035), and tumor margin (OR: 2.539, 95% CI: 1.089-5.919, P = 0.031) were independently associated with the 3-cm cutoff. CONCLUSIONS: The 2-cm and 3-cm cutoffs were strongly correlated with resection margin, node status, tumor differentiation and survival. The 2-cm cutoff may be added to the DeOliveira staging system.

Elevated red blood cell distribution width predicts poor prognosis in hilar cholangiocarcinoma.

BACKGROUND: Although the red blood cell distribution width (RDW) has been reported as a reliable predictor of prognosis in several types of cancer, the prognostic value of RDW in hilar cholangiocarcinoma (HC) has not been studied. METHODS: A retrospective analysis of 292 consecutively recruited HC patients undergoing radical resection was conducted. The optimal cutoff value of RDW was determined by the receiver operating characteristic curve (ROC). Survival analysis by the Kaplan-Meier method, the difference between the clinico-pathologic variables and survival were evaluated by log-rank analysis. Multivariate analysis identified independent prognostic risk factors of overall survival (OS). RESULTS: ROC analysis suggested that the optimal cutoff value for the RDW was 14.95. Linear correlation analysis revealed that RDW is associated with white blood cell count (P = 0.007), neutrophil-to-lymphocyte ratio (P = 0.02), and hemoglobin (P < 0.001), albumin (P < 0.001). In a multivariate analysis, the RDW was an independent prognostic factor for OS (HR = 1.755, 95% CI 1.311-2.349, P < 0.001). CONCLUSIONS: Elevated RDW may be regarded as an indicator of systemic inflammatory response which might facilitate HC growth and metastasis. Current evidence suggests that RDW may have clinical significance in predicting OS after surgery in HC patients.

Coexisting cancers: a mixture of neuroendocrine carcinoma and adenocarcinoma in the gallbladder: A case report.

BACKGROUND: Neuroendocrine carcinoma is rare with a proportion of less than 2% in gallbladder malignancies, cases of gallbladder neuroendocrine cell carcinoma coexisting with adenocarcinoma are exceptionally rare, and the prognosis is dismal. METHODS: Herein, we presented an unusual case of poorly differentiated gallbladder neuroendocrine cell carcinoma coexisting with poorly differentiated adenocarcinoma who survived 20 months after the multimodal treatment (MT) of extended surgery and postoperative chemotherapy. RESULTS: Our result indicated that for advanced gallbladder neuroendocrine cell carcinoma coexisting with adenocarcinoma, MT including extended surgical approach combined with postoperative chemotherapy may contribute to a relatively good survival outcome. CONCLUSION: MT may contribute to a relatively good survival outcome for advanced gallbladder neuroendocrine cell carcinoma coexisting with gallbladder adenocarcinoma.

Negative short-term impact of intraoperative biliary lavage in patients with hepatolithiasis.

AIM: To evaluate short-term outcomes following intraoperative biliary lavage for hepatolithiasis. METHODS: A total of 932 patients who were admitted to the West China Medical Center of Sichuan University between January 2010 and January 2014 and underwent bile duct exploration and lithotomy were retrospectively included in our study. The patients were divided into the lavage group and the control group. Related pre-, intra-, and postoperative factors were recorded, analyzed, and compared between the two groups in order to verify the effects of biliary lavage on the short-term outcome of patients with hepatolithiasis. RESULTS: Amongst the patients who were included, 678 patients with hepatolithiasis were included in the lavage group, and the other 254 patients were enrolled in the control group. Data analyses revealed that preoperative baseline and related intraoperative variables were not significantly different. However, patients who underwent intraoperative biliary lavage had prolonged postoperative hospital stays (6.67 d vs 7.82 d, P = 0.024), higher hospitalization fees (RMB 28437.1 vs RMB 32264.2, P = 0.043), higher positive rates of bacterial cultures from blood (13.3% vs 25.8%, P = 0.001) and bile (23.6% vs 40.7%, P = 0.001) samples, and increased usage of advanced antibiotics (26.3% vs 38.2%, P = 0.001). In addition, in the lavage group, more patients had fever (> 37.5 °C, 81.4% vs 91.1%, P = 0.001) and hyperthermia (> 38.5°C, 39.7% vs 54.9%, P = 0.001), and higher white blood cell counts within 7 d after the operation compared to the control group. CONCLUSION: Intraoperative biliary lavage might increase the risk of postoperative infection, while not significantly increasing gallstone removal rate.

Repair of a common bile duct defect with a decellularized ureteral graft.

AIM: To evaluate the feasibility of repairing a common bile duct defect with a decellularized ureteral graft in a porcine model. METHODS: Eighteen pigs were randomly divided into three groups. An approximately 1 cm segment of the common bile duct was excised from all the pigs. The defect was repaired using a 2 cm long decellularized ureteral graft over a T-tube (T-tube group, n = 6) or a silicone stent (stent group, n = 6). Six pigs underwent bile duct reconstruction with a graft alone (stentless group). The surviving animals were euthanized at 3 mo. Specimens of the common bile ducts were obtained for histological analysis. RESULTS: The animals in the T-tube and stent groups survived until sacrifice. The blood test results were normal in both groups. The histology results showed a biliary epithelial layer covering the neo-bile duct. In contrast, all the animals in the stentless group died due to biliary peritonitis and cholangitis within two months post-surgery. Neither biliary epithelial cells nor accessory glands were observed at the graft sites in the stentless group. CONCLUSION: Repair of a common bile duct defect with a decellularized ureteral graft appears to be feasible. A T-tube or intraluminal stent was necessary to reduce postoperative complications.

Prognostic Significance of Sarcomatous Change in Patients with Hepatocellular Carcinoma After Surgical Resection.

BACKGROUND: Hepatocellular carcinoma (HCC) with sarcomatous change (SC) is a rare malignancy associated with high aggressiveness and poor prognosis; however, its prognostic significance remains unclear. METHODS: From January 1994 to April 2012, surgically resected HCCs with SC (n = 52) at West China Hospital were retrospectively reviewed. HCC with SC was defined as the concomitant presence of the sarcomatous component occupying at least 10 % (but not predominantly) of the HCC-bearing tissue. To validate its prognostic significance, we compared the clinicopathological features and survival rates of these patients with a cohort of 214 randomly selected ordinary HCC patients during the same period. RESULTS: The clinicopathological characteristics of HCC with SC were similar to those of ordinary HCC, with the exception of capsule formation, adjacent organ invasion, lymph node metastasis, and TNM staging. A total of 45 (86.5 %) HCC patients with SC experienced a recurrence, with a median time to recurrence of 6.0 months. Overall survival (OS) rates in the sarcomatous HCC group at 1, 2, and 3 years were 55.8, 25, and 17.3 %, respectively, which were significantly lower than those in the ordinary HCC group (p < 0.001). On multivariable analysis, macrovascular invasion, satellite nodules, and R1/R2 resection were identified as independent risk factors for shorter disease-free survival and OS. CONCLUSIONS: The presence of SC in HCC was uncommon, and was associated with much poorer prognosis than ordinary HCC. Radical resection with negative margin is essential for improving the prognosis. Future prospective studies are warranted to determine if recurrent patients can benefit from postoperative adjuvant therapies.