Estrogen Deficiency Aggravates Fluoride-Induced Liver Damage and Lipid Metabolism Disorder in Rats.

Estrogen exerts essential role in liver metabolism, and its deficiency is frequently accompanied by a series of metabolic disorder diseases. To investigate the role of estrogen deficiency in fluorine ions (F-) induced liver injury, the ovariectomy (OVX) rat models were performed by surgically removing the ovaries, and the rats from OVX and non-OVX models were exposed to differential dose of F- (0, 25, 50 and 100 mg/L) in drinking water for 90 days. The liver morphological structure was evaluated by hematoxylin-eosin staining. Proliferation ability of hepatocytes was evaluated by 5-bromo-2-deoxyuridine (BrdU) assay. And distribution of lipid droplets in liver tissue was observed via oil red O staining. In addition, the liver function and lipid metabolism parameters in serum were detected by commercial kits. Results showed that F- induced hepatocytes morphological damage and inhibited the proliferation ability of hepatocytes; estrogen deficiency exacerbated these changes. The deposition of lipid droplets in the liver tissue was multiplicative with increased F- dose, especially after estrogen deficiency. In addition, F- exposure increased (P < 0.05 or P < 0.01) serum aminotransferase (ALT), aminotransferase (AST), alkaline phosphatase (ALP), and γ-glutamyl transpeptidase (γ-GT) activities and total bilirubin (T-bil) level; meanwhile, serum triglyceride (TG) and cholesterol (TC) levels were also elevated (P < 0.05 or P < 0.01). F--induced liver function and lipid metabolism indexes were further increased (P < 0.05 or P < 0.01) in the state of estrogen deficiency. In conclusion, estrogen deficiency aggravated F--induced liver damage and lipid metabolism disorder.

Combined targeted therapy and immunotherapy for cancer treatment.

Although targeted therapies and immunotherapies have been effective against several malignancies, the respective monotherapies are limited by low and/or short-term responses. Specific inhibitors of oncogenic signaling pathways and tumor-associated angiogenesis can activate the anti-tumor immune responses by increasing tumor antigen presentation or intratumor T cell infiltration. Additional insights into the effects and mechanisms of targeted therapies on the induction of anti-tumor immunity will facilitate development of rational and effective combination strategies that synergize rapid tumor regression and durable response. In this review, we have summarized the recent combinations of targeted therapies and immunotherapies, along with the associated clinical challenges.

Prediction of postoperative pancreatic fistula using a nomogram based on the updated definition.

PURPOSE: The International Study Group on Pancreatic Fistula's definition of postoperative pancreatic fistula (POPF) has recently been updated. This study aimed to identify risk factors for POPF in patients having pancreaticoduodenectomy (PD) and to generate a nomogram to predict POPF. METHODS: Data on 298 patients who underwent PD from March 2012 to October 2017 was retrospectively reviewed and POPF statuses were redefined. A nomogram was constructed using data from 220 patients and validated using the remaining 78 patients. Independent risk factors for POPF were identified using univariate and multivariate analyses. A predictive nomogram was established based on the independent risk factors and was compared with existing models. RESULTS: Texture of the pancreas, size of the main pancreatic duct, portal vein invasion, and definitive pathology were the identified risk factors. The nomogram had a C-index of 0.793 and was internally validated. The nomogram performed better (C-index of 0.816) than the other most cited models (C-indexes of 0.728 and 0.735) in the validation cohort. In addition, the nomogram can assign patients into low- (less than 10%), intermediate- (10% to 30%), and high-risk (equal or higher than 30%) groups to facilitate personalized management. CONCLUSION: The nomogram accurately predicted POPF in patients having PD.

Development of a Novel Multiparametric MRI Radiomic Nomogram for Preoperative Evaluation of Early Recurrence in Resectable Pancreatic Cancer.

BACKGROUND: In pancreatic cancer, methods to predict early recurrence (ER) and identify patients at increased risk of relapse are urgently required. PURPOSE: To develop a radiomic nomogram based on MR radiomics to stratify patients preoperatively and potentially improve clinical practice. STUDY TYPE: Retrospective. POPULATION: We enrolled 303 patients from two medical centers. Patients with a disease-free survival ≤12 months were assigned as the ER group (n = 130). Patients from the first medical center were divided into a training cohort (n = 123) and an internal validation cohort (n = 54). Patients from the second medical center were used as the external independent validation cohort (n = 126). FIELD STRENGTH/SEQUENCE: 3.0T axial T1 -weighted (T1 -w), T2 -weighted (T2 -w), contrast-enhanced T1 -weighted (CET1 -w). ASSESSMENT: ER was confirmed via imaging studies as MRI or CT. Risk factors, including clinical stage, CA19-9, and radiomic-related features of ER were assessed. In addition, to determine the intra- and interobserver reproducibility of radiomic features extraction, the intra- and interclass correlation coefficients (ICC) were calculated. STATISTICAL TESTS: The area under the receiver-operator characteristic (ROC) curve (AUC) was used to evaluate the predictive accuracy of the radiomic signature in both the training and test groups. The results of decision curve analysis (DCA) indicated that the radiomic nomogram achieved the most net benefit. RESULTS: The AUC values of ER evaluation for the radiomics signature were 0.80 (training cohort), 0.81 (internal validation cohort), and 0.78 (external validation cohort). Multivariate logistic analysis identified the radiomic signature, CA19-9 level, and clinical stage as independent parameters of ER. A radiomic nomogram was then developed incorporating the CA19-9 level and clinical stage. The AUC values for ER risk evaluation using the radiomic nomogram were 0.87 (training cohort), 0.88 (internal validation cohort), and 0.85 (external validation cohort). DATA CONCLUSION: The radiomic nomogram can effectively evaluate ER risks in patients with resectable pancreatic cancer preoperatively, which could potentially improve treatment strategies and facilitate personalized therapy in pancreatic cancer. LEVEL OF EVIDENCE: 4 Technical Efficacy: Stage 4 J. Magn. Reson. Imaging 2020;52:231-245.

The efficacy and toxicity of chemotherapy in the elderly with advanced pancreatic cancer.

OBJECTIVES: FOLFIRINOX (FFX) or abraxane plus gemcitabine (AG)-based chemotherapy is used widely as firstline treatment for patients with pancreatic cancer. However, their use in the elderly is discouraged because of adverse events. More clinical data about the therapeutic response and tolerability to FFX or AG in elderly patents (over 70 years old) are required. METHODS: Patients with advanced pancreatic cancer (n = 203; 131 metastatic pancreatic cancer patients (MPC) and 72 locally advanced pancreatic cancer patients (LAPC)) were treated using modified-FFX (mFFX) or AG and mFFX sequentially. The patients were grouped according to their age, patients below 70 years old and patients above 70 years old. The objective response rate (ORR), disease control rate (DCR), progression free survival (PFS), overall survival (OS) and adverse events were compared between the groups. RESULTS: The ORRs in the elderly and in patients below 70 were similar (30.0% versus 32.3%). The median OS and PFS were also similar between the groups (mOS 13.3 m vs 12.7 m, p = 0.729, HR 0.874 (95% CI 0.5310 to 1.438); mPFS mPFS 10.6 m vs 10.3 m, p = 0.363, HR 0.800 (95% CI 0.4954 to 1.293)). However, the elderly patients suffered a higher incidence of severe adverse events (50% vs. 28.3%). CONCLUSIONS: These data could provide guidance for chemotherapy use in elderly patients with advanced pancreatic cancer. Age did not affect treatment outcome; however, supportive treatment is very important for elderly patients receiving chemotherapy.

A nomogram for prediction of posthepatectomy liver failure in patients with hepatocellular carcinoma: A retrospective study.

To generate a nomogram to predict posthepatectomy liver failure (PHLF), we attempted to elucidate salient risk factors in patients with hepatocellular carcinoma (HCC).We performed a retrospective review of 665 patients with HCC who received hepatectomy in 2 academic institutions in China. Independent risk factors for PHLF were identified from putative demographic, intrinsic, biochemical, surgery-related, and volumetric data. A predictive nomogram was formulated based on relevant risk factors, and we compared this with existing models.We identified clinical signs of portal hypertension (P = .023), serum total bilirubin (P = .001), serum creatinine (P = .039), and intraoperative hemorrhage (P = .015) as being important risk factors in predicting PHLF. The nomogram had a C-index of 0.906 for the externally validated data. The nomogram displayed better predictive value than 2 of the other most cited models (C-indices of 0.641 and 0.616, respectively) in the current cohort. Additionally, we were able to patients into low- (<10%), intermediate- (10-30%), and high-risk (≥30%) groups based on the nomogram. This allows us to facilitate person-specific management.Here, we constructed a simple nomogram for prediction of PHLF in patients with HCC weighted by independent risk factors. Further prospective studies are required to confirm the predictive ability of our nomogram.

Predicting surgical site infections using a novel nomogram in patients with hepatocelluar carcinoma undergoing hepatectomy.

BACKGROUND: Surgical site infections (SSI) remain a major cause of morbidity after hepatectomy for hepatocellular carcinoma (HCC). AIM: To identify the risk factors associated with SSI, and develop a nomogram to predict SSI among patients undergoing hepatectomy. METHODS: We retrospectively reviewed the data of patients diagnosed with HCC undergoing hepatectomy at two academic institutions in China, and evaluated the occurrence of SSI. Independent risk factors for SSI were identified using univariate and multivariate analyses. Based on these independent risk factors, a nomogram was established using the data of patients in the first institution, and was validated using data from an external independent cohort from the second institution. RESULTS: The nomogram was established using data from 309 patients, whereas the validation cohort used data from 331 patients. The operation duration, serum albumin level, repeat hepatectomy, and ASA score were identified as independent risk factors. The concordance index (C-index) of the nomogram for SSI prediction in the training cohort was 0.86; this nomogram also performed well in the external validation cohort, with a C-index of 0.84. Accordingly, we stratified patients into three groups, with a distinct risk range based on the nomogram prediction, to guide clinical practice. CONCLUSION: Our novel nomogram offers good preoperative prediction for SSIs in patients undergoing hepatectomy.

The First Report of Laparoscopic Pancreaticoduodenectomy for Primary Duodenal Carcinoma in a Patient With Situs Inversus Totalis: Report of a Rare Case.

BACKGROUND: Situs inversus (SI) is a rare congenital anomaly characterized by the transposition of thoracic and abdominal viscera. Laparoscopic pancreaticoduodenectomy (LPD) is increasingly used in patients with periampullar and pancreatic carcinomas. For patients with SI, LPD can be more complicated because of reversed anatomy and possible other associated anomalies that have not been expected before surgery. CASE PRESENTATION: A female patient with SI totalis presented with inappetence, vomiting, and weight loss for 2 months. Imaging modalities and angiography revealed a mass in the periampullary region without obvious vascular abnormalities. The mass was successfully resected via LPD based on an elaborate preoperative plan. The surgical pathology report demonstrated adenocarcinoma of the duodenal papilla. The patient has been followed up for 4 months and no tumor recurrence or long-term complications were observed. CONCLUSION: LPD is technically difficult but feasible in patients with SI.

Preoperative prediction of peripancreatic vein invasion by pancreatic head cancer.

BACKGROUND: Pancreatic adenocarcinoma is often diagnosed at an advanced stage when adjacent vascular invasion is present. Accurate evaluation of presence of vascular invasion can help guide therapy. The aim of this study was to construct a nomogram for preoperative prediction of peripancreatic vein invasion in patients with pancreatic head cancer. STUDY DESIGN: Data of patients with carcinoma head of pancreas and suspected peripancreatic invasion (n = 247) who underwent pancreatic resection with venous reconstruction between January 2012 and January 2017 at four academic institutions were retrospectively analyzed. Univariate and multivariate analyses were used to identify independent risk factors for vein invasion from among demographic, biological, conditional host-related, and anatomical data. A predictive nomogram was constructed based on the identified independent risk factors. RESULTS: The nomogram was constructed using data from 181 patients while the validation cohort consisted of 66 patients. Length of tumor contact (P = 0.031), circumferential vein involvement (P = 0.048), and venous contour abnormalities (P = 0.001) were independent predictors of venous invasion. The C-index of the model in predicting venous invasion was 0.963 for the external validation cohort. Patients could be assigned into low- (< 50%), intermediate- (50-90%), and high-risk (> 90%) groups based on the nomogram to facilitate personalized management. CONCLUSIONS: Vein invasion by pancreatic head cancer is mainly associated with anatomical factors. The nomogram for prediction of vein invasion was found to be practicable.

Associating liver partition and portal vein ligation versus 2-stage hepatectomy: A meta-analysis.

BACKGROUND: The aim of this study was to conduct a meta-analysis comparing associating liver partition and portal vein ligation (ALPPS) with conventional 2-stage hepatectomy (TSH) in terms of clinical outcomes and to determine the feasibility and safety of ALPPS. METHODS: A comprehensive search strategy was adopted to search the PubMed, Embase, Cochrane Library, and China Biology Medicine disc databases for studies comparing ALPPS and TSH. The search was broadened by looking up the reference lists of the retrieved articles. A meta-analysis was performed using the statistical software RevMan (v 5.3; Cochrane Collaboration). RESULTS: A total of 7 studies involving 561 patients (ALPPS group, 136 patients; TSH group, 425 patients) were included in the present study, all of which were observational studies. Compared with TSH, ALPPS was associated with high completion rates of both stages [odds ratio (OR): 10.68, 95% confidence interval (95% CI): 3.26-34.97, P < .0001]. No significant differences were found in other outcomes such as complications of the first (OR: 4.04, 95% CI: 0.81-20.27, P = .09) and second surgical stage (OR: 1.59, 95% CI: 0.71-3.57, P = .26), liver failure (OR: 0.76, 95% CI: 0.29-1.98, P = .58) and the 90-day mortality rate (OR: 2.20, 95% CI: 1.00-4.84, P = .05). CONCLUSION: ALPPS is associated with lower noncompletion rate and had similar perioperative outcomes relative to TSH. However, only retrospective observational studies were included in this meta-analysis, which may have limited the strength of the evidence. High-quality, large-scale studies are required to further evaluate the outcomes of ALPPS.

The role of imaging in prediction of post-hepatectomy liver failure.

Post-hepatectomy liver failure (PHLF) is not only a leading cause of mortality but also a leading cause of life-threatening complications in patients undergoing liver resection. The ability to accurately detect the emergence of PHLF represents a crucially important step. Currently, PHLF can be predicted by a comprehensive evaluation of biological, clinical, and anatomical parameters. With the development of new technologies, imaging methods including elastography, diffusion-weighted magnetic resonance imaging, and gadolinium ethoxybenzyl diethylenetriaminepentaacetic acid-enhanced MRI play a more significant role in the pre-operative prediction and assessment of PHLF. In this review, we summarize the mainstream studies, with the aim of evaluating the role of imaging and improving the clinical value of existing scoring systems for predicting PHLF.

A preoperative nomogram predicts prognosis of up front resectable patients with pancreatic head cancer and suspected venous invasion.

BACKGROUND: Pancreatic head adenocarcinoma is commonly diagnosed at an advanced stage when adjacent vascular invasion is present. This study aimed to establish a preoperative prognostic nomogram for patients who underwent attempted curative resectional surgery for pancreatic head cancer with suspected peripancreatic venous invasion. METHODS: Data on all consecutive patients were retrospectively collected from 2012 to 2016 at four academic institutions. The demographic and radiological parameters were analyzed using univariate and multivariate Cox regression analyses. The final nomogram was established using the concordance Harrell's C-indices and calibration curves from data obtained in three institutions and validated in the cohort of patients coming from the fourth institution. RESULTS: The nomogram was constructed using data from 178 patients while the validation cohort consisted of 61 patients. Age, length of tumor contact, peripancreatic venous abnormalities and lymph node staging were independent factors of overall survival. The nomogram showed good probabilities of survival on calibration curves. The C-index of the model in predicting overall survival (OS) was 0.824 for the validation cohort. CONCLUSIONS: The nomogram accurately predicted OS in patients with pancreatic head cancer with suspected peripancreatic venous invasion after attempted curative pancreatic resectional surgery.

Modified-FOLFIRINOX in metastatic pancreatic cancer: A prospective study in Chinese population.

FOLFIRINOX chemotherapy has shown remarkable responses in patients with metastatic pancreatic cancer (MPC), and has significantly improved prognosis. However, FOLFIRINOX is currently not frequently applied in China because of its high incidence of adverse events, and there is no recognized optimization for this therapy in Chinese population. Modification of FOLFIRINOX may be better for its acceptance in China. In this study, we evaluated the efficacy and safety of modified-FOLFIRINOX in patients with MPC. A total of 62 MPC patients were treated with modified-FOLFIRINOX (no Fluorouracil bolus, 85% Oxaliplatin and 75% Irinotecan) between April 2014 and April 2017 in our institute. 40 of them were evaluated, with a response rate of 32.5% (13/40). The frequent grade 3/4 adverse events are neutropenia (29%) and alanine aminotransferase elevation (14.5%). No treatment-related death was observed. The median overall survival and median progression-free survival are 10.3 months and 7.0 months, respectively. In conclusion, modified-FOLFIRINOX had significantly improved tolerance with similar efficacy to FOLFIRINOX. These findings may provide evidence for the use of FOLFIRINOX in Chinese patients with MPC.

Compatibility of Schistosoma japonicum from the hilly region and Oncomelania hupensis hupensis from the marshland region within Anhui, China.

Schistosome japonicum remains one main public concern in China. This is exemplified in the hilly region in Anhui Province, where rodents have served as reservoirs for the parasite and no effective intervention could target such wild animals. The closer relationship between the hilly region and the near marshland induces the worry of spread of the hill parasite to the marshland region. Therefore, the level of snail-parasite compatibility between the hill parasite and snail populations from the Yangtze River valley was investigated. The results of this study demonstrated that both the hill (Shitai, Anhui) and the marshland (Wuxi, Jiangsu) strains of parasite were more infective to the marshland strains of snail (Zongyang and Hexian, Anhui) than to the hill strain of snail (Shitai, Anhui). When snails were individually exposed to one single miracidium, the longest prepatent period for cercarial development was observed in the combination of Shitai schistosome/Shitai snail. A nocturnal cercarial emergence pattern was observed for the hill parasite, either harbored in the hill or the marshland strain of snails. The results suggested a high compatibility between the marshland strains of snail and both the hill and the marshland strains of parasite. This would have practical implications. Moreover, the fact of the lower compatible relationship between the hill parasite and its local intermediate hosts warranted more studies.