Intraoperative radiotherapy vs concurrent chemoradiotherapy in the treatment of patients with locally advanced pancreatic cancer.

PURPOSE: The purpose of the multi-institutional retrospective study was to evaluate whether intraoperative radiotherapy (IORT) has advantages in the treatment of patients with locally advanced pancreatic cancer (LAPC) compared with concurrent chemoradiotherapy (CCRT). PATIENTS AND METHODS: A total of 103 patients with LAPC whom was treated with IORT (Arm A; n = 50) or CCRT (Arm B; n = 53) from 2015.6 to 2016.7 were retrospectively identified. Data on feasibility, toxicity, and overall survival (OS) were evaluated. RESULTS: Most factors of the two cohorts were similar. The severe adverse events (grade 3 and 4) patients in Arm B were higher than patients in Arm A (34% vs 0%). Disease progression was noted in 38 patients (76%) in Arm A and 37 patients (69.8%) in Arm B. The median survival of patients in Arm A and B were 15.3 months (95% CI, 13.0-17.6 months) and 13.8 months (95% CI, 11.0-16.6 months), respectively. The 1-year survival rate were 66.3% in Arm A (95% CI, 52.3%-80.2%) and 60.9% in Arm B (95% CI, 46.4%-75.4%). There was no significant difference in OS between patients treated with IORT and with CCRT (p = 0.458). CONCLUSION: Our results demonstrated that patients with LAPC treated with IORT showed fewer adverse events, less treatment time, and high feasibility compared to CCRT. Although, IORT has no advantages in survival and tumor control compared with CCRT.

Early plasma exchange for treating ricin toxicity in children after castor bean ingestion.

Plasma exchange (PE) for the treatment of ricin toxicity has not been previously reported. Here we describe the use of PE to treat children who experienced ricin toxicity after ingesting castor beans. Seven children (median age: 8.1 years) who consumed castor beans (median: 5 beans) were treated with PE. All had bradycardia and sinus arrhythmia, and most had experienced episodes of vomiting and/or diarrhea. PE settings were blood flow, 50-80 mL/min; PE rate, 600-800 mL/h; volume of exchange, 1440-1950 mL. Median time from ingestion to PE was 73 h. All clinical symptoms disappeared and vital signs rapidly returned to normal after PE; no severe organ dysfunction occurred. All children were discharged and recovered uneventfully. Concentrations of all serum biochemical parameters significantly decreased immediately after PE. Some, but not all, of these parameters were also significantly decreased at 48 and 72 h after PE compared with before PE. Our findings suggest that PE can be an effective early intervention in the treatment of ricin toxicity due to castor bean ingestion.

[Mutational analysis of MYO1E in Chinese children with familial steroid-resistant nephrotic syndrome].

OBJECTIVE: Steroid-resistant nephrotic syndrome (SRNS) with MYO1E mutations has been identified as autosomal recessive focal segmental glomerulosclerosis (FSGS). To date, only two homozygous mutations in the MYO1E gene were reported in three families with FSGS. This study aimed to examine mutations in the MYO1E gene in children with familial SRNS in the Han Chinese ethnic group. METHODS: Between 2005 and 2010, peripheral blood samples were collected from the probands, their siblings and parents of four families with autosomal recessive SRNS in the Han Chinese ethnic group. Four probands were studied from nine patients. The mutational analysis of MYO1E was performed by polymerase chain reaction and direct DNA sequencing. Fifty-nine healthy volunteers with normal urine analysis were included as controls. RESULTS: Twenty-five MYO1E variants in the prohands from 4 families with SRNS were identified in this study. Among them, 24 variants were found in NCBI dbSNP. One heterozygous mutation IVS21-85G>A was found in the prohand from Family D, whereas it was absent in 59 normal Chinese controls. No splice site change caused by IVS21-85G>A was reported by analysis with NetGene2. CONCLUSIONS: MYO1E mutations are not a major cause of Chinese familial SRNS in this study.

[Analysis of the relationship between clinicopathological factors and lymph node matastasis of pancreatic adenocarcinoma].

OBJECTIVE: To investigate retrospectively the relationship between clinicopathological factors and lymph node matastasis of pancreatic adenocarcinoma. METHODS: The clinicopathological factors, including gender, age, preoperative CA-19-9 level etc. of 71 patients with pancreatic adenocarcinoma were summarized to analyze the relationship between those factors and lymph node matastasis. RESULTS: Among the 71 cases, there were 49 males (69.0%) and 22 females (31.0%). Forty-eight were ≥ 60 (67.6%) and 23 were < 60 (32.4%) years old. Twenty patients had normal preoperative CA-19-9 level (28.2%) and 51 had elevated level (71.8%). The tumor in 43 (60.6%) cases located in the pancreatic head and neck, and 28 (39.4%) in the body and tail. The tumors in 8 patients were well-differentiated (11.3%), 27 were moderately differentiated (38.0%), and 36 were poorly differentiated (50.7%). The maximum diameter of the tumor was ≤ 2 cm in 11 cases (15.5%), 2 - 5 cm in 45 cases (63.4%), and > 5 cm in 15 cases (21.1%). Ten patients had tumor confined to the pancreas (14.1%), and 61 invaded peripancreatic tissues (85.9%). Vascular tumor thrombus was found in 48 cases (67.6%), and 23 cases were absent (32.4%). Thirty-six cases had lymph node matastasis (50.7%). Univariate chi-square test revealed that differentiation and range of local infiltration were significantly associated with lymph node meatstasis (P < 0.05). Multivariate logistic regression analysis also showed that differentiation and range of local infiltration were significantly associated with lymph node meatstasis (P < 0.05). CONCLUSIONS: The differentiation of tumor and range of local infiltration of pancreatic adenocarcinoma are significantly associated with lymph node metastasis. There is no significant relationship of location of the tumor, maximum diameter, presence or absence of vascular tumor thrombus with lymph node metastasis. Therefore, special attention should be paid to lymph node dissection in cases with a poorly differentiated pancreatic adenocarcinoma invading into peripancreatic tissues.

[Clinical analysis of 17 cases of gastric small cell carcinoma].

OBJECTIVE: To analyze the clinical data and prognosis of gastric small cell carcinoma (GSCC), summarize recent progress in diagnosis and therapy of this disease reported in the literature, and to provide the theoretical basis for its appropriate treatment. METHODS: Clinicopathological data of 17 patients with pathologically confirmed GSCC, treated in our hospital between 1999 to 2012, were retrospectively reviewed. RESULTS: There were 16 males and 1 female, ranged from 46 to 75 years (mean 64.6 years). The tumor was located in the gastric cardia in 13 cases, three in the gastric fundus, and one in the gastric body. All the 17 patients received surgery and 10 of them received postoperative adjuvant chemotherapy, one received preoperative adjuvant chemotherapy. Thirteen patients were followed up. Among them, two 1ived for 40 months all along, the other 3 cases died of recurrence and extensive metastasis in 6 month after operation. The median survival was 13.0 months. The median survival of the patients with and without lymph node metastasis were 42 months and 13 months, respectively. The median survival time of stage II and III patients were 24 months and 14 months, respectively. CONCLUSIONS: It is difficult to make a definite diagnosis before or during the operation for GSCC. Radical operation could be done according to other gastric cancers and lymph node dissection could be simplified. Postoperative chemotherapy with the same scheme as lung small cell carcinoma may help to improve the outcome and prolong the survival of the patients.

Subcellular localization of nucleolar protein 14 and its proliferative function mediated by miR-17-5p and E2F4 in pancreatic cancer.

Pancreatic cancer is one of the most lethal malignancies worldwide. Acquiring infinite proliferation ability is a key hallmark and basis of tumorigenesis. NOP14 is an identified ribosome biogenesis protein that plays potential roles in cell proliferation. However, the function and molecular mechanism of NOP14 remain ambiguous in most human cancers. In this study, we first investigated the subcellular localization and expression of NOP14 by multiple quantitative assays in pancreatic cancer. We confirmed that NOP14 was mainly localized in nucleolus in human pancreatic cancer cells. Then we studied the regulatory effects of this nucleolus protein on tumor cell proliferation in vitro. NOP14 was demonstrated to play a dominant pro-proliferation role in pancreatic cancer. Furthermore, we identified miR17-5p as a downstream target of NOP14. Transfection of miR17-5p mimics or inhibitors rescued the down- or upregulated effect of NOP14 on cell proliferation by regulating expression of P130. In addition, NOP14 induced expression of transcription factor E2F4 independent of miR17-5p/P130 signaling, which simultaneously activated a set of targeted genes, such as CCNE1, PIM1, AKT1 etc., to promote tumor proliferation. These findings might provide novel insights for better understanding the diverse function of NOP14 in human malignancies to develop new strategies for targeted therapy.

[Identification of occult disseminated tumor cells by recombinant herpes simplex virus expressing GFP (HSV(GFP))].

OBJECTIVE: To develop a novel rapid protocol for the detection of occult disseminated tumor cells by a recombinant herpes simplex virus expressing GFP (HSV(GFP)). METHODS: Tumor cells of seven cell lines were exposed to HSV(GFP) and then examined for GFP expression by fluorescence microscopy. Various numbers of tumor cells (10, 100, 1000, 10 000) were mixed into 2 ml human whole blood, separated with lymphocytes separation medium, exposed to HSV(GFP), incubated at 37°C for 6 - 24 h and then counted for the number of green cells under the fluorescence microscope. Some clinical samples including peripheral blood, pleural effusion, ascites, spinal fluid from tumor-bearing patients were screened using this protocol in parallel with routine cytological examination. RESULTS: HSV(GFP) was able to infect all 7 tumor cell lines indicating that the HSV(GFP) can be used to detect different types of tumor cells. The detection sensitivity was 10 cancer cells in 2 ml whole blood. In the clinical samples, there were 4/15 positive by routine cytological examination but 11/15 positive by HSV(GFP), indicating a higher sensitivity of this new protocol. CONCLUSION: Recombinant herpes simplex virus-mediated green fluorescence is a simple and sensitive technique for the identification of occult disseminated cancer cells including circulating tumor cells (CTCs).

[Treatment and prognosis of patients with duodenal gastrointestinal stromal tumors].

OBJECTIVE: To evaluate the clinical characteristics and survival factors of patients with duodenal gastrointestinal stromal tumors (GIST). METHODS: The clinical data of 41 patients with duodenal GIST were analyzed retrospectively at Cancer Hospital and Institute, Chinese Academy of Medical Sciences from June 1996 to August 2011. Kaplan-Meier method was used to calculate the recurrence-free survival rate and the Cox proportional hazard regression model employed for the recurrence-free survival analysis. RESULTS: The lesions of duodenal GIST were predominantly located in the descending (n = 26, 63.4%) and transverse portions (n = 10, 24.4%). Most duodenal GIST presented commonly with upper gastrointestinal bleeding (n = 18, 43.9%) and 12 cases (29.3%) were incidentally detected by physical examinations. Eight patients underwent pancreatoduodenectomy and 27 limited resection. The tumor size varied from 0.6 cm to 30.0 cm (mean: 8.4 cm). The recurrence-free survival rates analyzed by Kaplan-Meier method at 1, 2 and 5-year were 94.1%, 77.5% and 65.0% respectively. The results of Cox proportional hazards regression model indicated that the patients with >10/50 HP mitotic count showed a worse recurrence-free survival than those with ≤ 10/50 HP (HR = 3.7, 95%CI 1.0 - 13.7, P = 0.049). After adjusting other confounding factors, mitotic activity was one significant prognostic factor of recurrence (P = 0.024). There was no significant association between the risk of recurrence and other prognostic factors, including diagnostic age, tumor size, type of operation and the risk of aggressive behaviors (all P > 0.05). CONCLUSIONS: Mitotic activity is one prognostic factor of duodenal GIST. And R(0) resection should be regarded as an optional treatment for duodenal GIST.

Plant Salinity Sensors: Current Understanding and Future Directions.

Salt stress is a major limiting factor for plant growth and crop yield. High salinity causes osmotic stress followed by ionic stress, both of which disturb plant growth and metabolism. Understanding how plants perceive salt stress will help efforts to improve salt tolerance and ameliorate the effect of salt stress on crop growth. Various sensors and receptors in plants recognize osmotic and ionic stresses and initiate signal transduction and adaptation responses. In the past decade, much progress has been made in identifying the sensors involved in salt stress. Here, we review current knowledge of osmotic sensors and Na+ sensors and their signal transduction pathways, focusing on plant roots under salt stress. Based on bioinformatic analyses, we also discuss possible structures and mechanisms of the candidate sensors. With the rapid decline of arable land, studies on salt-stress sensors and receptors in plants are critical for the future of sustainable agriculture in saline soils. These studies also broadly inform our overall understanding of stress signaling in plants.

Root Na+ Content Negatively Correlated to Salt Tolerance Determines the Salt Tolerance of Brassica napus L. Inbred Seedlings.

Soil salinization is a major environmental stressor that reduces the growth and yield of crops. Maintaining the balance of ions under salinity is vital for plant salt tolerance; however, little is known about the correlation between the salt tolerance of crops and the ion contents of their roots and shoots. Here, we investigated the poorly understood salt-tolerance mechanisms, particularly regarding ion contents (particularly Na+), in Brassica napus subsp. napus L., an agriculturally important species. Twenty B. napus inbred lines were randomly chosen from five salt-tolerance categories and treated with increasing concentrations of NaCl (0-200 mmol) for this work. We found that the root Na+ content is the most correlated limiting factor for the salt tolerance of B. napus; the higher the salt tolerance, the lower the root Na+ content. Correspondingly, the Ca2+/Na+ and K+/Na+ ratios of the roots were highly correlated with B. napus salt tolerance, indicating that the selective absorption ability of these ions by the roots and their translocation to the shoots play a pivotal role in this trait. These data provide a foundation for the further study of the molecular mechanisms underlying salt tolerance and for breeding salt-tolerant B. napus cultivars.

ALDH2C4 regulates cuticle thickness and reduces water loss to promote drought tolerance.

In Arabidopsis thaliana, ALDH2C4 encodes coniferaldehyde dehydrogenase, which oxidizes coniferaldehyde to ferulic acid. Drought stress is one of the important abiotic stresses affecting plant growth. However, the role of ferulic acid in drought resistance is unknown. To investigate the contribution of ferulic acid to cuticle composition and drought resistance, we used two Arabidopsis aldh2c4 mutant lines. Compared with wild-type (WT) leaves, ferulic acid contents were significantly lower (by more than 50 %) in mutants. The mutants also had lower amounts of cutin and wax, primarily due to reductions in C18:2 dioic acid and alkanes, respectively. Furthermore, the leaves of the mutant plants exhibited greater rates of water loss and released chlorophyll faster than WT leaves when immersed in 80 % ethanol, indicating a defective cuticle barrier. The growth of aldh2c4 mutants was severely inhibited, and their leaves showed a higher degree of wilting relative to the WT plants under drought conditions. In aldh2c4 complementation lines, the growth inhibition of the mutant plants under drought stress was alleviated. Taken together, our results demonstrate that ferulic acid plays an important role in the composition and structural properties of the cuticle and that a ferulic acid deficiency in the cutin leads to reduced drought tolerance.

[Value of intraoperative radiotherapy in the treatment of locally advanced pancreatic cancer].

OBJECTIVE: To assess the value of intraoperative radiotherapy (IORT) in the combined treatment of locally advanced pancreatic cancer. METHODS: All patients with locally advanced pancreatic cancer at our hospital from January 2007 to December 2009, judged as unresectable and confirmed by histology or cytology, were recruited into this prospective study. They were randomly assigned into the IORT group (n=31) and control group (n=34). The IORT group received IORT plus internal drainage or laparotomy. The control group had internal drainage or laparotomy only. The evaluation of adverse results of two groups included: intraoperative and postoperative adverse events, recent post-operative side effects, analgesic effect, the level of tumor marker such as CA19-9 and the long-term survival. RESULTS: There was no difference in operation duration, intraoperative hemorrhage and postoperative recovery. Significant differences were found in hematotoxicology, analgesic effect, tumor marker decreasing and long-term survival. CONCLUSION: IORT is a safe, reliable and easy-to-master technique without any obvious side effect. Its analgesic effect is better than the control group. Also IORT can retard the tumor growth and improve the patient survival.

Combination of preoperative fibrinogen and D-dimer as a prognostic indicator in pancreatic ductal adenocarcinoma patients undergoing R0 resection.

BACKGROUND: Patients with malignant tumors frequently exhibit hyperactivation of the coagulation system and secondary increased fibrinolytic activity. Fibrinogen and D-dimer are common indicators that are crucial in the coagulation/fibrinolysis system. Both indicators have been verified to have predictive value in the overall survival (OS) of many patients with solid malignancies. AIM: To explore the prognostic significance of fibrinogen combined with D-dimer in pancreatic ductal adenocarcinoma (PDAC) patients undergoing radical R0 resection. METHODS: We retrospectively analyzed the clinical data of 282 patients with PDAC undergoing radical R0 resection in the Cancer Hospital, Chinese Academy of Medical Sciences, between January 2010 and December 2019. The surv_cutpoint function of R language was used to determine the optimal cutoff values of the preoperative fibrinogen concentration and preoperative D-dimer concentration. Enrolled patients were further divided into the any-high group (high preoperative fibrinogen concentration and/or high preoperative D-dimer concentration) and the low-low group (low preoperative fibrinogen and D-dimer concentrations) according to the optimal cutoff values. RESULTS: The optimal cutoff values of the preoperative fibrinogen concentration and preoperative D-dimer concentration were 3.31 g/L and 0.53 mg/L, respectively. Furthermore, multivariate Cox regression analysis showed that the preoperative fibrinogen concentration (HR: 1.603, 95%CI: 1.201-2.140, P = 0.001) and preoperative D-dimer concentration (HR: 1.355, 95%CI: 1.019-1.801, P = 0.036) exhibited obvious correlations with the OS of PDAC patients undergoing radical R0 resection. A prognostic analysis was further performed based on the subgroup results by using fibrinogen combined with D-dimer. The median OS duration of the low-low group (31.17 mo) was significantly longer than that of the any-high group (15.43 mo). Additionally, multivariate Cox regression analysis revealed that the degree of differentiation (P < 0.001), lymph node metastasis (HR: 0.663, 95%CI: 0.497-0.883, P = 0.005), preoperative CA19-9 level (HR: 1.699, 95%CI: 1.258-2.293, P = 0.001), adjuvant therapy (HR: 1.582, 95%CI: 1.202-2.081, P = 0.001) and preoperative combined grouping (HR: 2.397, 95%CI: 1.723-3.335, P < 0.001) were independent predictors of OS in PDAC patients undergoing radical R0 resection. CONCLUSION: Preoperative fibrinogen combined with D-dimer plays a predictive role in OS, and low preoperative fibrinogen and D-dimer concentrations can indicate prolonged OS in PDAC patients undergoing radical R0 resection.

[The role of slow-release 5-fluorouracil implantation in treatment of unresectable pancreatic cancer].

OBJECTIVE: To study the role of slow-release 5-fluorouracil implantation in treatment of unresectable pancreatic cancer. METHODS: 85 cases of untreated patients with locally advanced pancreatic cancer (LAPC) were randomized into two groups: Trial group: slow-release 5-fluorouracil implantation (50 patients) and control group (35 patients). Observing the objective tumor response, clinical benefit response, toxicity, complications and survival of patients of the two groups. RESULTS: In the trial group the overall response rate (PR + NC) was 76.0%, and the clinical benefit response rate was 52.0%. No toxicity was observed. Pancreatic fistula occurred in 2 patients. The median survival time of the two groups was 9.0 months and 4.0 months, respectively. The survival rates of 6- and 12-month were 56.8% vs. 31.4% and 22.9% vs. 2.9% in the two groups, respectively (P = 0.012). CONCLUSION: Slow-release 5-fluorouracil implantation is a simple, safe and effective method in treatment of LAPC.

[Surgical treatment of acute pulmonary embolism].

OBJECTIVE: To evaluate the clinical value of surgical treatment for acute pulmonary embolism under shallow low temperature cardiopulmonary bypass. METHODS: From April 2004 to October 2009, the data of 12 inpatients with acute pulmonary embolism were analyzed. Deep vein thrombosis was present in all patients. There were unilateral pulmonary embolism (n=7), bilateral pulmonary embolism (n=5), shock (n=5); heart function class III (n=7) and heart function class IV (n=5). The average time from onset to surgery was 9 hours. RESULTS: Among all cases, no recurrence was observed. All showed normal heart function and fully resumed manual labor. CONCLUSION: Surgical thrombectomy for acute pulmonary embolism has an excellent clinical efficacy. Its routine use should be encouraged.

[Comparison of clinicopathological characteristics between colorectal signet-ring cell carcinoma and mucinous adenocarcinoma].

OBJECTIVE: To compare the difference of clinicopathological characteristics between colorectal signet-ring cell carcinoma and mucinous adenocarcinoma. METHODS: The clinicopathological and survival data of 65 patients with colorectal signet-ring carcinoma and 166 with mucinous adenocarcinoma were retrospectively analyzed. RESULTS: Such clinical characteristics as gender, gross anatomical classification, preoperative carcinoembryonic antigen level and hepatic metastasis or not had no significant difference between two groups (P > 0.05) while the difference of such characteristics as age, location of tumor, vascular tumor embolus, N stage, T stage, AJCC stage, preoperative obstruction and the ratio of radical resection between them was significant (P < 0.05). The overall 3, 5-year survival of the whole group was 56.7% and 31.6% respectively. The 3, 5-year survival and median survival time (MST) in the signet-ring cell carcinoma and the mucinous adenocarcinoma groups were 33.1%, 14.8%, 24.0 months and 64.1%, 36.6%, 41.5 months respectively. The pathological type of signet-ring cell carcinoma was an independent risk factor of survival in the whole group. CONCLUSION: Compared to colorectal mucinous adenocarcinoma, signet-ring cell carcinoma has a higher degree of malignancy and the patients have a worse survival.

[Clinical and pathological analysis of 114 cases with non-ductal pancreatic adenocarcinoma occupying lesions].

OBJECTIVE: To improve the diagnosis and treatment of non-ductal pancreatic adenocarcinoma-occupying lesions. METHODS: A retrospective analysis was made for 114 cases of pancreatic non-ductal adenocarcinoma-occupying pathologically confirmed lesions. RESULTS: (1) There were 36 males (31.6%) and 78 females (68.42%); (2) presenting symptoms and signs were abdominal pain (n = 56, 49.1%), back pain (n = 24, 21.1%), weight loss (n = 18, 15.8%) and obstructive jaundice (n = 8, 0.07%); (3) the positive rates of CA19-9, CA242 and CEA were 21.1%, 19.7% and 5.6% respectively; (4) pancreaticoduodenectomy was performed in 26 patients, distal pancreatectomy in 53, tumor enucleation in 15, segmental pancreatectomy in 9, partial resection in 3, duodenum-preserving pancreatic head resection in 1 and palliative surgery (either cholecystojejunostomy anastomosis or gastrojejunostomy) in 7; (5) pathologic analysis revealed 35 solid pseudopapillary neoplasm of pancreas, 28 pancreatic endocrine tumors, 18 focal chronic pancreatitis, 11 serous cystic neoplasms, 9 mucinous cystic neoplasms, 4 pancreatic cysts, 3 acinar cell carcinomas, 2 pancreatic cavernous hemangiomas, 1 sarcoma of pancreas, 1 sarcomatoid carcinoma of pancreas, 1 pancreatic schwannoma and 1 pancreatic neuroblastoma. CONCLUSION: The non-ductal pancreatic adenocarcinoma-occupying lesions have no specific clinical presentation or serum tumor marker. An understanding of the natural history of these lesions is important for optimal management.

[Role of 125I seed implantation in treatment of unresectable pancreatic cancer].

OBJECTIVE: To study the role of (125)I seed implantation in the treatment of unresectable pancreatic cancer. METHODS: From April 2004 to march 2006, 66 untreated patients with locally advanced pancreatic cancer (LAPC) were randomized into two groups: Group A: (125)I seeds implantation (n = 31) and Group B: control (n = 34). The objective tumor response, clinical benefit response, toxicity, complications and survival of two groups were observed. RESULTS: In Group A, the overall response rate (PR + NC) was 80.6%. Clinical benefit response rate was 54.8%. No toxicity was observed. Gastrointestinal hemorrhage and pancreatic fistula occurred in 1 patient respectively in Group A. The survival rates of 6 and 12 months were 56.0% vs 31.4% and 16.8% vs 2.9% respectively in two groups (P < 0.05). The median survival time of two groups was 8.0 months vs 4.0 months (P < 0.05). CONCLUSION: (125)I seed implantation is a simple, safe and effective method in the treatment of locally advanced pancreatic cancer.

Development and validation of a novel nomogram for predicting the prognosis of patients with resected pancreatic adenocarcinoma.

The survival prediction for patients with resected pancreatic adenocarcinoma by using the Tumor-Node-Metastasis (TNM) staging system remains limited. A nomogram is a efficient tool that can be used to predict the outcome of patients with various types of malignancy. The present study aimed to develop and validate a nomogram for patients with resected pancreatic adenocarcinoma. A total of 368 patients (258 in the training set and 110 in the validation set) who underwent pancreatic adenocarcinoma resection at the China National Cancer Center between January 2008 and October 2018 were included in the present study. The nomogram was established according to the results from Cox multivariate analysis, which was validated by discrimination and calibration. The area under the receiver operating characteristic curve (AUC) was determined to assess the accuracy of survival predictions. The results from multivariate analysis in the training set demonstrated that blood transfusion, T-stage, N-stage, tumor grade, capsule invasion, carbohydrate antigen 199, neutrophil percentage and adjuvant therapy were independent prognostic factors for overall survival (OS; all P<0.05). Subsequently, a nomogram predicting the 1-year, 3-year and 5-year OS rates, with favorable calibration, was established based on the independent prognostic factors. The concordance indices of the nomogram were higher compared with the TNM staging system in both training and validation sets. Furthermore, a clear risk stratification system based on the nomogram was used to classify patients into the three following groups: Low-risk group (≤168), moderate-risk group (168-255) and high-risk group (>255). The risk stratification system demonstrated an improved ability in predicting the 1-year, 3-year and 5-year OS rates compared with the TNM system (AUC, 0.758, 0.709 and 0.672 vs. AUC, 0.614, 0.604 and 0.568; all P<0.05). The present study developed and validated a nomogram for patients with resected pancreatic adenocarcinoma by including additional independent prognostic factors, including tumor marker, immune index, surgical information, pathological data and adjuvant therapy. Taken together, the results from the present study indicated an improved performance of the nomogram in predicting the prognosis of patients with resected pancreatic adenocarcinoma compared with the TNM staging system.

Prognostic value of the preoperative fibrinogen-to-albumin ratio in pancreatic ductal adenocarcinoma patients undergoing R0 resection.

BACKGROUND: Inflammation plays an important role in tumor progression, and growing evidence has confirmed that the fibrinogen-to-albumin ratio (FAR) is an important prognostic factor for overall survival in malignant tumors. AIM: To investigate the prognostic significance of FAR in patients undergoing radical R0 resection of pancreatic ductal adenocarcinoma (PDAC). METHODS: We retrospectively analyzed the data of 282 patients with PDAC who underwent radical R0 resection at The Cancer Hospital of the Chinese Academy of Medical Sciences from January 2010 to December 2019. The surv_cutpoint function of the R package survminer via RStudio software (version 1.3.1073, http://www.rstudio.org) was used to determine the optimal cut-off values of biological markers, such as preoperative FAR. The Kaplan-Meier method and log-rank tests were used for univariate survival analysis, and a Cox regression model was used for multivariate survival analysis for PDAC patients who underwent radical R0 resection. RESULTS: The optimal cut-off value of FAR was 0.08 by the surv_cutpoint function. Higher preoperative FAR was significantly correlated with clinical symptoms (P = 0.001), tumor location (P < 0.001), surgical approaches (P < 0.001), preoperative plasma fibrinogen concentration (P < 0.001), and preoperative plasma albumin level (P < 0.001). Multivariate analysis showed that degree of tumor differentiation (P < 0.001), number of metastatic lymph nodes [hazard ratio (HR): 0.678, 95% confidence interval (CI): 0.509-0.904, P = 0.008], adjuvant therapy (HR: 1.604, 95%CI: 1.214-2.118, P = 0.001), preoperative cancer antigen 19-9 level (HR: 1.740, 95%CI: 1.288-2.352, P < 0.001), and preoperative FAR (HR: 2.258, 95%CI: 1.720-2.963, P < 0.001) were independent risk factors for poor prognosis in patients with PDAC who underwent radical R0 resection. CONCLUSION: The increase in preoperative FAR was significantly related to poor prognosis in patients undergoing radical R0 resection for PDAC. Preoperative FAR can be used clinically to predict the prognosis of PDAC patients undergoing radical R0 resection.