[Current status and prospects of neoadjuvant therapy for resectable pancreatic cancer].

Pancreatic cancer is a highly malignant tumor. About 75% of patients with pancreatic cancer who underwent radical surgical resection will still experience postoperative recurrence. Neoadjuvant therapy could improve outcomes in patients with borderline resectable pancreatic cancer,has become a consensus;however it is still controversial in resectable pancreatic cancer. Limited high-quality randomized controlled trial studies support the routine initiation of neoadjuvant therapy in resectable pancreatic cancer. With the development of new technologies, such as next-generation sequencing, liquid biopsy, imaging omics, and organoids, patients are expected to benefit from the precision screening of potential candidates for neoadjuvant therapy and individualized treatment strategy.

[Implementation and controversies of enhanced recovery after surgery in pancreaticoduodenectomy].

The concept of enhanced recovery after surgery(ERAS) has been widely accepted and applied in clinical practice.However,as one of the most complex surgical procedures in abdominal surgery,pancreaticoduodenectomy is characterized by long operation time,high incidence rate of postoperative complications and delayed recovery,there still remain some controversies about application of ERAS approaches in perioperative managements of pancreaticoduodenectomy.Although more and more studies has revealed the safety and efficacy of ERAS approaches in pancreaticoduodenectomy,the implementation of ERAS approaches should be still individualized in clinical practice to ensure safety of the patients.

[The comparison of prognosis and risk factors after radical resection for pancreatic ductal adenocarcinoma between China Pancreas Data Center and SEER].

Objectives: To compare the prognosis of patients underwent radical resection for pancreatic ductal adenocarcinoma(PDAC) in Surveillance, Epidemiology, and End Results(SEER) and China Pancreas Data Center(CPDC), and to compare the prognostic factors for PDAC in both databases. Methods: The data of patients underwent radical resection for PDAC in CPDC database from January 2016 to December 2017 and SEER database from January 2014 to December 2015 were retrospectively analyzed. The prognosis of patients in both databases was analyzed by the Kaplan-Meier method, Log-rank method, and propensity score matching, and the Cox proportional hazard regression was used to analyze the independent prognosis factors for PDAC. Results: There were 1 977 cases and 2 220 cases of pancreatic cancer that underwent radical resection from CPDC and SEER, respectively. There were more male patients(60.90%,1 204/1 977) than female patients(39.10%,773/1 977) in CPDC, while nearly 1∶1 ratio(male:1 112 cases,female:1108)was observed between male and female in SEER(χ²=48.977,P<0.01). The proportion of patients under 45 years old was the smallest in both databases, and the age group with the most significant proportion was 60 to 74 years old. The ratio of patients over 75 years old in the SEER(24.28%,539/2 220) was higher than that of CPDC(7.89%,156/1 977)(χ²=202.090,P<0.01), while the proportion of patients between 45 and 59 years old in CPDC(33.69%,666/1 977) was higher than that in SEER(19.77%,439/2 220)(χ²=103.640,P<0.01). There were more pancreatic head cancers than body and tail cancers in both databases, and no statistical difference was found in tumor size between the two databases (W=2 181 502,P=0.740). More positive and examined lymph nodes were found in SEER patients (W=3 265 131,W=2 954 363,all P<0.01); and the proportion of patients who had at least 15 lymph nodes dissected was higher in SEER(63.24%,1 404/2 220)(χ²=532.130,P<0.01). There were more patients without neoadjuvant or adjuvant therapy in CPDC(57.16%,1 130/1 977) than that in SEER(24.91%,553/2 220)(χ²=451.390,P<0.01). After propensity score matching, the overall survival for CPDC was better than that for SEER(Log-rank test:χ²=4.500,P=0.034), and the median overall survival was 24 months and 23 months respectively. Cox regressional analysis showed the common independent prognosis factors in both databases were ≥75 years old, pancreatic head cancer, poorly differentiated and undifferentiated tumors, T stage, N stage(All P<0.05). Neoadjuvant or adjuvant therapy was a protective factor in both databases(CPDC:Wald=27.082;SEER:Wald=212.285, all P<0.01) and 45 to 59 years old was protective factor in the SEER database(Wald=5.212,P=0.020). Conclusions: The data in both databases have a good consistency. However, in terms of data quality, examined lymph nodes count, and neoadjuvant/adjuvant therapy rate, the CPDC differs greatly from the SEER.

[Circulating tumor cells in pancreatic cancer patients: progression in the detection methods and clinical application].

Circulating tumor cells (CTC) disseminate from primary tumors by undergoing epithelial mesenchymal transition that allow their entry into the circulation to drive metastatic formation in pancreatic cancer patients.Technological advances in detection and characterization of CTC are conducive to the early diagnosis, differential diagnosis, monitoring disease progression and predicating the probability of canceration or the chemotherapeutic efficacy. Nowadays, detection methods of CTC can be based on immunomagnetic beads technique, cell filtration or microfluidic chips technology, but there are great differences in the sample throughput, CTC recovery rate, purity, and CTC viability among them.Owing to the dilemma in detection methods, the intrinsic relevance between the biological characteristics of CTC and clinical manifestations is still not exactly elucidated. By the improved methodology, next generation sequencing technology and exploring the technique for culturing CTC in vitro and establishing xenotransplanted tumor model in nude mice, more and more biological information will be revealed, and finally, individualized treatment is achieved.

[Diagnosis and treatment of pancreatic neuroendocrine neoplasmas in Von Hippel-Lindau syndrome].

Von Hippel-Lindau(VHL) syndrome is a rare autosomal dominant hereditary disease, and pancreas is one of the frequently involved intra-abdominal organs, including simple pancreatic cysts, pancreatic serous cystadenomas and neuroendocrine neoplasmas. Most of the VHL-related pancreatic neuroendocrine neoplasmas (VHL-pNEN)were non-functional, but they still have a tendency to be malignant. Treatment options for VHL-pNEN include regular follow-up, surgical resection, and medication therapy. When compared with sporadic pNEN, the malignant degree of VHL-pNEN is lower, with a better prognosis, so the surgical treatment should be carefully considered. The indications of surgery for VHL-pNEN include big primary lesions (≥3 cm), fast tumor doubling time (<500 days), VHL gene mutation on exon 3, malignant manifestations on imaging findings, and functional pNEN lesions. The function-preserving approach should be performed to keep the functional pancreatic parenchyma as much as possible. Even for patients with a late stage malignancy that cannot be radically resected, active medication therapy may still lead to a long-term survival.

[Surgical treatment of pancreatic cystic neoplasms: follow-up or surgical intervention].

Pancreatic cystic neoplasm(PCN) are common and increasingly detected in recent years including serous cystic neoplasms, mucinous cystic neoplasms, intraductal papillary mucinous neoplasms, solid pseudopapillary neoplasms and cystic pancreatic neuroendocrine tumors.Some of PCN have a low risk of malignancy while others have a high risk and need interventions, even in the same type of cystic neoplasms. The management of PCN requires risk stratification for malignant potential, and clinicians should have a systematic approach for establishing a diagnosis and determining which patients require surgical treatment. Under the guidance of minimally invasive surgery, some organ preserving procedures including tumor enucleation, segmental pancreatic resection, duodenum-preserving total or subtotal pancreatic head resection, and spleen-preserving pancreatic body and tail resection are recommended for treatment of PCN. The indications for follow-up or surgical intervention for treatment of PCN patients should be mastered strictly to avoid either insufficient- or over-treatment.

HCCS1 inhibits the stemness of human pancreatic cancer stem-like cells.

OBJECTIVE: SW1990-spheroid enrichment (SW1990-SE) cells were isolated using a new type of consecutive spheroid enrichment in this study. Cell surface markers were determined by flow cytometry for identification. In vivo tumorigenicity was applied by subcutaneous transplantation in nude mice for verifying the stemness characteristics of SW1990-SE cells. MATERIALS AND METHODS: SW1990-SE cells were subjected to lentivirus infection for establishing the SW1990-SE cell line stably low-expressing HCCS1 (SW1990-SE-shHCCS1) and negative control cell line (SW1990-SE-LV3NC). The stemness regulatory effects of HCCS1 on SW1990-SE cells were evaluated by cell counting kit-8 (CCK-8) assay and 96-wells plate single cell cloning assay in vitro. Subcutaneous transplantation in nude mice was conducted for evaluating the in vivo stemness regulation of HCCS1 on SW1990-SE cells.. RESULTS: HCCS1 knockdown in SW1990-SE cells did not markedly change the cell proliferation and doubling time, whereas the in vitro spheroid diameter and single cell cloning efficacy remarkably increased. In vivo experiments showed that HCCS1 knockdown greatly enhanced the tumorigenicity of SW1990-SE cells in nude mice. CONCLUSIONS: This study first obtains the human pancreatic cancer stem-like cells SW1990-SE through consecutive spheroid enrichment. Both in vivo and in vitro experiments verified that HCCS1 knockdown largely enhanced the stemness of SW1990-SE cells. Our study provides an important reference for the research of tumor stem cells.

MiR-137 and its target TGFA modulate cell growth and tumorigenesis of non-small cell lung cancer.

OBJECTIVE: MiR-137 has been reported to serve as a tumor suppressor in non-small cell lung cancer (NSCLC). However, the potential mechanism remains largely unclear. The present study aimed to explore the potential molecular mechanisms by which miR-137 regulated NSCLC. MATERIALS AND METHODS: Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was used to quantify the expression levels of miR-137 in NSCLC tissues and cell lines. Dual-luciferase reporter assay was employed to confirm the specificity of miR-137 target genes. An MTT assay and flow cytometry were used to determine the rates of cell proliferation and cell cycle distribution. Furthermore, the effect of miR-137 up-regulation on TGFA expression was examined by western blot. RESULTS: miR-137 expression levels in NSCLC cell lines or tissue were significantly lower than in a normal human lung cell line or adjacent normal tissues. We further found that upregulation of miR-137 inhibited the proliferation of NSCLC cells, whereas silencing of miR-137 promoted the proliferation of NSCLC. Moreover, we identified TGFA as a direct target gene of miR-137 in NSCLC cell. Finally, Similarly, knockdown of TGFA led to the suppression of NSCLC cell proliferation. CONCLUSIONS: Overall, our findings indicated that miR-137 served as a tumor suppressor in NSCLC and its suppressive effect is mediated by repressing TGFA expression.

Prognostic and diagnostic significance of long non-coding RNA AGAP2-AS1 levels in patients with non-small cell lung cancer.

OBJECTIVE: The purpose of this study was to explore whether long non-coding RNA AGAP2-AS1 (AGAP2-AS1) could serve as a novel biomarker for non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Cancer and matched normal lung tissues were collected from 198 patients. AGAP2-AS1 levels were examined by RT-PCR, and the associations of AGAP2-AS1 levels with clinicopathological characteristics evaluated. Overall survival was evaluated using the Kaplan-Meier method. Cox proportional hazard modeling was performed for univariate and multivariate analysis to determine the effects of variables on survival. Receiver-operating characteristic. Besides, the receiver operating characteristic (ROC) curve analysis were applied to analyze its diagnostic value. RESULTS: Expression of AGAP2-AS1 was up-regulated in the NSCLC tissues compared with the adjacent normal tissues (p < 0.01). Furthermore, The level of AGAP2-AS19 in NSCLC was strongly correlated with tumor stage (p = 0.001) and lymph nodes metastasis (p = 0.005). Kaplan-Meier analysis demonstrated patients with higher AGAP2-AS1 expression had a shorter overall survival time than those with lower AGAP2-AS1 expression (p < 0.0001). The multivariate analysis showed that AGAP2-AS1 expression is an independent prognostic factor of overall survival in patients with NSCLC. The results of ROC curve analysis showed that AGAP2-AS1 might be a promising diagnostic marker of NSCLC with an AUC of 0.846. CONCLUSIONS: Our findings revealed that AGAP2-AS1 might be a potential biomarker for the diagnosis and prognosis of NSCLC. However, to completely elucidate its role as a biomarker, further studies are required.

Regulation of Twist in the metastasis of non-small cell lung cancer by miR-92b.

OBJECTIVE: It is well documented that some microRNAs (miRNAs) regulates tumorigenesis and cancer metastases of non-small cell lung cancer (NSCLC). Nevertheless, a role of miR-92b in control of the metastasis of NSCLC has not been acknowledged. MATERIALS AND METHODS: Here, we reported that miR-92b levels were significantly decreased and Twist levels were significantly increased in NSCLC specimens, compared to paired adjacent non-tumor lung tissue. Moreover, the levels of miR-92b and Twist inversely correlated. RESULTS: Bioinformatics analyses and luciferase-reporter assay showed that miR-92b targeted the 3'-UTR of Twist mRNA to inhibit its translation. Overexpression of miR-92b inhibited Twist-mediated cell invasiveness, while depletion of miR-92b increased Twist-mediated cell invasiveness in either a transwell cell migration assay or a scratch wound healing assay. CONCLUSIONS: Together, our data suggest that re-expression of miR-92b may inhibit Twist-mediated NSCLC metastasis.