With the improvement of nonsurgical treatment in pancreatic cancer, the increasing accuracy of subclassification of anatomy, and the continuous refinement of surgical resection techniques, more and more locally advanced pancreatic cancer(LAPC) patients have the opportunity to undergo conversion surgery and achieve survival benefits,which has attracted the attention of scholars in this field. Despite the numerous prospective clinical studies conducted, there is still a lack of high-level evidence-based medical evidence in terms of conversion treatment strategies, efficacy evaluation, surgical timing and survival prognosis, and there are not yet specific quantitative standards and guiding principles for conversion treatment for these patients in clinical practice, and the indications for surgical resection rely more on the experience of each center or surgeon, lacking consistency. Therefore,the indicators for the evaluation of the efficacy of conversion treatment in patients with LAPC were summarized to reflect on the different modes of conversion treatment and clinical outcomes currently being explored, expecting to provide more accurate recommendations and guidance for the clinic.
Humans ; Prospective Studies ; Pancreatic Neoplasms/drug therapy* ; Neoadjuvant Therapy ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use*

A 68-year-old male was admitted due to fatigue and poor appetite and diagnosed pathologically as pancreatic adenocarcinoma with liver metastasis. The tumor marker carbohydrate antigen 199 (CA199) level was 2003.4 U/mL. The patient received two cycles of modified FOLFIRINOX plus immune checkpoint inhibitor (penpulimab). However, the tumor did not shrink and CA199 level was even higher. Anlotinib was added from the 3rd cycle, and the size of primary tumor and metastatic lesions were significantly reduced. Laparoscopic distal pancreatectomy and splenectomy as well as liver metastasis resection was performed. Three cycles of combined therapy were adopted after surgery followed by maintenance therapy with anlotinib plus penpulimab. There was no evidence of tumor recurrence during the follow-up (nearly 19 months since diagnosis).
Male ; Humans ; Aged ; Pancreatic Neoplasms/drug therapy* ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Adenocarcinoma ; Neoplasm Recurrence, Local/surgery* ; Immunotherapy ; Liver Neoplasms/therapy* ; Pancreatectomy

This study aims to investigate the effect and mechanism of saikosaponin D on the proliferation, apoptosis, and autophagy of pancreatic cancer Panc-1 cells. The cell counting kit(CCK-8) was used to examine the effects of 7, 10, 13, 16, 19, 22, 25, and 28 μmol·L~(-1) saikosaponin D on the proliferation of Panc-1 cells. Three groups including the control(0 μmol·L~(-1)), low-concentration(10 μmol·L~(-1)) saikosaponin D, and high-concentration(16 μmol·L~(-1)) saikosaponin D groups were designed. The colony formation assay was employed to measure the effect of saikosaponin D on the colony formation rate of Panc-1 cells. The cells treated with saikosaponin D were stained with hematoxylin-eosin(HE), and the changes of cell morphology were observed. Hoechst 33258 fluorescent staining was used to detect the effect of saikosaponin D on the cell apoptosis. The autophagy staining assay kit with MDC was used to examine the effect of saikosaponin D on the autophagy of Panc-1 cells. Western blot and immunocytochemistry(ICC) were employed to examine the effect of saikosaponin D on the expression levels and distribution of B-cell lymphoma-2(Bcl-2), Bcl-2-associated X protein(Bax), cysteine-aspartic acid protease-3(caspase-3), cleaved caspase-3, autophagy-associated protein Beclin1, microtubule-associated protein light chain 3(LC3), protein kinase B(Akt), phosphorylated protein kinase B(p-Akt), mammalian target of rapamycin(mTOR), and phosphorylated mammalian target of rapamycin(p-mTOR). The results showed that compared with the control group, saikosaponin D decreased the proliferation rate of Panc-1 cells in a dose-dependent and time-dependent manner. The colony formation rate of the cells significantly decreased after saikosaponin D treatment. Compared with the control group, the cells treated with saikosaponin D became small, accompanied by the formation of apoptotic bodies. The saikosaponin D groups showed increased apoptosis rate and autophagic vesicle accumulation. Compared with the control group, saikosaponin D up-regulated the expression of Bax, cleaved caspase3, Beclin1, LC3Ⅱ/LC3Ⅰ and down-regulated the expression of Bcl-2, caspase-3, p-Akt/Akt, and p-mTOR/mTOR. In addition, these proteins mainly existed in the cytoplasm. In conclusion, saikosaponin D can inhibit the proliferation and induce the apoptosis and autophagy of Panc-1 cells via inhibiting the Akt/mTOR pathway.
Humans ; Proto-Oncogene Proteins c-akt/genetics* ; Caspase 3 ; bcl-2-Associated X Protein ; Beclin-1/pharmacology* ; Cell Line, Tumor ; TOR Serine-Threonine Kinases/genetics* ; Apoptosis ; Pancreatic Neoplasms/drug therapy* ; Caspases ; Autophagy

To investigate whether chemotherapy could prolong the postoperative survival time in patients with early stages pancreatic ductal adenocarcinoma (PDAC). A total of 5280 stage ⅠA -ⅡB PDAC patients diagnosed from 2010 to 2015 were selected from surveillance，epidemiology，and end results (SEER) database. Propensity score matching (PSM) analysis was adopted to reduce the baseline differences between the groups. Univariate survival analysis was conducted with the Kaplan-Meier method. Multivariate survival analysis was performed with the Cox proportional hazards model. Univariate and multivariate survival analyses showed that age, differentiation, stage, chemotherapy were independent risk factors for the survival of PDAC patients. After PSM, it is found that adjuvant chemotherapy could prolong the median overall survival time (mOS) for stage ⅠB, ⅡA and ⅡB patients. However, for stage ⅠA patients, there were no significant differences in 3-year survival rate and mOS between patients with chemotherapy (=283) and without chemotherapy (=229) (57.4% vs 55.6%, vs all >0.05). Further analyses show that among 101 patients with well differentiated PDAC and 294 patients with moderately differentiated PDAC, there were no significant differences in survival rate and mOS between patients with and without chemotherapy (all >0.05). Among 117 patients with low-differentiated + undifferentiated PDAC, 3-year survival rate and mOS in patients with chemotherapy were significantly better than those without chemotherapy (48.5% vs 34.1%, vs all <0.05). Chemotherapy regimen used currently is not beneficial for patients with moderately and well differentiated stage ⅠA PDAC, but it is an independent prognostic factor for low-differentiated + undifferentiated PDAC patients.
Adenocarcinoma/pathology* ; Carcinoma, Pancreatic Ductal/surgery* ; Chemotherapy, Adjuvant ; Humans ; Neoplasm Staging ; Pancreatic Neoplasms/drug therapy* ; Prognosis ; Propensity Score

Pancreatic ductal adenocarcinoma (PDAC) is an extremely malignant disease, which has an extremely low survival rate of <9% in the United States. As a new hallmark of cancer, metabolism reprogramming exerts crucial impacts on PDAC development and progression. Notably, arginine metabolism is altered in PDAC cells and participates in vital signaling pathways. In addition, arginine and its metabolites including polyamine, creatine, agmatine, and nitric oxide regulate the proliferation, growth, autophagy, apoptosis, and metastasis of cancer cells. Due to the loss of argininosuccinate synthetase 1 (ASS1) expression, the key enzyme in arginine biosynthesis, arginine deprivation is regarded as a potential strategy for PDAC therapy. However, drug resistance develops during arginine depletion treatment, along with the re-expression of ASS1, metabolic dysfunction, and the appearance of anti-drug antibody. Additionally, arginase 1 exerts crucial roles in myeloid-derived suppressor cells, indicating its potential targeting by cancer immunotherapy. In this review, we introduce arginine metabolism and its impacts on PDAC cells. Also, we discuss the role of arginine metabolism in arginine deprivation therapy and immunotherapy for cancer.
Arginine/metabolism* ; Argininosuccinate Synthase ; Carcinoma, Pancreatic Ductal/drug therapy* ; Cell Line, Tumor ; Humans ; Pancreatic Neoplasms/drug therapy*

OBJECTIVE: To retrospectively evaluate the safety and efficacy of percutaneous radiofrequency ablation (RFA) in patients with metachronous hepatic metastases arising from pancreatic adenocarcinoma who had previously received curative surgery.MATERIALS AND METHODS: Between 2002 and 2017, percutaneous RFA was performed on 94 metachronous hepatic metastases (median diameter, 1.5 cm) arising from pancreatic cancer in 60 patients (mean age, 60.5 years). Patients were included if they had fewer than five metastases, a maximum tumor diameter of ≤ 5 cm, and disease confined to the liver or stable extrahepatic disease. For comparisons during the same period, we included 66 patients who received chemotherapy only and met the same eligibility criteria described.RESULTS: Technical success was achieved in all hepatic metastasis without any procedure-related mortality. During follow-up, local tumor progression of treated lesions was observed in 38.3% of the tumors. Overall median survival and 3-year survival rates were 12 months and 0%, respectively from initial RFA, and 14.7 months and 2.1%, respectively from the first diagnosis of liver metastasis. Multivariate analysis showed that a large tumor diameter of > 1.5 cm, a late TNM stage (≥ IIB) before curative surgery, a time from surgery to recurrence of < 1 year, and the presence of extrahepatic metastasis, were all prognostic of reduced overall survival after RFA. Median overall (12 months vs. 9.1 months, p = 0.094) and progression-free survival (5 months vs. 3.3 months, p = 0.068) were higher in the RFA group than in the chemotherapy group with borderline statistical difference.CONCLUSION: RFA is safe and may offer successful local tumor control in patients with metachronous hepatic metastases arising from pancreatic adenocarcinoma. Patients with a small diameter tumor, early TNM stage before curative surgery, late hepatic recurrence, and liver-only metastasis benefit most from RFA treatment. RFA provided better survival outcomes than chemotherapy for this specific group with borderline statistical difference.
Adenocarcinoma ; Catheter Ablation ; Diagnosis ; Disease-Free Survival ; Drug Therapy ; Follow-Up Studies ; Humans ; Liver ; Mortality ; Multivariate Analysis ; Neoplasm Metastasis ; Pancreatic Neoplasms ; Recurrence ; Retrospective Studies ; Survival Rate

Family history of pancreatic cancer (PC) is a risk factor for PC development, and the risk level correlates with the number of affected families. A case of PC with ≥1 PC cases in the first-degree relative is broadly defined as familial pancreatic cancer (FPC) and accounts for 5% to 10% of total PC cases. FPC possesses several epidemiological, genetic and clinicopathological aspects that are distinct from those of conventional PCs. In Western countries, FPC registries have been established since the 1990s, and high-risk individuals are screened to detect early PCs. For the pharmacotherapy of FPC, especially in cases with germline pathogenic BRCA mutations, regimens using platinum and poly (ADP-ribose) polymerase inhibitor have recently been studied for their effectiveness. To date, the concept of FPC has prevailed in Western countries, and it has begun to infiltrate into Eastern countries. As the genetic background and environmental conditions vary in association with ethnicity and living area, we need to establish our own FPC registries and accumulate data in Asian countries.
Asian Continental Ancestry Group ; Drug Therapy ; Genetic Background ; Humans ; Pancreatic Neoplasms ; Platinum ; Registries ; Risk Factors

Pancreatic cancer is a dismal disease with a poor prognosis and is one of the most painful malignancies. Therefore, adequate pain control is essential to improving the patient's quality of life. Pain in pancreatic cancer has complex pathophysiologic mechanisms and different characteristics. The choice of pain management modalities should be individualized depending on the pain characteristics using a multidisciplinary approach. The treatment options available include medical treatment, chemotherapy, celiac plexus/ganglion neurolysis, radiotherapy, and endoscopic technique. This review discusses the medical and interventional options, leading to optimal pain management in patients with pancreatic cancer.
Drug Therapy ; Humans ; Pain Management ; Pancreatic Neoplasms ; Prognosis ; Quality of Life ; Radiotherapy

Pancreatic cancer is a major cause of cancer-related mortality and morbidity, and its incidence is increasing as the population is aging. On the other hand, significant improvement in the prognosis has not occurred. The absence of early diagnosis means that many patients are diagnosed only when they develop symptoms, such as jaundice, due to a biliary obstruction. The role of endoscopy in multidisciplinary care for patients with pancreatic cancer continues to evolve. Controversy remains regarding the best preoperative biliary drainage in patients with surgically resectable pancreatic head cancer. In general, patients undergoing a surgical resection usually do not require preoperative biliary drainage unless they have cholangitis or receive neoadjuvant chemotherapy. If biliary drainage is performed prior to surgery, the patient's condition and a multidisciplinary approach should be considered. With the increasing life expectancy of patients with pancreatic cancer, the need for more long-time biliary drainage or pre-operative biliary drainage is also increasing. Strong evidence of endoscopic retrograde cholangiopancreatography (ERCP) as a first-line and essential treatment for biliary decompression has been provided. On the other hand, the use of endoscopic ultrasound-guided biliary drainage as well as percutaneous biliary drainage has been also recommended. During ERCP, self-expandable metal stent could be recommended instead of a plastic stent for the purpose of long stent patency and minimizing stent-induced complications. In this review, several points of view regarding the relief of obstruction in patients with pancreatic cancer, and optimal techniques are being discussed.
Aging ; Cholangiopancreatography, Endoscopic Retrograde ; Cholangitis ; Decompression ; Drainage ; Drug Therapy ; Early Diagnosis ; Endoscopy ; Hand ; Head and Neck Neoplasms ; Humans ; Incidence ; Jaundice ; Life Expectancy ; Mortality ; Pancreatic Neoplasms ; Plastics ; Prognosis ; Stents

A 58-year-old woman presented with right flank and back pain for one month. After undergoing an abdominal computed tomography (CT), she was referred to our hospital. The abdominal CT showed a hypodense pancreatic tail mass with multiple retroperitoneal lymph node metastases. Positron emission tomography-computed tomography (PET-CT) scan showed high 18F-FDG uptake in pancreatic tumor and enlarged lymph nodes. Endoscopic ultrasound fine needle aspiration (EUS-FNA) revealed adenocarcinoma, which stained strongly in hENT1 (human equilibrative nucleoside transporter 1) on immunohistochemistry. She received gemcitabine 1,000 mg/m² + nanoparticle albumin-bound paclitaxel 125 mg/m² as a palliative chemotherapy. Follow-up abdominal CT and PET-CT after 4 cycles of chemotherapy showed that both pancreatic mass and the metastatic retroperitoneal lymph nodes were nearly disappeared. We report a case of 58-year-old female with metastatic pancreatic cancer who had a dramatic response to palliative chemotherapy (gemcitabine plus nanoparticle albumin-bound paclitaxel).
Adenocarcinoma ; Albumin-Bound Paclitaxel ; Back Pain ; Biopsy, Fine-Needle ; Drug Therapy ; Electrons ; Female ; Fluorodeoxyglucose F18 ; Follow-Up Studies ; Humans ; Immunohistochemistry ; Lymph Nodes ; Middle Aged ; Nanoparticles ; Neoplasm Metastasis ; Nucleoside Transport Proteins ; Pancreatic Neoplasms ; Tail ; Tomography, X-Ray Computed ; Ultrasonography