Ya Hu

Primary pancreatic lymphoma: a clinical quandary of diagnosis and treatment.

Objective: To investigate the clinical feature and treatment strategy of primary pancreatic lymphoma. Methods: Thirty-nine cases of primary pancreatic lymphoma reported in China were reviewed retrospectively with their clinical characters, treatment, and outcome, as well as a literature review of worldwide reports. Results: The major clinical presentations included discomfort or pain in the upper abdomen and jaundice without specificity. Only 2 cases were identified correctly by computed tomography, and 5 cases obtained a positive finding in a biopsy before operation. Thirty-two patients accepted operation; 13 pancreatoduodenectomy and 6 distal pancreatectomy were performed. Thirty-one patients accepted postoperative chemotherapy. Until now, 26 patients are still alive at a range of 3 to 72 months; 5 patients died at 5 to 24 months after operation. Literature review revealed 85 additional cases of pancreatic lymphoma in English reports. Their diagnosis and treatment methods varied. Conclusions: Primary pancreatic lymphoma was misdiagnosed as pancreatic adenocarcinoma frequently. Fine needle aspiration biopsy is the most valuable method in preoperative diagnosis. The cyclophosphamide, doxorubicin, vincristine, and prednisone scheme was still the most commonly used regimen of chemotherapy. The value of surgery and radiotherapy remains controversial; an operation combining chemotherapy seems to be an appropriate method of treatment for a patient in whom malignancy cannot be ruled out.

The underlying mechanisms of non-coding RNAs in the chemoresistance of pancreatic cancer.

Pancreatic cancer, which is often asymptomatic, is currently one of the most common causes of cancer-related death. This phenomenon is most likely due to a lack of early diagnosis, a high metastasis rate and a disappointing chemotherapy outcome. Thus, improving treatment outcomes by overcoming chemotherapy resistance may be a useful strategy in pancreatic cancer. Various underlying mechanisms involved in the chemoresistance of pancreatic cancer have been investigated. Notably, non-coding RNAs (ncRNAs), especially microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), play a pivotal role in regulating sensitivity to chemotherapy in pancreatic cancer. In this review, we highlight recent evidence regarding the role of miRNAs and lncRNAs in the chemoresistance of pancreatic cancer, including their expression levels, targets, biological functions and the regulation of chemoresistance, and discuss the potential clinical application of miRNAs and lncRNAs in the treatment of pancreatic cancer.

Paraganglioma of the pancreas: a potentially functional and malignant tumor.

Paragangliomas are neoplasms that arise from extra-adrenal chromaffin cells. Pancreatic paragangliomas are rare, and few are malignant. To the best of our knowledge, no cases of functional pancreatic paragangliomas have been reported in the literature to date. We present two cases of pancreatic paragangliomas with pathological confirmation. In the case 1, clinical testing and pathological analysis revealed functional and malignant characteristics of the tumor, which carried a poor prognosis. In case 2, functional paraganglioma was suspected. The clinical presentations and outcomes of these two patients are summarized, and the relevant literature is reviewed. Because of the small number of cases reported previously, few characteristics of these tumors are known. The best methods of predicting the malignant and functional potential of these tumors remain unknown. We propose careful preoperative treatment and close postoperative follow-up of paraganglioma patients because of the functional and malignant potential of these tumors.

Human adipose-derived stromal/stem cells: A novel approach to inhibiting acute pancreatitis

Acute pancreatitis, a common necroinflammatory disease of the pancreas, remains an unsolved problem that is associated with significant morbidity and mortality. Intra-acinar cell activation of digestion enzymes triggers the events of acute pancreatitis and stimulates the production of inflammatory cytokines. Finally, inflammatory cytokines trigger inflammatory cascades that lead to systemic inflammatory response syndrome, multi-organ failure, or death. Therefore, proposing a novel strategy for acute pancreatitis would be greatly valuable. Research on adult stem cells has achieved a great deal of progress related to the repair and regeneration of tissues and organs. Human adipose-derived stromal/stem cells become a crucial model to study diseases and develop novel therapeutic applications, as these cells are plentiful, easier to obtain, and require less-invasive procedures. Accumulated data suggest human adipose-derived stromal/stem cells would be a valuable tool for cell-based therapy for inflammatory disease, autoimmune disease, tissue repair, and ischemic insults by controlling cell death, immune response, inflammation, and tissue regeneration. Thus, it is reasonable to hypothesize that human adipose-derived stromal/stem cells would be a novel approach to inhibiting inflammation and reducing acute pancreatitis.

Mortality Indicators and Risk Factors for Intra-Abdominal Hypertension in Severe Acute Pancreatitis

This study assessed the risk factors associated with mortality and the development of intra-abdominal hypertension (IAH) in patients with severe acute pancreatitis (SAP). To identify significant risk factors, we assessed the following variables in 102 patients with SAP: age, gender, etiology, serum amylase level, white blood cell (WBC) count, serum calcium level, Acute Physiology and Chronic Health Evaluation II (APACHE-II) score, computed tomography severity index (CTSI) score, pancreatic necrosis, surgical interventions, and multiple organ dysfunction syndrome (MODS). Statistically significant differences were identified using the Student t test and the χ (2) test. Independent risk factors for survival were analyzed by Cox proportional hazards regression. The following variables were significantly related to both mortality and IAH: WBC count, serum calcium level, serum amylase level, APACHE-II score, CTSI score, pancreatic necrosis, pancreatic necrosis >50%, and MODS. However, it was found that surgical intervention had no significant association with mortality. MODS and pancreatic necrosis >50% were found to be independent risk factors for survival in patients with SAP. Mortality and IAH from SAP were significantly related to WBC count, serum calcium level, serum amylase level, APACHE-II score, CTSI score, pancreatic necrosis, and MODS. However, Surgical intervention did not result in higher mortality. Moreover, MODS and pancreatic necrosis >50% predicted a worse prognosis in SAP patients.

Prognostic significance of SUVmax and serum carbohydrate antigen 19-9 in pancreatic cancer

AIM To investigate the prognostic significance of pretreatment standardized maximum uptake value (SUVmax) and serum carbohydrate antigen (CA)19-9 in pancreatic cancer. METHODS From January 2007 to October 2011, 80 consecutive patients with pancreatic cancer who received positron emission/computed tomography before any treatment were enrolled in this study. The pretreatment SUVmax and CA19-9 level of the primary pancreatic tumor were obtained and compared with clinicopathological and prognostic factors. Students t test for unpaired data was used to analyze the differences between two groups. Univariate analysis and Cox proportional hazards regression were used to examine the independent effects of each significant variable. Survival was analyzed by the Kaplan-Meier method. RESULTS There was a significant correlation between both the SUVmax and serum CA19-9 of pancreatic cancer and R0 surgical resection (P = 0.043 and P = 0.007). Lymph node metastasis was associated with SUVmax (P = 0.017), but not serum CA19-9 (P = 0.172). On the contrary, the tumor stage was significantly related to serum CA19-9 (P = 0.035), but not SUVmax (P = 0.110). The univariate analysis showed that survival time was significantly related to tumor stage (P < 0.001), lymph node metastasis (P = 0.043), R0 surgical resection (P < 0.001), serum CA19-9 (P = 0.001), SUVmax (P < 0.001) and SUVmax plus CA19-9 (P = 0.002). Multivariate analysis clearly showed that only tumor stage (hazard ratio = 0.452; P = 0.020) was an independent prognostic factor for overall survival in pancreatic cancer. Higher SUVmax or CA19-9 showed worse prognosis. We found that high serum CA19-9 plus SUVmax was the most significant variable. CONCLUSION Higher pretreatment SUVmax and serum CA19-9 indicates poor prognosis. SUVmax plus serum CA19-9 is the most significant variable in predicting survival.

MiR-10a-5p targets TFAP2C to promote gemcitabine resistance in pancreatic ductal adenocarcinoma

BackgroundBy regulating target genes, microRNAs play essential roles in carcinogenesis and drug resistance in human pancreatic ductal adenocarcinoma (PDAC). Previous studies have shown that microRNA-10a-5p (miR-10a-5p) is overexpressed in PDAC and acts as an oncogene to promote the metastatic behavior of PDAC cells. However, the role of miR-10a-5p in PDAC chemoresistance remains unclear.MethodsThe effects of miR-10a-5p on biological behaviors were analyzed. MiR-10a-5p and TFAP2C levels in tissues were detected, and the clinical value was evaluated.ResultsWe found that miR-10a-5p is up-regulated in gemcitabine-resistant PDAC cells and enhances PDAC cell gemcitabine resistance in vitro and vivo. Meanwhile, we also determined that miR-10a-5p promotes the migratory and invasive ability of PDAC cells. Next, we confirmed that transcription factor activating protein 2 gamma (TFAP2C) is a target of miR-10a-5p, and TFAP2C overexpression resensitizes PDAC cells to gemcitabine, which is initiated by miR-10a-5p. Further studies revealed that TFAP2C also decreased PDAC cell migration and invasion capability. Finally, survival analysis demonstrated that high miR-10a-5p expression levels and low TFAP2C expression levels were both independent adverse prognostic factors in patients with PDAC.ConclusionTogether, these results indicate that miR-10a-5p/TFAP2C may be new therapeutic target and prognostic marker in PDAC.

Pancreatic carcinosarcoma mimics malignant intraductal papillary mucinous neoplasm: A rare case report and literature review

Rationale: Carcinosarcoma, an extremely rare pancreatic primary tumor, is characterized by coexistence of both carcinomatous and sarcomatous components. Due to its rarity, the clinical manifestation and imaging features have not been recognized. An accurate diagnostic method has not been available and a widely accepted guidelines instructing treatment has not been established. Patient concerns: We present an uncommon case of pancreatic carcinosarcoma (PCS) which has been preoperatively diagnosed as pancreatic malignant intraductal papillary mucinous neoplasm. A radical resection, including total pancreatectomy (TP) and splenectomy, was performed. Diagnosis: The diagnosis of PCS was confirmed by postoperative pathology. Interventions: A radical resection, including TP and splenectomy, was performed. The patient was followed up by abdominal contrast-enhanced computed tomography scan and blood tumor marker examination. Outcomes: The patient is still alive and self-sufficient 7 months after the surgery. No evidence of tumor recurrence is found during follow-up. Lessons: Although, until recently, there are no widely accepted guidelines instructing treatment for PCS, a radical resection is still a possible way. All the pancreatic neoplastic patients with high surgical risk should be transferred to a specialized high-volume pancreatic center to get precise preoperative evaluation, fine operation technique, and careful postoperative management.

The Clinical Features of Cystic Parathyroid Adenoma in Chinese Population: A Single-Center Experience

Objective Cystic parathyroid adenoma is a rare cause of primary hyperparathyroidism, but its preoperative diagnosis and management remain inconclusive. Method We retrospectively identified patients with cystic parathyroid adenomas who underwent surgery at Peking Union Medical College Hospital. Results Patients with cystic parathyroid adenomas had higher serum intact parathyroid hormone and calcium levels, larger maximum tumor diameter, and lower serum inorganic phosphorus level than did those with solid adenomas. Patients with cystic adenomas were predominantly male, and hypercalcemic crisis and atypical adenomas were common. The accuracy of preoperative localization methodologies was lower in patients with cystic adenomas than in patients with solid adenomas. US-guided fine-needle aspiration was performed in 11 patients. In all patients, the iPTH level in cystic fluid was much higher than that in serum. No sign of recurrence was observed after a median follow-up of 39 months. Conclusions Cystic parathyroid adenomas may not be as rare as previously reported. FNA may be a safe and feasible localization methodology for patients with inconclusive preoperative localization methodologies. Close follow-up is necessary for patients with cystic parathyroid adenomas, which account for a substantial proportion of atypical adenoma cases.

Preliminary Exploration of Potential Molecular Therapeutic Targets in Recurrent and Metastatic Parathyroid Carcinomas: Preliminary Exploration of Potential Molecular Therapeutic Targets in Recurrent and Metastatic Parathyroid Carcinomas

Parathyroid carcinoma (PC) is a rare endocrine malignancy. Surgical resection is curative for local lesions, while effective therapies are lacking for recurrent or metastatic PCs. To study whether targeted therapies could be applied in recurrent or metastatic PCs, potential therapeutic targets were identified with next‐generation sequencing (NGS). DNA was extracted from formalin‐fixed, paraffin‐embedded (FFPE) sections from 19 recurrent or metastatic PC samples. A panel of 560 genes was sequenced with NGS to identify genomic alterations at an average sequencing depth of 581×. In total, 190 genomic alterations were identified. Nine PC samples (47%) harbored at least one potentially actionable genomic alteration including in the after genes: ROS1 (5/19; 26%), PTEN (3/19; 16%), TSC1 (2/19; 11%), PIK3CA (1/19; 5%), AKT1 (1/19; 5%), MTOR (1/19; 5%), ERBB2 (1/19; 5%), NTRK1 (1/19; 5%), IDH1 (1/19; 5%) and FGFR3 (1/19; 5%). CDC73 mutations were detected in 9/19 (47%) PC samples. Additional recurrent genomic alterations were identified in MSH2 (15/19; 79%), AR (9/19; 47%), BCR (8/19; 42%), SLC45A3 (6/19; 32%), MAGI1 (5/19; 26%), ZNF521 (4/19; 21%), KMT2C (4/19; 21%) and NOTCH4 (4/19; 21%). Our study identified a relatively high frequency of potentially actionable genomic alterations in PC patients in a Chinese population for the first time. A series of recurrent mutant genes was detected as well. Our study contributes to both the selection of novel targeted therapies for PC and further molecular understanding of this refractory malignancy.