Junchao Guo

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.

Insights into the distinct roles of MMP-11 in tumor biology and future therapeutics (Review)

The biological processes of cancer cells such as tumorigenesis, proliferation, angiogenesis, apoptosis and invasion are greatly influenced by the surrounding microenvironment. The ability of solid malignant tumors to alter the microenvironment represents an important characteristic through which tumor cells are able to acquire specific functions necessary for their malignant biological behaviors. Matrix metalloproteinases (MMPs) are a family of zinc-dependent endopeptidases with the capacity of remodeling extracellular matrix (ECM) by degrading almost all ECM proteins, which plays essential roles during the invasion and metastasis process of solid malignant tumors, including allowing tumor cells to modify the ECM components and release cytokines, ultimately facilitating protease-dependent tumor progression. MMP-11, also named stromelysin-3, is a member of the stromelysin subgroup belonging to MMPs superfamily, which has been detected in cancer cells, stromal cells and adjacent microenvironment. Differently, MMP-11 exerts a dual effect on tumors. On the one hand MMP-11 promotes cancer development by inhibiting apoptosis as well as enhancing migration and invasion of cancer cells, on the other hand MMP-11 plays a negative role against cancer development via suppressing metastasis in animal models. Overexpression of MMP-11 was discovered in sera of cancer patients compared with normal control group as well as in multiple tumor tissue specimens, such as gastric cancer, breast cancer, and pancreatic cancer. At present, some evidence supports that MMP-11 may work as a significant tumor biomarker for early detection of cancer, tumor staging, prognostic analysis, monitoring recurrence during follow-up and also a potential target for immunotherapy against cancer. In view of the importance of MMP-11 in modifying tumor microenvironment and potent antitumoral effects on solid tumors, there is an urgent need for a deeper understanding of how MMP-11 modulates tumor progression, and exploring its potential clinical application.

Laparoscopic distal pancreatectomy with or without splenectomy: spleen-preservation does not increase morbidity.

BACKGROUND The indications for laparoscopic spleen-preserving distal pancreatectomy (LSPDP) and its morbidity compared with laparoscopic distal pancreatectomy with splenectomy (LDPS) are ill-defined. This study aimed to share the indications for spleen-preservation and investigate the safety and outcome of LSPDP at our institution. METHODS A retrospective review of patients who were scheduled to receive laparoscopic surgery for distal pancreatic lesions was conducted. The indications, surgical procedures, intra-operative data, and outcomes of the two procedures were collected and compared by statistical analysis. RESULTS LDPS and LSPDP were successfully performed in 16 and 21 patients respectively, whereas they were converted to open surgery in 9 patients. There were no significant differences in age, gender, operation time, blood loss, and conversion rate between the LDPS and LSPDP groups. The mean tumor size showed an inter-group difference (5.05 vs 2.53 cm, P<0.001). There were no significant differences in complication and morbidity rates between the two groups. All patients remained alive without recurrence during a follow-up of 9 to 67 months (median 35). CONCLUSION LSPDP has a morbidity and outcome comparable to LDPS.

Prognostic significance of epidermal growth factor-like domain 7 in pancreatic cancer

BACKGROUND Recent studies have shown the clinical significance of epidermal growth factor-like domain 7 (EGFL7) in a variety of cancers. However, the relationship between EGFL7 and the prognosis of pancreatic cancer (PC) remains unclear. The present study was undertaken to investigate the role of EGFL7 in the prognosis of PC. METHODS The expression of EGFL7 in nine PC cell lines was first determined by Western blotting analysis. Tissue microarray-based immunohistochemical staining was performed in paired formalin-fixed paraffin-embedded tumor and non-tumor samples from 83 patients with PC. Finally, correlations between EGFL7 expression and clinicopathological variables as well as overall survival were evaluated. RESULTS EGFL7 was widely expressed in all PC cell lines tested. EGFL7 expression in tumor tissues was significantly higher than that in non-tumor tissues (P=0.040). In addition, univariate analysis revealed that high EGFL7 expression in tumor tissues was significantly associated with poor overall survival, accompanied by several conventional clinicopathological variables, such as gender, histological grade and lymph node metastasis. In a multivariate Cox regression test, EGFL7 expression was identified as an independent marker for long-term outcome of PC. CONCLUSION Our data showed that EGFL7 is extensively expressed in PC and that EGFL7 is associated with poor prognosis.

CXCL12-CXCR7 axis contributes to the invasive phenotype of pancreatic cancer

Chemokine (C-X-C motif) receptor 7 (CXCR7) and its ligand, chemokine (C-X-C motif) ligand 12 (CXCL12), were established to be involved in biological behaviors and associated with prognosis in many cancers. However, effects, underlying mechanisms of CXCL12-CXCR7 axis in invasive phenotype of pancreatic cancer (PC) and its clinicopathologic significances have not been comprehensively explored. In the present study, it was first found by tissue microarray-based immunohistochemistry that CXCL12 and CXCR7 staining scores were significantly associated with vessel invasion and overall survival in two independent cohorts of PC. Besides, co-expression of these proteins was an independent prognosticator in multivariate analysis in both cohorts. Then, migration and invasion, but not proliferation, were decreased in CXCR7-stably silenced PC cells, whereas opposite changes were observed in CXCR7-stably overexpressed cells, accompanied by alterations of mTOR and Rho/ROCK pathways. CXCL12 stimulated migration, invasion, CXCR7 expression and phosphorylation of key mTOR proteins. AMD3100 did not influence effects of CXCL12. Two mTOR inhibitors, rapamycin and Torin1, reversed enhanced invasive phenotypes and mTOR phosphorylation in CXCR7-overexpressed cells. Moreover, CXCR7 directly interacts with mTOR. Finally, liver metastasis, but not growth, was affected by CXCR7 status in orthotopically-implanted PC models in nude mice. Collectively, CXCL12-CXCR7 axis accelerates migration and invasion of PC cells through mTOR and Rho/ROCK pathways, and predicts poor prognosis of PC.

Expression of c-fos was associated with clinicopathologic characteristics and prognosis in pancreatic cancer.

It has long been regarded that pancreatic cancer (PC) is a life-threatening malignant tumor. Thus, much attention has been paid for factors, especially relative molecules, predictive for prognosis of PC. However, c-fos expression in PC was less investigated. In addition, its association with clinicopathologic variables and prognosis remains unknown. In the present study, expression of c-fos was detected by tissue microarray-based immunohistochemical staining in cancer and adjacent tissues from 333 patients with PC. The staining results were correlated with clinicopathologic parameters and overall survival. Furthermore, prognostic significance of c-fos in subsets of PC was also evaluated. It was shown that low expression of c-fos was more often in cancer than in adjacent tissues of PC (P<0.001). Besides, high cancerous c-fos expression was significantly associated with tumor site and T stage, whereas peri-neural invasion was of a borderline significant relevance. Log-rank test revealed that high expression of c-fos in cancer tissues was a significant marker of poor overall survival, accompanied by some conventional clinicopathologic variables, such as sex, grade, peri-neural invasion, T and N stages. More importantly, cancerous c-fos expression was identified as an independent prognosticator in multivariate analysis. Finally, the prognostic implication of c-fos expression was proven in four subsets of patients with PC. These data suggested that c-fos expression was of relationships with progression and dismal prognosis of PC.

Activated mTOR/P70S6K signaling pathway is involved in insulinoma tumorigenesis

Insulinoma was a rare tumor and its pathogenesis was poorly understood. There had no study that focused on the role of mTOR signaling pathway in insulinoma tumorigenesis.

β1 and β3 integrins in breast, prostate and pancreatic cancer: A novel implication (Review)

Integrins are transmembrane glycoproteins that consist of an α and a β subunit. Specific integrin heterodimers preferentially bind to distinct extracellular matrix (ECM) proteins to affect the characteristics of cells or the components of the ECM. Among the different integrins, β1 and β3 integrins serve essential roles in the progression of different cancer-associated processes, including the initiation, proliferation, survival, migration and invasion. Furthermore, previous studies have revealed a ratio between these two integrins in cancer cells, which also demonstrated that the functions of these two integrins are paradoxical. This indicated that the proliferation and metastasis of cancer cells are not always parallel and may be considered independently maintained. Additionally, the present review may assist in understanding certain aspects of cancer, and in making clinical decisions in a novel and more comprehensive manner.

Splenic preservation in laparoscopic distal pancreatectomy.

Laparoscopic spleen‐preserving distal pancreatectomy (LSPDP) is designed principally for the removal of benign and low‐grade malignant lesions in the left pancreas. The aims of this study were to compare LSPDP with laparoscopic distal pancreatectomy with splenectomy (LDPS), compare two splenic preservation techniques (splenic vessel preservation and Warshaw technique) and investigate factors that influence splenic preservation.

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.