Safety and feasibility of irreversible electroporation for the pancreatic head in a porcine model.

BACKGROUND: Irreversible electroporation (IRE) is a local non-thermal ablative technique which has been suggested as a potential cancer therapy. However, the specific anatomic characteristics of the pancreatic head make it challenging to perform any local ablation in this region. Therefore, the safety and feasibility of IRE in the pancreatic head region should be further explored. AIM: To evaluate the safety of IRE in pancreatic head region including its effects on pancreatic ducts, vessels, and adjacent gastrointestinal organs. METHODS: Eight landrace miniature pigs underwent IRE of pancreatic head tissue successfully, with a total of 16 lesions created. Laboratory testing including white blood cell (WBC) count and serum amylase before IRE with follow-up laboratory analysis and pathological examination at 1, 7, 14, and 28 d postablation were performed. RESULTS: All pigs tolerated the ablation procedure without serious perioperative complications. Transiently elevated WBC count and amylase were observed at 24 h post-IRE, suggesting an acute pancreatic tissue damage which was confirmed by pathological observations. Vascular endothelial cells and pancreatic duct epithelial cells in ablation zone were also positive in terminal deoxynucleotidyl transferase dUTP nick end labeling staining. There was extensive duodenum mucosa damage with local hemorrhage 24 h after ablation, while regeneration of new villous structures were observed at 7 and 28 d post-IRE. Masson's trichromatic staining showed that the extracellular matrix was still intact in vessels and pancreatic ducts, and even in the duodenum. CONCLUSION: IRE ablation to the pancreatic head may be safe and feasible without long-term damage to the surrounding vital structures. However, risks of stress injuries in acute phase should be taken into consideration to prevent severe perioperative complications.

Prognostic factors for patients with mass-forming intrahepatic cholangiocarcinoma: A case series of 68 patients.

BACKGROUND: Intrahepatic cholangiocarcinoma (ICC) is the second most common primary liver cancer in humans after hepatocellular carcinoma and a rare epithelial malignancy that results in a poor prognosis. According to the Liver Cancer Study Group of Japan classification, ICC can be divided into three types: Mass-forming (MF) type, periductal-infiltrating (PI) type, and intraductal-growth type. The MF type is the most common, accounting for 57.1-83.6% of ICCs. Nevertheless, little is known about the epidemiology and treatment of MF ICC. AIM: To examine the prognostic factors for patients with MF ICC. METHODS: We carried out a retrospective analysis of consecutive patients with MF ICC treated at the Faculty of Hepato-Pancreato-Biliary Surgery of Chinese PLA General Hospital between January 2008 and December 2018. According to the treatment received, the patients were divided into either a resection group or an exploration group. RESULTS: The pooled 1-, 3-, and 5-year survival rates in the 68 patients with MF ICC were 66.5%, 36.3%, and 9.3%, respectively. Univariate analysis revealed that surgical resection (P < 0.001), nodal metastasis (P < 0.001), tumor location (P = 0.039), vascular invasion (P < 0.001), ascites (P < 0.001), and differentiation (P = 0.009) were significantly associated with the prognosis and survival of MF ICC. Multivariate analysis revealed that ascites (hazard ratio [HR] = 5.6, 95% confidence interval [CI]: 1.6-18.9, P = 0.006) and vascular invasion (HR = 2.5, 95%CI: 1.0-6.1, P = 0.045) were independent risk factors for MF ICC. The pooled 1-, 3-, and 5-year survival rates in the 19 patients of the exploration group were 5.3%, 5.3%, and 0, respectively. Among the 49 patients who underwent surgical resection, the pooled 1-, 3-, and 5-year survival rates were 93.5%, 49.7%, and 14.4%, respectively. Univariate and multivariate analyses revealed that vascular invasion (HR = 3.1, 95%CI: 1.2-8.5, P = 0.024) and nodal metastasis (HR = 3.2, 95%CI: 1.4-7.6, P = 0.008) were independent prognostic risk factors for surgical resection patients. CONCLUSION: The prognosis of MF ICC patients is dismal, especially those with ascites or vascular invasion. Surgical resection is a key factor in improving overall survival in patients with MF ICC, and vascular invasion and lymph node metastasis affect the efficacy of surgical resection.

Feasibility and safety of "bridging" pancreaticogastrostomy for pancreatic trauma in Landrace pigs.

BACKGROUND: In recent years, we created and employed a new anastomosis method, "bridging" pancreaticogastrostomy, to treat patients with extremely severe pancreatic injury. This surgery has advantages such as short length of surgery, low secondary trauma, rapid construction of shunts for pancreatic fluid, preventing second surgeries, and achieving good treatment outcomes in clinical practice. However, due to the limited number of clinical cases, there is a lack of strong evidence to support the feasibility and safety of this surgical procedure. Therefore, we carried out animal experiments to examine this procedure, which is reported here. AIM: To examine the feasibility and safety of a new rapid method of pancreaticogastrostomy, "bridging" pancreaticogastrostomy. METHODS: Ten Landrace pigs were randomized into the experimental and control groups, with five pigs in each group. "Bridging" pancreaticogastrostomy was performed in the experimental group, while routine mucosa-to-mucosa pancreaticogastrostomy was performed in the control group. After surgery, the general condition, amylase levels in drainage fluid on Days 1, 3, 5, and 7, fasting and 2-h postprandial blood glucose 6 mo after surgery, fasting, 2-h postprandial peripheral blood insulin, and portal vein blood insulin 6 mo after surgery were assessed. Resurgery was carried out at 1 and 6 mo after the former one to examine the condition of the abdominal cavity and firmness and tightness of the pancreaticogastric anastomosis and pancreas. RESULTS: After surgery, the general condition of the animals was good. One in the control group did not gain weight 6 mo after surgery, whereas significant weight gain was present in the others. There were significant differences on Days 1 and 3 after surgery between the two groups but no differences on Days 5 and 7. There were no differences in fasting and 2-h postprandial blood glucose and fasting and 2-h insulin values of postprandial peripheral blood and portal vein blood 6 mo after surgery between the two groups. One month after surgery, the sinus tract orifice/anastomosis was patent in the two groups. Six months after surgery, the sinus tract orifice/anastomosis was sealed, and pancreases in both groups presented with chronic pancreatitis. CONCLUSION: "Bridging" pancreaticogastrostomy is a feasible and safe a means of damage control surgery during the early stage of pancreatic injury.

Antibiotics and immunotherapy in gastrointestinal tumors: Friend or foe?

The incidence of gastrointestinal (GI) tumors is increasing year by year, and its pathogenesis is closely related to the intestinal flora. At present, the use of antibiotics is very common in the clinic. And cancer patients with low immunity are vulnerable to all sorts of infections, such as respiratory tract infections and urinary tract infections. Moreover, cancer patients easily run into fever and neutropenia induced by myelosuppression. Therefore, antibiotics are used extensively and even overused in many conditions. However, because of the special anatomical location of the gastrointestinal tract, the antibiotic usage will bring changes to the intestinal flora. Besides, with the expanding popularity of immunotherapy, various factors affecting the efficacy of immune checkpoint inhibitors (ICIs) have been extensively explored, including cancer-associated inflammation and the local and systemic factors that lead to immunosuppression. Some biomarkers for ICIs, including the expression of PD-L1, tumor mutation load, and microbiota, also have been investigated, and many studies have confirmed that gut microbiota can affect the efficacy of immunotherapy. But further studies on the influence of antibiotics directly on immunotherapy are rare. In this review, we discuss the relationship between GI tumors and antibiotics, the current status of immunotherapy in GI tumors, and the influence of antibiotics on immunotherapy.

Strepantibins A-C: Hexokinase II Inhibitors from a Mud Dauber Wasp Associated Streptomyces sp.

Two new p-terphenyls, strepantibins A and B (1 and 2), along with the first representative of a naturally occurring bisphenyltropone, strepantibin C (3), were characterized from a Streptomyces sp. associated with the larvae of the mud dauber wasp Sceliphron madraspatanum. Their structures were determined by high-resolution electrospray ionization mass spectrometry, NMR, and X-ray crystallography data interpretation. Strepantibins A-C inhibited hexokinase II (HK2) activity and displayed antiproliferative activity against hepatoma carcinoma cells HepG-2, SMMC-7721 and plc-prf-5. In SMMC-7721 cells treated with strepantibin A, the morphological characteristics of apoptosis were observed.

Effect of primary tumor side on survival outcomes in metastatic colorectal cancer patients after hepatic arterial infusion chemotherapy.

AIM: To analyze the survival data between patients diagnosed with right-sided primary (RSP) tumors and patients diagnosed with left-sided primary (LSP) tumors after hepatic arterial infusion chemotherapy (HAIC) at our center. METHODS: A retrospective analysis of pretreated metastatic colorectal cancer patients who received HAIC from May 2006 to August 2015 was conducted. A Cox proportional hazard regression analysis was used to assess the long-term survival outcomes. The mean and median age of patients was 61 years (range 27-85 years). There were 115 males and 53 females in our study. RESULTS: One hundred sixty-eight patients were enrolled in this study. The overall response rate was 28.9% in LSP patients and 27.3% in RSP patients. The disease control rate was 76.3% in LSP patients and 69.7% in RSP patients. The median overall survival in response to HAIC was 16.3 mo in the LSP arm and 9.3 mo in the RSP arm (P = 0.164). The median progression-free survival was 5.7 mo in the LSP arm and 4.2 mo in the RSP arm (P = 0.851). CONCLUSION: There was no significant difference in survival between LSP patients and RSP patients after HAIC. Further prospective studies are needed to confirm these findings.

Ivalin Inhibits Proliferation, Migration and Invasion by Suppressing Epithelial Mesenchymal Transition in Breast Cancer Cells.

Ivalin, an eudesmane-type sesquiterpene compound, was isolated from the Chinese herb Carpesium divaricatum in our chemistry group. In this study, we investigated the anti-migration and anti-invasion activities and underlying mechanisms of Ivalin in breast cancer cells in vitro. Cell viability was evaluated using the MTT assay, Western blotting was used to determine the expression of E-cadherin, N-cadherin, vimentin and ZEB1, and mRNA levels were analyzed by qPCR. The anti-migration and anti-invasion effects of Ivalin were measured by wound-healing and Transwell assays. In this connection, Ivalin treatment reduced the mRNA and protein expressions of ZEB1 as well as N-cadherin and vimentin expression in various breast cancer cells. E-cadherin expression was enhanced by Ivalin in the same cells, which implied that Ivalin depressed the process of epithelial-to-mesenchymal transition (EMT). Our results revealed that Ivalin significantly inhibited cell proliferation, migration and invasion in breast cancer cells in a dose-dependent manner in vitro. This study suggests that Ivalin may merit further investigation as a potential therapeutic leading compound for the treatment of breast cancer migration and invasion.

Hepatic artery infusion with raltitrexed or 5-fluorouracil for colorectal cancer liver metastasis.

AIM: To evaluate the efficiency and safety of hepatic artery infusion chemotherapy (HAIC) using raltitrexed or 5-fluorouracil for colorectal cancer (CRC) liver metastasis (CRCLM). METHODS: A retrospective analysis of patients with unresectable CRCLM who failed systemic chemotherapy and were subsequently treated with HAIC at our institute from May 2013 to April 2015 was performed. A total of 24 patients were treated with 5-fluorouracil, and 18 patients were treated with raltitrexed. RESULTS: The median survival time (MST) from diagnosis of CRC was 40.8 mo in the oxaliplatin plus raltitrexed (TOMOX) arm and 33.5 mo in the oxaliplatin plus 5-fluorouracil (FOLFOX) arm (P = 0.802). MST from first HAIC was 20.6 mo in the TOMOX arm and 15.4 mo in the FOLFOX arm (P = 0.734). Median progression-free survival (PFS) from first HAIC was 4.9 mo and 6.6 mo, respectively, in the TOMOX arm and FOLFOX arm (P = 0.215). Leukopenia (P = 0.026) was more common in the FOLFOX arm, and hepatic disorder (P = 0.039) was more common in the TOMOX arm. There were no treatment-related deaths in the TOMOX arm and one treatment-related death in the FOLFOX arm. Analysis of prognostic factors indicated that response to HAIC was a significant factor related to survival. CONCLUSION: No significant difference in survival was observed between the TOMOX and FOLFOX arms. HAIC treatment with either TOMOX or FOLFOX was demonstrated as an efficient and safe alternative choice.

Ectopic Cushing syndrome in small cell lung cancer: A case report and literature review.

Small cell lung cancer (SCLC) is a neuroendocrine tumor with the potential to secrete various peptides or hormones that can lead to paraneoplastic syndromes, such as Ectopic Cushing syndrome (ECS). Because of the aggressive nature of the syndrome and its atypical features, ECS in small-cell lung cancer is difficult to diagnose and has a poor prognosis. We report a case of a 74-year-old male patient who presented with severe hypokalemia, proximal muscle weakness, peripheral edema, metabolic alkalosis, and worsening hyperglycemia. The patient was eventually diagnosed with stage IV primary small-cell lung cancer and survived three months after diagnosis. We reviewed published articles to determine any new diagnostic techniques or advantages in the treatment regimen.

PCBP1 is an important mediator of TGF-ß-induced epithelial to mesenchymal transition in gall bladder cancer cell line GBC-SD.

Gall bladder carcinoma (GBC) is the seventh most common cancer across the globe and the most common malignancy of the biliary tract. Most GBC related deaths occur due to secondary progression and metastasis to distant organs. Epithelial-mesenchymal transition (EMT) is an important pre-requisite for tumor metastasis, however its mechanism in GBC has not yet been defined. Using the GBC-SD cell line, we have uncovered an important mediator, poly r(C) binding protein-1 (PCBP1), of transforming growth factor-beta (TGF-ß)-induced EMT in GBC. Our results show that TGF-ß treatment resulted in PCBP1 phosphorylation in accordance with similar observation in other model systems. We further showed through gain- and loss-of-function assays that PCBP1 expression levels regulate the capacity of GBC-SD cells to migrate and invade in vitro. Finally, our results showed that PCBP1 expression levels also regulate generation of CD44(+)CD24(-) progenitor cell population in GBC-SD cells after TGF-ß treatment. Cumulatively, our results indicate, pending further validation, that PCBP1 might be a prognostic marker for GBC metastasis.

The role of mitochondrial calcium uniporter in neuroprotection in traumatic brain injury.

The alteration in cellular Ca(2+) homeostasis is one of the key mechanisms contributing to secondary neuronal damage and altered physiology during the process of traumatic brain injury (TBI). However, there is considerable uncertainty about the efficacy of calcium channel blockers in randomized, controlled, clinical trials. In the physiological condition, cellular Ca(2+) homeostasis occurs through repetitive bursts of rising intracellular Ca(2+) that, sometimes are referred to as Ca(2+) oscillations. Mitochondria are intimately involved in the spatiotemporal tuning of cellular Ca(2+) signaling mainly through mitochondrial Ca(2+) uniporter (MCU). Excessive Ca(2+) uptake by the mitochondria through MCU is a key event in mitochondrial dysfunction and cell death in TBI. Selective inhibition of MCU has showed a promising cardioprotection and neuroprotection effect in many preclinical studies. Based on these preclinical results, the selective inhibition of MCU may be a new strategy for neuroprotection in TBI patients.