ABSTRACT
BACKGROUND: Hemothorax occurs in approx. 0.4% of all chest injury patients, but hemothorax due to a thoracic vertebral fracture is rare. CASE PRESENTATION: A 76-year-old Japanese man was transported to our hospital for right hemothorax due to a car accident. We performed emergency hemostasis surgery and tried to stop the bleeding by several methods, but it was difficult to control the bleeding because the bleeding point was an artery branch that runs in front of the vertebral body. CONCLUSION: It is important to be aware that a fractured vertebra can damage the aorta's arterial branch and follow a severe course.
ABSTRACT
BACKGROUND/AIM: Additional primary malignancy (APM) risk is increasing with improved prognosis of cancer survivors. In order to clarify risk factors and patients susceptible to develop APMs, we investigated the clinical features, prognosis, and approaches for diagnosis and treatment in these patients. PATIENTS AND METHODS: Among 874 patients newly diagnosed with gastrointestinal tract (GIT) or hepato-biliary-pancreatic (HBP) cancers between 2011 and 2014, 124 with a synchronous and/or metachronous APM were identified. Patient characteristics, time interval between the malignancies, clue to detect APMs, treatment approaches, and prognosis were investigated. RESULTS: Patients with APMs were older and predominantly male. Half of the metachronous APMs were detected within 3 years after the first primary malignancy (PM). The main clue to detect synchronous and metachronous APMs was preoperative screening for current PM, and follow-up of prior PM, respectively. There was no significant difference in the overall survival between colon cancer patients with or without APMs. CONCLUSION: Multiple PMs were present in 14.2% of patients. Male and old age were identified to be risk factors for APM. Pre-operative screening and post-operative regular follow-ups are important for detecting synchronous or metachronous APMs.
Subject(s)
Digestive System Neoplasms/diagnosis , Digestive System Neoplasms/surgery , Neoplasms, Multiple Primary/diagnosis , Neoplasms, Multiple Primary/surgery , Age Factors , Aged , Aged, 80 and over , Digestive System Neoplasms/pathology , Early Detection of Cancer , Female , Humans , Male , Neoplasms, Multiple Primary/pathology , Prognosis , Survival AnalysisABSTRACT
Pancreatic ductal adenocarcinoma (PDAC) is among the most deadly types of malignancies because of its high ability to metastasize. PDAC is thought to be under hypoxic condition. Therefore, to investigate the mechanism of metastatic processes, chronic-hypoxia-resistant PDAC cells were newly generated under hypoxic condition for 3-6 months and reoxygenation experiments were performed using these chronic-hypoxia-resistant PDAC cells in in vivo-mimicking conditions. Proliferation, invasiveness and tumorigenicity in PDAC cells were significantly increased by reoxygenation. A Hedgehog (Hh) signaling component, Gli1, was significantly increased by reoxygenation. Gli1 knockdown inhibited reoxygenation-induced increases in proliferation and tumorigenicity and decreased invasiveness through suppression of matrix metalloproteinase (MMP) 2 and MMP9. Moreover, inhibition of Sonic Hh and Smoothened abrogated reoxygenation induced increases in proliferation and invasiveness. These results suggest that metastatic processes in PDAC are induced through activation of the Hh signaling pathway. Therefore, the Hh signaling pathway may be a therapeutic target for refractory PDAC in metastatic processes induced by reoxygenation.
Subject(s)
Carcinoma, Pancreatic Ductal/metabolism , Oxygen/metabolism , Pancreatic Neoplasms/metabolism , Signal Transduction , Animals , Carcinoma, Pancreatic Ductal/secondary , Cell Hypoxia , Cell Line, Tumor , Female , Hedgehog Proteins/metabolism , Humans , Matrix Metalloproteinase 2/metabolism , Matrix Metalloproteinase 9/metabolism , Mice , Mice, Inbred BALB C , Mice, Nude , Pancreatic Neoplasms/pathology , Receptors, G-Protein-Coupled/metabolism , Smoothened Receptor , Transcription Factors/metabolism , Zinc Finger Protein GLI1ABSTRACT
Pancreatic cancer is one of the deadliest types of cancer. Previously, we showed that hypoxia increases invasiveness through upregulation of Smoothened (Smo) transcription in pancreatic ductal adenocarcinoma (PDAC) cells. Here, we first evaluated whether hypoxia-induced increase in Smo contributes to the proliferation of PDAC cells. We showed that Smo, but not Gli1, inhibition decreases proliferation significantly under hypoxic conditions. To further investigate the effects of Smo on PDAC growth, cell cycle analysis was carried out. Inhibition of Smo under hypoxia led to G(0) /G(1) arrest and decreased S phase. As 5-fluorouracil (5-FU) and gemcitabine, which are first-line drugs for pancreatic cancer, are sensitive to S phase, we then evaluated whether cyclopamine-induced decreased S phase under hypoxia affected the chemosensitivity of 5-FU and gemcitabine in PDAC cells. Cyclopamine treatment under hypoxia significantly decreased chemosensitivity to 5-FU and gemcitabine under hypoxia in both in vitro and in vivo models. In contrast, cis-diamminedichloroplatinum, which is cell cycle-independent, showed significant synergistic effects. These results suggest that hypoxia-induced increase of Smo directly contributes to the proliferation of PDAC cells through a hedgehog/Gli1-independent pathway, and that decreased S phase due to the use of Smo inhibitor under hypoxia leads to chemoresistance in S phase-sensitive anticancer drugs. Our results could be very important clinically because a clinical trial using Smo inhibitors and chemotherapy drugs will begin in the near future.
Subject(s)
Deoxycytidine/analogs & derivatives , Fluorouracil/pharmacology , Hedgehog Proteins/antagonists & inhibitors , Pancreatic Neoplasms/drug therapy , Veratrum Alkaloids/pharmacology , Animals , Antimetabolites, Antineoplastic/pharmacology , Apoptosis/drug effects , Cell Cycle Checkpoints/drug effects , Cell Hypoxia , Cell Line, Tumor , Cell Proliferation/drug effects , Deoxycytidine/pharmacology , Female , Flow Cytometry , Hedgehog Proteins/metabolism , Humans , Immunoblotting , Mice , Mice, Inbred BALB C , Mice, Nude , Pancreatic Neoplasms/metabolism , Pancreatic Neoplasms/pathology , RNA Interference , Receptors, G-Protein-Coupled/genetics , Receptors, G-Protein-Coupled/metabolism , Smoothened Receptor , Transcription Factors/genetics , Transcription Factors/metabolism , Xenograft Model Antitumor Assays , Zinc Finger Protein GLI1 , GemcitabineABSTRACT
The hedgehog (Hh) signaling pathway is activated in various types of cancer including pancreatic ductal adenocarcinoma. It has been shown that extremely low oxygen tension (below 1% O2) is found in tumor tissue including pancreatic ductal adenocarcinoma cells (PDAC) and increases the invasiveness of PDAC. To investigate the contribution of the Hh pathway to hypoxia-induced invasiveness, we examined how hypoxia affects Hh pathway activation and the invasiveness of PDAC. In the present study, three human PDAC lines were cultured under normoxic (20% O2) or hypoxic (1% O2) conditions. Hypoxia upregulated the transcription of Sonic hedgehog (Shh), Smoothened (Smo), Gli1 and matrix metalloproteinase9 (MMP9) and increased the invasiveness of PDAC. Significantly, neither the addition of recombinant Shh (rhShh) nor the silencing of Shh affected the transcription of these genes and the invasiveness of PDAC. On the other hand, silencing of Smo decreased the transcription of Gli1 and MMP9 and PDAC invasiveness. Silencing of Gli1 or MMP9 decreased PDAC invasiveness. These results suggest that hypoxia activates the Hh pathway of PDAC by increasing the transcription of Smo in a ligand-independent manner and increases PDAC invasiveness.
