Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 15 de 15
Filter
Add more filters










Publication year range
1.
J Appl Physiol (1985) ; 136(4): 949-953, 2024 Apr 01.
Article in English | MEDLINE | ID: mdl-38420678

ABSTRACT

Decompression sickness (DCS) is caused by gaseous nitrogen dissolved in tissues forming bubbles during decompression. To date, no method exists to identify nitrogen within tissues, but with advances in positron-emission tomography (PET) technology, it may be possible to track gaseous radionuclides into tissues. We aimed to develop a method to track nitrogen movement in vivo and under hyperbaric pressure that could then be used to further our understanding of DCS using nitrogen-13 (13N2). A single anesthetized female Sprague-Dawley rat was exposed to 625 kPa, composed of air, isoflurane, and 13N2 for 10 min. The PET scanner recorded 13N2 during the hyperbaric exposure with energy windows of 250-750 keV. The PET showed an increase in 13N2 concentration in the lung, heart, and abdominal regions, which all reached a plateau after ∼4 min. This showed that it is possible to gain noninvasive in vivo measurements of nitrogen kinetics through the body while at hyperbaric pressures. Tissue samples showed radioactivity above background levels in the blood, brain, liver, femur, and thigh muscle when assessed using a γ counter. The method can be used to evaluate an array of challenges to our understanding of decompression physiology by quantifying nitrogen load through γ counts of 13N2, and signal intensity of the PET. Further development of the method will improve the specificity of the measured outcomes, and enable it to be used with larger mammals, including humans.NEW & NOTEWORTHY This article describes a method for the in vivo quantification and tracking of nitrogen through the mammalian body whilst exposed to hyperbaric pressure. The method has the potential to further our understanding of decompression sickness, and quantitatively evaluate the effectiveness of both the treatment and prevention of decompression sickness.


Subject(s)
Decompression Sickness , Diving , Hyperbaric Oxygenation , Nitrogen Radioisotopes , Humans , Rats , Animals , Female , Nitrogen , Decompression Sickness/diagnostic imaging , Diving/physiology , Rats, Sprague-Dawley , Decompression/adverse effects , Gases , Hyperbaric Oxygenation/methods , Positron-Emission Tomography , Mammals
3.
PLoS One ; 19(1): e0294611, 2024.
Article in English | MEDLINE | ID: mdl-38252649

ABSTRACT

BACKGROUND: Breathing pure oxygen causes nitrogen washout from tissues, a method commonly deployed to prevent decompression sickness from hypobaric exposure. Theoretically prebreathing oxygen increases the capacity for nitrogen uptake and potentially limits supersaturation during dives of short duration. We aimed to use 13N2, a radioactive nitrogen isotope, to quantify tissue nitrogen following normobaric and hyperbaric exposures. METHODS: Twenty Sprague Dawley rats were divided in 4 conditions; normobaric prebreathe, normobaric control, hyperbaric prebreathe, hyperbaric control. Prebreathed rats breathed oxygen for 1 h prior to the experiment whilst controls breathed air. Normobaric rats breathed air containing 13N2 at 100 kPa for 30 min, whereas hyperbaric rats breathed 13N2 at 700 kPa before being decompressed and sedated using air-isoflurane (without 13N2 for a few minutes). After euthanization, blood, brain, liver, femur and thigh muscle were analyzed by gamma counting. RESULTS: At normobaria prebreathing oxygen resulted in higher absolute nitrogen counts in blood (p = .034), as well as higher normalized counts in both the liver and muscle (p = .034). However, following hyperbaric exposure no differences were observed between conditions for any organ (p>.344). Both bone and muscle showed higher normalized counts after hyperbaria compared to normobaria. CONCLUSIONS: Oxygen prebreathing caused nitrogen elimination in normobaria that led to a larger "sink" and uptake of 13N2. The lack of difference between conditions in hyperbaria could be due to the duration and depth of the dive mitigating the effect of prebreathing. In the hyperbaric conditions the lower counts were likely due to off-gassing of nitrogen during the sedation procedure, suggest a few minutes was enough to off-gas in rodents. The higher normalized counts under hyperbaria in bone and muscle likely relate to these tissues being slower to on and off-gas nitrogen. Future experiments could include shorter dives and euthanization while breathing 13N2 to prevent off-gassing.


Subject(s)
Gases , Oxygen , Rats , Animals , Rats, Sprague-Dawley , Muscles , Nitrogen
4.
Laryngoscope ; 134(3): 1299-1307, 2024 Mar.
Article in English | MEDLINE | ID: mdl-37668315

ABSTRACT

OBJECTIVE: With the shift toward utilization of sentinel lymph node biopsy (SLNB) in oral cavity cancer, improved techniques for intraoperative sentinel node identification are needed. This study investigates the feasibility of fluorescently labeled tilmanoscept in SLNB in an oral cancer rabbit model. METHODS: An animal study was designed using 21 healthy male New Zealand rabbits. Gallium-68-labeled tilmanocept labeled with IRDye800CW was injected submucosally into the buccal mucosa (n = 6) or lateral tongue (n = 7) followed by PET imaging. One hour after injection, SLNB was performed using fluorescence imaging followed by a bilateral neck dissection and sampling of non-nodal surrounding tissue. All tissues were measured for radioactivity and fluorescence. In addition, eight rabbits were injected with delayed SLNB performed 48 h after injection. RESULTS: Buccal injections all had ipsilateral SLN drainage and tongue injections exhibited 18.2% contralateral drainage. An average of 1.9 ± 1.0 SLN (range 1-5) were identified. In addition, an average of 16.9 ± 3.3 non-sentinel lymph nodes were removed per animal. SLNs had an average of 0.69 ± 0.60 percent-of-injected dose (%ID) compared with non-sentinel nodes with 0.012 ± 0.025 %ID and surrounding tissue with 0.0067 ± 0.015 %ID. There was 98.0% agreement between sentinel lymph nodes identified using fluorescence compared to radioactivity with Cohen's kappa coefficient of 0.879. In 48-h delayed SLNB, results were consistent with 97.8% agreement with radioactivity and Cohen's Kappa coefficient of 0.884. Fluorescence identified additional lymph nodes that were not identified by radioactivity, and with one false negative. CONCLUSION: Fluorescent-labeled Tc-99 m-tilmanocept represents a highly accurate adjunct to enhance SLNB for oral cavity cancer. LEVEL OF EVIDENCE: N/A Laryngoscope, 134:1299-1307, 2024.


Subject(s)
Mouth Neoplasms , Sentinel Lymph Node , Male , Animals , Rabbits , Sentinel Lymph Node Biopsy/methods , Lymph Nodes/pathology , Sentinel Lymph Node/diagnostic imaging , Sentinel Lymph Node/surgery , Sentinel Lymph Node/pathology , Mouth Neoplasms/diagnostic imaging , Mouth Neoplasms/surgery , Mouth Neoplasms/pathology
6.
Sci Rep ; 13(1): 22217, 2023 12 14.
Article in English | MEDLINE | ID: mdl-38097649

ABSTRACT

Osteoprotegerin (OPG) is a secreted cytokine that functions as a decoy receptor for receptor activator of nuclear factor kappa-B (RANK) ligand (RANKL). Anti-RANKL treatment for bone metastasis has been widely accepted for solid tumors. However, the mechanism of OPG-RANKL-RANK signaling in systemic colorectal cancer (CRC) metastasis remains unclear. In this study, we investigated the relevance and function of OPG expression in CRC liver metastasis. First, we performed in silico analysis using The Cancer Genome Atlas public database and found that lower OPG expression in CRC was associated with poor overall survival. Immunohistochemistry analyses using resected specimen from patients with CRC in our institute confirmed the result. Patient-matched primary CRC and liver metastases showed a significant downregulation of OPG expression in metastatic lesions. In CRC cell lines, OPG expression did not suppress cell proliferation and migration. However, OPG expression inhibited macrophage migration by suppressing the RANKL-RANK pathway. Moreover, in vivo mouse liver metastasis models showed that OPG expression in CRC cells suppressed liver metastases. In addition, treatment with an anti-RANKL neutralizing antibody also suppressed liver metastases. These results showed that downregulation of OPG expression in CRC cells promotes liver metastasis by activating tumor-associated macrophage, which can become a candidate for targeted therapy with anti-RANKL neutralizing antibody for CRC liver metastasis.


Subject(s)
Colorectal Neoplasms , Liver Neoplasms , Animals , Humans , Mice , Antibodies, Neutralizing/metabolism , Colorectal Neoplasms/genetics , Down-Regulation , Liver Neoplasms/genetics , Osteoprotegerin/genetics , Osteoprotegerin/metabolism , RANK Ligand/genetics , RANK Ligand/metabolism , Receptor Activator of Nuclear Factor-kappa B/genetics , Receptor Activator of Nuclear Factor-kappa B/metabolism , Tumor-Associated Macrophages/metabolism
7.
PLoS Pathog ; 19(9): e1011487, 2023 09.
Article in English | MEDLINE | ID: mdl-37747931

ABSTRACT

Select prion diseases are characterized by widespread cerebral plaque-like deposits of amyloid fibrils enriched in heparan sulfate (HS), a abundant extracellular matrix component. HS facilitates fibril formation in vitro, yet how HS impacts fibrillar plaque growth within the brain is unclear. Here we found that prion-bound HS chains are highly sulfated, and that the sulfation is essential for accelerating prion conversion in vitro. Using conditional knockout mice to deplete the HS sulfation enzyme, Ndst1 (N-deacetylase / N-sulfotransferase) from neurons or astrocytes, we investigated how reducing HS sulfation impacts survival and prion aggregate distribution during a prion infection. Neuronal Ndst1-depleted mice survived longer and showed fewer and smaller parenchymal plaques, shorter fibrils, and increased vascular amyloid, consistent with enhanced aggregate transit toward perivascular drainage channels. The prolonged survival was strain-dependent, affecting mice infected with extracellular, plaque-forming, but not membrane bound, prions. Live PET imaging revealed rapid clearance of recombinant prion protein monomers into the CSF of neuronal Ndst1- deficient mice, neuronal, further suggesting that HS sulfate groups hinder transit of extracellular prion protein monomers. Our results directly show how a host cofactor slows the spread of prion protein through the extracellular space and identify an enzyme to target to facilitate aggregate clearance.


Subject(s)
Neurons , Prion Diseases , Prions , Sulfotransferases , Animals , Mice , Heparitin Sulfate/metabolism , Mice, Knockout , Neurons/enzymology , Prion Diseases/metabolism , Prion Proteins/genetics , Prions/metabolism , Sulfotransferases/genetics , Sulfotransferases/metabolism
8.
Cancer Lett ; 522: 129-141, 2021 12 01.
Article in English | MEDLINE | ID: mdl-34543685

ABSTRACT

Mutations of KRAS gene are found in various types of cancer, including colorectal cancer (CRC). Despite intense efforts, no pharmacological approaches are expected to be effective against KRAS-mutant cancers. Macropinocytosis is an evolutionarily conserved actin-dependent endocytic process that internalizes extracellular fluids into large vesicles called macropinosomes. Recent studies have revealed macropinocytosis's important role in metabolic adaptation to nutrient stress in cancer cells harboring KRAS mutations. Here we showed that KRAS-mutant CRC cells enhanced macropinocytosis for tumor growth under nutrient-depleted conditions. We also demonstrated that activation of Rac1 and phosphoinositide 3-kinase were involved in macropinocytosis of KRAS-mutant CRC cells. Furthermore, we found that macropinocytosis was closely correlated with asparagine metabolism. In KRAS-mutant CRC cells engineered with knockdown of asparagine synthetase, macropinocytosis was accelerated under glutamine-depleted condition, and albumin addition could restore the glutamine depletion-induced growth suppression by recovering the intracellular asparagine level. Finally, we discovered that the combination of macropinocytosis inhibition and asparagine depletion dramatically suppressed the tumor growth of KRAS-mutant CRC cells in vivo. These results indicate that dual blockade of macropinocytosis and asparagine bioavailability could be a novel therapeutic strategy for KRAS-mutant cancers.


Subject(s)
Aspartate-Ammonia Ligase/genetics , Colorectal Neoplasms/therapy , Pinocytosis/genetics , Proto-Oncogene Proteins p21(ras)/genetics , Asparagine/genetics , Asparagine/metabolism , Aspartate-Ammonia Ligase/antagonists & inhibitors , Cell Line, Tumor , Cell Proliferation/genetics , Colorectal Neoplasms/genetics , Colorectal Neoplasms/metabolism , Colorectal Neoplasms/pathology , Gene Knockdown Techniques , Humans , Mutation/genetics , Phosphatidylinositol 3-Kinases/genetics , rac1 GTP-Binding Protein/genetics
9.
Cancer Lett ; 487: 53-62, 2020 09 01.
Article in English | MEDLINE | ID: mdl-32473241

ABSTRACT

Tumor-stromal interaction is implicated in tumor progression. Although CCR1 expression in myeloid cells could be associated with pro-tumor activity, it remains elusive whether disruption of CCR1-mediated myeloid cell accumulation can suppress tumor progression. Here, we investigated the role of CCR1 depletion in myeloid cells in two syngeneic colorectal cancer mouse models: MC38, a transplanted tumor model and CMT93, a liver metastasis model. Both cells induced tumor accumulation of CCR1+ myeloid cells that express MMP2, MMP9, iNOS, and VEGF. Lack of the Ccr1 gene in host mice dramatically reduced MC38 tumor growth as well as CMT93 liver metastasis. To delineate the contribution of CCR1+ myeloid cells, we performed bone marrow (BM) transfer experiments in which sub-lethally irradiated wild-type mice were reconstituted with BM from either wild-type or Ccr1-/- mice. Mice reconstituted with Ccr1-/- BM exhibited marked suppression of MC38 tumor growth and CMT93 liver metastasis, compared with control mice. Consistent with these results, administration of a neutralizing anti-CCR1 monoclonal antibody, KM5908, significantly suppressed MC38 tumor growth and CMT93 liver metastases. Our findings highlight the importance of the application of CCR1 blockade as a therapeutic strategy.


Subject(s)
Cell- and Tissue-Based Therapy , Colorectal Neoplasms/genetics , Liver Neoplasms/genetics , Protein Serine-Threonine Kinases/genetics , Animals , Bone Marrow/metabolism , Bone Marrow/pathology , Cell Line, Tumor , Colorectal Neoplasms/pathology , Colorectal Neoplasms/therapy , Disease Models, Animal , Disease Progression , Gene Expression Regulation, Neoplastic/genetics , Heterografts , Humans , Liver Neoplasms/pathology , Liver Neoplasms/secondary , Liver Neoplasms/therapy , Matrix Metalloproteinase 2/genetics , Matrix Metalloproteinase 9/genetics , Mice , Myeloid Cells/metabolism , Myeloid Cells/pathology , Neoplasm Metastasis , Nitric Oxide Synthase Type II/genetics , Protein Serine-Threonine Kinases/therapeutic use , Vascular Endothelial Growth Factor A/genetics
10.
Cell Death Dis ; 10(4): 264, 2019 03 19.
Article in English | MEDLINE | ID: mdl-30890699

ABSTRACT

Mesenchymal stem cells (MSCs) are recruited from BM to the stroma of developing tumors, where they serve as critical components of the tumor microenvironment by secreting growth factors, cytokines, and chemokines. The role of MSCs in colorectal cancer (CRC) progression was controversial. In this study, we found that C-C chemokine receptor type 5 (CCR5) ligands (i.e., C-C motif chemokine ligand 3 (CCL3), CCL4, and CCL5) were highly produced from MSCs using a chemokine array screening with conditioned media from the cultured human MSCs. A relatively strong CCR5 expression could be detected within the cytoplasm of several CRC cell lines. Regarding the effect of MSC, we found that the xenografts in which CCR5-overexpressing HCT116 cells were inoculated into immunocompromised mice were highly promoted in vivo by a mixture with MSCs. Notably, the CCR5 inhibitor, maraviroc, significantly abolished the MSC-induced tumor growth in vivo. In human clinical specimens (n = 89), 20 cases (29%) were high for CCR5, whereas 69 cases (71%) were low. Statistical analyses indicated that CCR5 expression in primary CRC was associated with CRC patients' prognosis. Especially, stage III/IV patients with CCR5-high CRCs exhibited a significantly poorer prognosis than those with CCR5-low CRCs. Furthermore, we investigated the effects of preoperative serum CCR5 ligands on patients' prognosis (n = 114), and found that CRC patients with high serum levels of CCL3 and CCL4 exhibited a poorer prognosis compared to those with low levels of CCL3 and CCL4, while there was no association between CCL5 and prognosis. These results suggest that the inhibition of MSC-CRC interaction by a CCR5 inhibitor could provide the possibility of a novel therapeutic strategy for CRC, and that serum levels of CCL3 and CCL4 could be predictive biomarkers for the prognosis of CRC patients.


Subject(s)
Chemokine CCL3/metabolism , Chemokine CCL4/metabolism , Colorectal Neoplasms/metabolism , Mesenchymal Stem Cells/metabolism , Receptors, CCR5/metabolism , Aged , Animals , Bone Marrow/metabolism , Chemokine CCL3/blood , Chemokine CCL4/blood , Chemokine CCL5/blood , Chemokine CCL5/metabolism , Colonic Neoplasms/genetics , Colonic Neoplasms/metabolism , Colonic Neoplasms/pathology , Colorectal Neoplasms/genetics , Colorectal Neoplasms/pathology , Culture Media, Conditioned , Disease Progression , Female , HCT116 Cells , HT29 Cells , Humans , Mice , Mice, Nude , Prognosis , Receptors, CCR5/blood , Receptors, CCR5/genetics , Signal Transduction/genetics , Transplantation, Heterologous
11.
Clin Cancer Res ; 25(9): 2887-2899, 2019 05 01.
Article in English | MEDLINE | ID: mdl-30705034

ABSTRACT

PURPOSE: SMAD4 is a key transcriptional factor of TGFß signaling and acts as a tumor suppressor in colorectal cancer. In the present study, we explored the immunologic effect of SMAD4 on the tumor microenvironment. EXPERIMENTAL DESIGN: Using 99 clinical specimens and human colorectal cancer cell lines, we investigate the relationship between SMAD4 expression and neutrophil accumulation. We immunohistochemically analyzed expression of SMAD4, CXCL1, CXCL8, CXCR2, and other proteins with clinical specimens. Finally, we determined the serum levels of CXCL1 and CXCL8 in 125 patients with colorectal cancer. RESULTS: SMAD4 knockdown from human colorectal cancer cells upregulated the expression of CXCL1 and CXCL8, which recruited neutrophils to colorectal cancer tumor via CXCR2. In turn, when neutrophils were exposed to the supernatant of SMAD4-negative colorectal cancer cells, they produced a large amount of CXCL1 and CXCL8 by themselves in vitro. In human clinical specimens, we found that neutrophil infiltration into the peritumoral stroma was more marked in SMAD4-negative colorectal cancer compared with that in SMAD4-positive colorectal cancer, and that both CXCL1 and CXCL8 were abundantly expressed in the tumor-infiltrating neutrophils. Neutrophils isolated from primary colorectal cancer expressed significantly higher levels of CXCL1 and CXCL8 than did those isolated from peripheral blood. Furthermore, tumor-infiltrating neutrophils expressed MMP2 and MMP9 in addition to ARG1 and IDO. Serum CXCL8 level was significantly higher in colorectal cancer patients, especially those at stage II/III, and statistical analysis indicated a high CXCL8 level was associated with a shorter overall survival and relapse-free survival. CONCLUSIONS: Blockade of the CXCL1/8-CXCR2 axis could be a novel therapeutic approach against SMAD4-negative colorectal cancer.


Subject(s)
Biomarkers, Tumor/metabolism , Chemokine CXCL1/metabolism , Colorectal Neoplasms/pathology , Interleukin-8/metabolism , Neutrophils/pathology , Receptors, Interleukin-8B/metabolism , Smad4 Protein/metabolism , Apoptosis , Biomarkers, Tumor/genetics , Case-Control Studies , Cell Movement , Cell Proliferation , Chemokine CXCL1/genetics , Colorectal Neoplasms/genetics , Colorectal Neoplasms/metabolism , Disease Progression , Follow-Up Studies , Gene Expression Regulation, Neoplastic , Humans , Interleukin-8/genetics , Neutrophil Infiltration , Prognosis , Receptors, Interleukin-8B/genetics , Smad4 Protein/genetics , Survival Rate , Tumor Cells, Cultured , Tumor Microenvironment , Xenograft Model Antitumor Assays
12.
Int J Mol Sci ; 20(3)2019 Jan 27.
Article in English | MEDLINE | ID: mdl-30691207

ABSTRACT

Colorectal cancer (CRC) is one of the most common causes of cancer deaths worldwide and the number of CRC patients is increasing progressively. Despite the improvement of the surgical techniques and chemotherapy, we have not completely overcome this disease yet due to the metastases. Therefore, understanding the mechanisms through which metastasis occurs is important for overcoming CRC. Normal host cells in the tumor microenvironment, such as macrophages and fibroblasts, have been reported to promote the growth of CRCs. Although neutrophils were originally considered to have defensive functions against tumor cells, it has been revealed that some populations of neutrophils, called as tumor-associated neutrophils (TANs), have tumor-supportive functions. The plasticity between tumor-suppressive and -supportive neutrophils are regulated by transforming growth factor (TGF)-ß and Interferon-ß signaling. Some studies have demonstrated that TANs promote the spread of cancer cells to distant organs. TANs contribute to the tumor invasion and angiogenesis through the production of matrix metalloproteinase-9 (MMP9), vascular endothelial growth factor (VEGF), and hepatocyte growth factor (HGF) in the primary and metastatic sites. Neutrophils also promotes tumor cell dissemination by capturing circulating tumor cells using neutrophil extracellular traps and promote their migration to distant sites. The neutrophil-to-lymphocyte ratio is a well-defined predictive marker for CRC patients. In this review, we highlight the molecular signaling between TANs and CRC cells and the possibility of TANs as a potential target for cancer therapy.


Subject(s)
Colorectal Neoplasms/pathology , Interferon-beta/metabolism , Neutrophils/pathology , Transforming Growth Factor beta/metabolism , Colorectal Neoplasms/immunology , Hepatocyte Growth Factor/metabolism , Humans , Matrix Metalloproteinase 9/metabolism , Neoplasm Invasiveness , Neutrophils/immunology , Signal Transduction , Tumor Microenvironment , Vascular Endothelial Growth Factor A/metabolism
13.
Asian J Endosc Surg ; 10(1): 51-54, 2017 Feb.
Article in English | MEDLINE | ID: mdl-27593523

ABSTRACT

A solitary fibrous tumor is a ubiquitous mesenchymal fibroblastic tumor that was previously considered limited to the pleural cavity. Here, we report a rare case of a large solitary fibrous tumor of the mesorectum, which was successfully resected laparoscopically. A 56-year-old woman was referred to our hospital for a giant pelvic mass. Pelvic MRI showed a well-circumscribed mass, 12 cm in diameter, with heterogeneous signal intensity on T2 -weighted images. It was diagnosed as a benign mesorectal tumor of unknown origin. We successfully resected the entire tumor laparoscopically. Histological examination revealed it to be an extrapleural solitary fibrous tumor. For large tumors in the pelvis, the laparoscopic approach is preferable in terms of intraoperative hemorrhage, as long as they do not invade surrounding tissues.


Subject(s)
Laparoscopy , Rectal Neoplasms/surgery , Rectum/surgery , Solitary Fibrous Tumors/surgery , Female , Humans , Middle Aged
14.
Int J Mol Sci ; 17(5)2016 Apr 28.
Article in English | MEDLINE | ID: mdl-27136535

ABSTRACT

Colorectal cancer (CRC) is one of the leading causes of cancer-related death worldwide. Although most of the primary CRC can be removed by surgical resection, advanced tumors sometimes show recurrences in distant organs such as the liver, lung, lymph node, bone or peritoneum even after complete resection of the primary tumors. In these advanced and metastatic CRC, it is the tumor-stroma interaction in the tumor microenvironment that often promotes cancer invasion and/or metastasis through chemokine signaling. The tumor microenvironment contains numerous host cells that may suppress or promote cancer aggressiveness. Several types of host-derived myeloid cells reside in the tumor microenvironment, and the recruitment of them is under the control of chemokine signaling. In this review, we focus on the functions of chemokine signaling that may affect tumor immunity by recruiting several types of bone marrow-derived cells (BMDC) to the tumor microenvironment of CRC.


Subject(s)
Chemokines/metabolism , Colorectal Neoplasms/pathology , Bone Marrow Cells/cytology , Bone Marrow Cells/metabolism , Colorectal Neoplasms/metabolism , Humans , Neoplasm Metastasis , Neoplasm Recurrence, Local , Tumor Microenvironment
15.
World J Surg Oncol ; 14: 56, 2016 Feb 25.
Article in English | MEDLINE | ID: mdl-26911142

ABSTRACT

BACKGROUND: This study sought to clarify the clinical benefits of liver resection after downsizing systemic chemotherapy for initially unresectable colorectal liver metastases (CLM). METHODS: Survival and clinical characteristics of CLM patients who underwent resection between January 2001 and December 2013 were retrospectively assessed. The study cohort of 88 patients with limited liver disease who underwent curative liver resection comprised 34 with initially resectable synchronous disease (synchronous group), 38 with initially resectable metachronous disease (metachronous group), and 16 with initially unresectable converted disease (conversion group). RESULTS: The median duration of follow-up for the overall study population was 33 (1-98) months. Overall survival (OS) in the conversion group was not significantly different from that in the other groups. However, disease-free survival (DFS) in the conversion group was significantly shorter than that in the synchronous group. The median DFS was 19.1 months in the synchronous group, 16.6 months in the metachronous group, and 15.3 months in the conversion group. Most patients in the conversion group had recurrence shortly after liver resection in the remnant liver with or without metastases at other sites, but many could undergo repeat hepatectomy or resection of the metastases at other sites. CONCLUSIONS: Although the converted patients tended to have recurrence shortly after liver resection, survival could be prolonged by repeat hepatectomy or resection of metastases at other sites. Liver resection after downsizing chemotherapy appears to be efficacious for patients with initially unresectable CLM and may result in long-term outcomes equivalent to those of patients with initially resectable CLM.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Colorectal Neoplasms/surgery , Hepatectomy , Liver Neoplasms/surgery , Neoplasm Recurrence, Local/surgery , Adult , Aged , Aged, 80 and over , Chemotherapy, Adjuvant , Colorectal Neoplasms/drug therapy , Colorectal Neoplasms/pathology , Combined Modality Therapy , Female , Follow-Up Studies , Humans , Liver Neoplasms/drug therapy , Liver Neoplasms/secondary , Male , Middle Aged , Neoplasm Recurrence, Local/drug therapy , Neoplasm Recurrence, Local/pathology , Neoplasm Staging , Prognosis , Prospective Studies , Retrospective Studies , Survival Rate
SELECTION OF CITATIONS
SEARCH DETAIL
...