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1.
Gan To Kagaku Ryoho ; 51(2): 196-198, 2024 Feb.
Artículo en Japonés | MEDLINE | ID: mdl-38449411

RESUMEN

Radical cystectomy for locally advanced colorectal cancer with urinary bladder invasion significantly reduces the quality of life in exchange for a cure. We performed preoperative chemotherapy with FOLFOXIRI plus bevacizumab for 3 patients with locally advanced colorectal cancer with urinary bladder invasion to avoid radical cystectomy and to achieve local control for urinary bladder preservation. Grade 3 neutropenia was observed in 2 patients as an adverse reaction to the preoperative chemotherapy, but all 3 patients showed good tumor regression. All 3 patients underwent laparoscopic high anterior rectal resection and partial cystectomy, and all were able to undergo R0 resections with urinary bladder preservation. One patient had anastomotic leakage as a postoperative complication. One patient had local recurrence in the urinary bladder, and 2 had recurrence with peritoneal dissemination during their postoperative courses. Preoperative chemotherapy(FOLFOXIRI plus bevacizumab)for locally advanced colorectal cancer with urinary bladder invasion is considered to be a useful treatment option because of its potential for tumor shrinkage and bladder preservation.


Asunto(s)
Neoplasias Colorrectales , Neoplasias Primarias Secundarias , Neutropenia , Humanos , Vejiga Urinaria , Bevacizumab , Calidad de Vida , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/cirugía
2.
BMC Gastroenterol ; 23(1): 286, 2023 Aug 18.
Artículo en Inglés | MEDLINE | ID: mdl-37596515

RESUMEN

BACKGROUND: Malignant esophageal stenosis is a common and severe complication of advanced esophageal cancer that can be a serious problem in the continuation of chemotherapy and other anticancer treatments. The impact of chemotherapy regimens on the degree of improvement in esophageal stenosis is unknown. In this study, we focused on the impacts of chemotherapy on the direct anticancer effects, and in the improvement of malignant stenosis. METHODS: Patients who underwent radical esophagectomy after chemotherapy, either adjuvant 5-fluorouracil and cisplatin (FP) or docetaxel, cisplatin, and 5-fluorouracil (DCF) regimen, were included. We assessed the length of the cancerous stenosis, the width of the narrowest segment, and the size of the intraluminal area in the stenotic segment by fluoroscopy, and compared the differences before and after chemotherapy. In addition, we evaluated the dysphagia score (Mellow-Pinkas scoring system) as the evaluation of patients' symptoms. The antitumor effects of chemotherapy were also investigated. RESULTS: A total of 81 patients were enrolled: 50 were treated with FP, and 31 were treated with DCF. The expansion rate in the length of the narrowest part was significantly increased in the DCF group compared with the FP group. Furthermore, the stenosis index (intraluminal stenotic area/stenotic length) was significantly increased in the DCF group compared with the FP group (112% vs 96%, P = 0.038). Dysphagia score after chemotherapy significantly improved in the DCF group compared to the FP group (P = 0.007). The response rates were 60% in the FP group and 67.7% in the DCF group. Effective histopathological response (improvement to grade 2 or 3) was 24% in the FP group and 38.8% in the DCF group. CONCLUSION: DCF therapy is more effective than FP treatment in the improvement of malignant esophageal stenosis.


Asunto(s)
Trastornos de Deglución , Estenosis Esofágica , Humanos , Estenosis Esofágica/etiología , Cisplatino/uso terapéutico , Docetaxel/uso terapéutico , Constricción Patológica/etiología , Trastornos de Deglución/etiología , Fluorouracilo/uso terapéutico
3.
BMC Surg ; 23(1): 242, 2023 Aug 18.
Artículo en Inglés | MEDLINE | ID: mdl-37596560

RESUMEN

BACKGROUND: The degree of difficulty in the overall procedure and forceps handling encountered by surgeons is greatly influenced by the positional relationship of intrathoracic organs in minimally invasive esophagectomy. This study aimed to identify the anatomical factors associated with the difficulty of minimally invasive esophagectomy assessed by intraoperative injuries and postoperative outcomes. METHODS: Minimally invasive esophagectomy in the left-decubitus position was performed in 258 patients. We defined α (mm) as the anteroposterior distance between the front of the vertebral body and aorta, ß (mm) as the distance between the center of the vertebral body and center of the aorta, and γ (degree) as the angle formed at surgeon's right-hand port site by insertion of lines from the front of aorta and from the front of vertebrae in the computed tomography slice at the operator's right-hand forceps hole level. We retrospectively analyzed the correlations among clinico-anatomical factors, surgeon- or assistant-caused intraoperative organ injuries, and postoperative complications. RESULTS: Intraoperative injuries significantly correlated with shorter α (0.2 vs. 3.9), longer ß (33.0 vs. 30.5), smaller γ (3.0 vs. 4.3), R1 resection (18.5% vs. 8.3%), and the presence of intrathoracic adhesion (46% vs. 26%) compared with the non-injured group. Division of the median values into two groups showed that shorter α and smaller γ were significantly associated with organ injury. Longer ß was significantly associated with postoperative tachycardia onset, respiratory complications, and mediastinal recurrence. Furthermore, the occurrence of intraoperative injuries was significantly associated with the onset of postoperative pulmonary complications. CONCLUSIONS: Intrathoracic anatomical features greatly affected the procedural difficulty of minimally invasive esophagectomy, suggesting that preoperative computed tomography simulation and appropriate port settings may improve surgical outcomes.


Asunto(s)
Neoplasias Esofágicas , Cirujanos , Humanos , Estudios Retrospectivos , Complicaciones Posoperatorias/epidemiología , Aorta , Neoplasias Esofágicas/cirugía
4.
BMC Cancer ; 22(1): 608, 2022 Jun 03.
Artículo en Inglés | MEDLINE | ID: mdl-35658848

RESUMEN

BACKGROUND: The multidisciplinary treatment including induction chemotherapy plus conversion surgery (CS) has attracted attention as a new strategy to improve the outcome of metastatic gastric cancer (MGC). However, it is unclear which patients achieve a good response to chemotherapy and successful CS. Tumor-infiltrating immune cells (TIICs) have been reported to be both prognostic and predictive biomarkers not only in immunotherapy but also in chemotherapy in many cancer types. However, there have been no reports on the usefulness of TIICs as biomarkers in conversion surgery for MGC. The aim of the present study was to evaluate the association between the TIICs and treatment outcome for the multidisciplinary treatment in MGC. METHODS: We retrospectively analyzed 68 MGC patients who received docetaxel plus cisplatin plus S-1 (DCS) therapy between April 2006 and March 2019 in our institute. The number of tumor-infiltrating CD4+, CD8+, Foxp3+lymphocytes, CD68+, CD163+macrophages in pre-treatment endoscopic biopsy samples were evaluated to investigate their predictive value for multidisciplinary treatment. RESULTS: Fifty patients underwent CS following DCS therapy (CS group), whereas 18 patients underwent DCS therapy alone (non-CS group). The median survival time (MST) of CS group was 33.3 months, which was significantly longer than the MST of 9.0 months in non-CS group (p < 0.01). The number of CD163+macrophages was extracted as an independent prognostic factor for overall survival in all patients. There were more cases of high infiltration of CD163+macrophages in non-CS group than in CS group. Furthermore, in CS group, pathological responders to DCS therapy showed low infiltration of CD163+ macrophages, and high infiltration of CD8+lymphocyte. CD163 low group showed a significant prolonged survival compared with CD163 high group in patients who underwent CS (p = 0.02). CONCLUSIONS: The pre-treatment CD163+macrophages infiltration would be a pivotal biomarker for predicting prognosis and pathological response to multidisciplinary treatment among TIICs in MGC. Thus, for patients with low CD163+macrophage infiltration in pre-treatment biopsy sample, diagnostic imaging should be performed frequently during chemotherapy to avoid missing the optimal timing for CS, and CS should be aggressively considered as a treatment option if curative resection is deemed feasible.


Asunto(s)
Neoplasias Gástricas , Antígenos CD , Antígenos de Diferenciación Mielomonocítica , Humanos , Linfocitos Infiltrantes de Tumor , Macrófagos , Pronóstico , Receptores de Superficie Celular , Estudios Retrospectivos , Neoplasias Gástricas/patología
5.
Gastric Cancer ; 25(3): 515-526, 2022 05.
Artículo en Inglés | MEDLINE | ID: mdl-34997450

RESUMEN

BACKGROUND: The role of tumor-stroma interactions in tumor immune microenvironment (TME) is attracting attention. We have previously reported that cancer-associated fibroblasts (CAFs) contribute to the progression of peritoneal metastasis (PM) in gastric cancer (GC), and M2 macrophages and mast cells also contribute to TME of PM. To elucidate the role of CAFs in TME, we established an immunocompetent mouse PM model with fibrosis, which reflects clinical features of TME. However, the involvement of CAFs in the immunosuppressive microenvironment remains unclear. In this study, we investigated the efficacy of Tranilast at modifying this immune tolerance by suppressing CAFs. METHODS: The interaction between mouse myofibroblast cell line LmcMF and mouse GC cell line YTN16 on M2 macrophage migration was investigated, and the inhibitory effect of Tranilast was examined in vitro. Using C57BL/6J mouse PM model established using YTN16 with co-inoculation of LmcMF, TME of resected PM treated with or without Tranilast was analyzed by immunohistochemistry. RESULTS: The addition of YTN16 cell-conditioned medium to LmcMF cells enhanced CXCL12 expression and stimulated M2 macrophage migration, whereas Tranilast inhibited the migration ability of M2 macrophages by suppressing CXCL12 secretion from LmcMF. In PM model, Tranilast inhibited tumor growth and fibrosis, M2 macrophage, and mast cell infiltration and significantly promoted CD8 + lymphocyte infiltration into the tumor, leading to apoptosis of cancer cells by an immune response. CONCLUSION: Tranilast improved the immunosuppressive microenvironment by inhibiting CAF function in a mouse PM model. Tranilast is thus a promising candidate for the treatment of PM.


Asunto(s)
Fibroblastos Asociados al Cáncer , Neoplasias Peritoneales , Neoplasias Gástricas , Animales , Fibroblastos Asociados al Cáncer/patología , Línea Celular Tumoral , Proliferación Celular , Fibroblastos/patología , Fibrosis , Humanos , Macrófagos/patología , Mastocitos , Ratones , Ratones Endogámicos C57BL , Neoplasias Peritoneales/metabolismo , Neoplasias Gástricas/patología , Microambiente Tumoral , ortoaminobenzoatos
6.
Gastric Cancer ; 24(1): 31-44, 2021 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-32488650

RESUMEN

OBJECTIVES: Interleukin-17A (IL-17A) is pro-inflammatory cytokine and acts as profibrotic factor in the fibrosis of various organs. Fibrosis tumor-like peritoneal dissemination of gastric cancer interferes with drug delivery and immune cell infiltration because of its high internal pressure. In this study, we examined the relationship between IL-17A and tissue fibrosis in peritoneal dissemination and elucidated the mechanism of fibrosis induced by IL-17A using human peritoneal mesothelial cells (HPMCs) and a mouse xenograft model. METHODS: Seventy gastric cancer patients with peritoneal dissemination were evaluated. The correlation between IL-17A and fibrosis was examined by immunofluorescence and immunohistochemistry. A fibrosis tumor model was developed based on subcutaneous transplantation of co-cultured cells (HPMCs and human gastric cancer cell line MKN-45) into the dorsal side of nude mice. Mice were subsequently treated with or without IL-17A. We also examined the effect of IL-17A on HPMCs in vitro. RESULTS: There was a significant correlation between IL-17A expression, the number of mast cell tryptase (MCT)-positive cells, and the degree of fibrosis (r = 0.417, P < 0.01). In the mouse model, IL-17A enhanced tumor progression and fibrosis. HPMCs treated with IL-17A revealed changes to a spindle-like morphology, decreased E-cadherin expression, and increased α-SMA expression through STAT3 phosphorylation. Moreover, HPMCs treated with IL-17A showed increased migration. CONCLUSIONS: IL-17A derived from mast cells contributes to tumor fibrosis in peritoneal dissemination of gastric cancer. Inhibiting degranulation of mast cells might be a promising treatment strategy to control organ fibrosis.


Asunto(s)
Interleucina-17/metabolismo , Mastocitos/metabolismo , Neoplasias Peritoneales/metabolismo , Peritoneo/patología , Neoplasias Gástricas/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Animales , Línea Celular Tumoral , Técnicas de Cocultivo , Femenino , Fibrosis , Humanos , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Persona de Mediana Edad , Neoplasias Peritoneales/patología , Neoplasias Gástricas/patología
7.
Gan To Kagaku Ryoho ; 48(4): 581-583, 2021 Apr.
Artículo en Japonés | MEDLINE | ID: mdl-33976055

RESUMEN

The patient was a 61‒year‒old man who had an advanced gastric cancer with peritoneal dissemination. After chemotherapy, intraoperative findings during a total gastrectomy revealed the disappearance of the dissemination nodules. Although adjuvant chemotherapy was performed, the presence of massive ascites led to the recurrence of the peritoneal dissemination 5 months after the surgery. While the chemotherapy regimen was altered, we observed no reduction in malignant ascites. The patient complained of abdominal distention and was admitted to our hospital for symptom management. We performed a cell‒free and concentrated ascites reinfusion therapy(CART)several times. However, symptom management proved difficult; therefore, the patient underwent a peritoneovenous shunt(Denver shunt)placement. After the shunting, we observed no organ injury and improved abdominal distention; however, an asymptomatic coagulopathy was present in the course. Additionally, blood examinations showed increased FDP‒DD and thrombin‒antithrombin complex(TAT). However, 6 months after the shunting, coagulopathy improved and the patient reported the absence of abdominal distention. This report describes a patient with an asymptomatic coagulopathy after Denver shunt placement and evaluated the clinical course by using TAT values.


Asunto(s)
Neoplasias Peritoneales , Derivación Peritoneovenosa , Neoplasias Gástricas , Ascitis/etiología , Ascitis/terapia , Humanos , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Neoplasias Peritoneales/terapia , Neoplasias Gástricas/complicaciones , Neoplasias Gástricas/cirugía
8.
Gan To Kagaku Ryoho ; 48(3): 449-451, 2021 Mar.
Artículo en Japonés | MEDLINE | ID: mdl-33790184

RESUMEN

Although radiation therapy for pelvic cancer leads to improved outcomes, it may cause radiation enteritis. Radiation enteritis is classified as early and late reaction. Late reaction indicate progressive and irreversible changes caused by ischemic changes of the intestinal mucosa. Severe cases require a surgical treatment, which is challenging because of severe adhesions and a high risk of suture failure. In addition, the postoperative course may be unfavorable in some cases. We performed surgery for 4 radiation enteritis cases; however, the postoperative course was unfavorable in 2 cases because of impaired absorption and ileus of the remaining short bowel. These patients could not eat adequately after discharge; therefore, we needed to explain and make them understand the benefits and disadvantages of radiation therapy.


Asunto(s)
Enteritis , Obstrucción Intestinal , Neoplasias Pélvicas , Traumatismos por Radiación , Enteritis/etiología , Humanos , Mucosa Intestinal , Traumatismos por Radiación/etiología
9.
Esophagus ; 18(3): 482-488, 2021 07.
Artículo en Inglés | MEDLINE | ID: mdl-33454818

RESUMEN

BACKGROUND: On the introduction of robot-assisted thoracoscopic esophagectomy (RATE), we refined the robotic system application to enhance our surgical experience obtained through thoracoscopic esophagectomy (TE) in the lateral decubitus position (LDP). Herein, we evaluate our methods introduced to optimize RATE in the LDP. METHODS: We performed RATE in the LDP with camera rotation and manual hand control assignment to reproduce the surgical view and manipulation of open esophagectomy. Forty patients underwent RATE between July 2018 and August 2020. After the initial 30 cases (initial RATE group), we optimized the port arrangement and robot settings in the most recent ten cases (recent RATE group). The surgical results of RATE were compared with those of 30 patients underwent TE between April 2014 and May 2019 selected by propensity score-matched analysis based on cStage (TE group). RESULTS: Operative duration was significantly longer in the initial RATE group than the TE group and the recent RATE group. Thoracic blood loss was significantly less in the initial RATE group than the TE group. Console time was significantly shorter in the recent RATE group than the initial RATE group. There was no surgical mortality in RATE and the surgical morbidity rate was similar in the three groups. CONCLUSIONS: Camera rotation and manual hand control assignment during RATE in the LDP reproduced the surgical view and manipulation of open esophagectomy and TE in the LDP. The robotic platform enabled meticulous dissection and reduced blood loss, but was initially time-consuming. Optimization of the port arrangement minimized operative duration.


Asunto(s)
Neoplasias Esofágicas , Procedimientos Quirúrgicos Robotizados , Robótica , Neoplasias Esofágicas/cirugía , Esofagectomía/efectos adversos , Esofagectomía/métodos , Humanos , Procedimientos Quirúrgicos Robotizados/efectos adversos , Procedimientos Quirúrgicos Robotizados/métodos , Toracoscopía/métodos
10.
BMC Gastroenterol ; 20(1): 325, 2020 Oct 06.
Artículo en Inglés | MEDLINE | ID: mdl-33023478

RESUMEN

BACKGROUND: Postoperative pancreatic fistula (POPF) is a serious complication after gastric cancer surgery. The current study aimed to investigate the significance of the anatomic location of the pancreas as a predictor for POPF in both laparoscopic gastrectomy (LG) and open gastrectomy (OG). METHODS: In total, 233 patients with gastric cancer were assessed retrospectively. We measured the maximum vertical (P-L height; PLH) and horizontal length (P-L depth; PLD) between the upper border of pancreas and the root of left gastric artery on a preoperative CT in the sagittal direction. The maximum length of the vertical line between the surface of the pancreas and the aorta (P-A length), previously reported as prognostic factor of POPF, was also measured. We investigated the correlations between these parameters and the incidence of POPF in LG and OG groups. RESULTS: Among the patients in this study, 118 underwent OG and 115 underwent LG. In LG, the median PLH and P-A length in patients with POPF were significantly longer compared with those without POPF (p = 0.026, 0.034, respectively), but not in OG. There was no significant difference in the median PLD between the patients with or without POPF in both LG and OG. The multivariate analysis demonstrated that PLH (odds ratio [OR] 4.19, 95% confidence interval [CI] 1.57-11.3, P = 0.004) and P-A length (OR 4.06, 95%CI 1.05-15.7, P = 0.042] were independent factors for predicting POPF in LG. However, intraoperative blood loss (OR 2.55, 95%CI 1.05-6.18, P = 0.038) was extracted as an independent factor in OG. The median amylase level in the drained fluid (D-Amy) were significantly higher in patients with high PLH(≥12.4 mm) or high P-A length (≥45 mm) compared with those with low PLH or low P-A length in LG. However, there were no differences in the D-Amy levels by PLH or P-A length in OG patients. CONCLUSIONS: The anatomic location of the pancreas is a specific and independent predictor of POPF in LG but not in OG. PLH is a simple parameter that can evaluate the anatomic position of the pancreas, and it may be useful for preventing POPF after LG.


Asunto(s)
Laparoscopía , Neoplasias Gástricas , Gastrectomía/efectos adversos , Humanos , Páncreas/diagnóstico por imagen , Páncreas/cirugía , Fístula Pancreática/epidemiología , Fístula Pancreática/etiología , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Pronóstico , Estudios Retrospectivos , Neoplasias Gástricas/cirugía
11.
Int J Mol Sci ; 20(24)2019 Dec 17.
Artículo en Inglés | MEDLINE | ID: mdl-31861182

RESUMEN

Insulin-like growth factor-1 (IGF-1) is upregulated in the injured peripheral nerve bundle and controls nociceptive neuronal excitability associated with peripheral nerve injury. Here, we examined the involvement of IGF-1 signaling in orofacial neuropathic pain following infraorbital nerve injury (IONI) in rats. IONI promoted macrophage accumulation in the injured ION, as well as in the ipsilateral trigeminal ganglion (TG), and induced mechanical allodynia of the whisker pad skin together with the enhancement of neuronal activities in the subnucleus caudalis of the spinal trigeminal nucleus and in the upper cervical spinal cord. The levels of IGF-1 released by infiltrating macrophages into the injured ION and the TG were significantly increased. The IONI-induced the number of transient receptor potential vanilloid (TRPV) subfamily type 4 (TRPV4) upregulation in TRPV subfamily type 2 (TRPV2)-positive small-sized, and medium-sized TG neurons were inhibited by peripheral TRPV2 antagonism. Furthermore, the IONI-induced mechanical allodynia was suppressed by TRPV4 antagonism in the whisker pad skin. These results suggest that IGF-1 released by macrophages accumulating in the injured ION binds to TRPV2, which increases TRPV4 expression in TG neurons innervating the whisker pad skin, ultimately resulting in mechanical allodynia of the whisker pad skin.


Asunto(s)
Dolor Facial/metabolismo , Hiperalgesia/metabolismo , Factor I del Crecimiento Similar a la Insulina/metabolismo , Neuralgia/metabolismo , Traumatismos del Nervio Trigémino/metabolismo , Animales , Dolor Facial/fisiopatología , Hiperalgesia/fisiopatología , Macrófagos/metabolismo , Masculino , Neuralgia/fisiopatología , Neuronas/metabolismo , Umbral del Dolor , Ratas Sprague-Dawley , Médula Espinal/metabolismo , Canales Catiónicos TRPV/metabolismo , Ganglio del Trigémino , Traumatismos del Nervio Trigémino/fisiopatología , Vibrisas/inervación , Vibrisas/metabolismo
12.
Gastric Cancer ; 21(1): 55-67, 2018 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-28540637

RESUMEN

BACKGROUND: Scirrhous gastric cancer is an intractable disease with a high incidence of peritoneal dissemination and obstructive symptoms (e.g., ileus, jaundice, and hydronephrosis) arising from accompanying marked fibrosis. Microenvironmental interactions between cancer cells and cancer-associated fibroblasts are the suggested cause of the disease. We elucidated the mechanisms of tumor growth and fibrosis using human peritoneal mesothelial cells (HPMCs) and investigated the effects of tranilast treatment on cells and a xenograft mouse model of fibrosis. METHODS: HPMCs were isolated from surgically excised omentum and their interaction with MKN-45 gastric cancer cells was investigated using co-culture. Furthermore, a fibrosis tumor model was developed based on subcutaneous transplantation of co-cultured cells into the dorsal side of nude mice to form large fibrotic tumors. Mice were subsequently treated with or without tranilast. RESULTS: The morphology of HPMCs treated with transforming growth factor (TGF)-ß1 changed from cobblestone to spindle-type. Moreover, E-cadherin was weakly expressed whereas high levels of α-smooth muscle actin expression were observed. TGF-ß-mediated epithelial-mesenchymal transition-like changes in HPMCs were inhibited in a dose-dependent manner following tranilast treatment through inhibition of Smad2 phosphorylation. In the mouse model, tumor size decreased significantly and fibrosis was inhibited in the tranilast treatment group compared with that in the control group. CONCLUSIONS: Tranilast acts on the TGF-ß/Smad pathway to inhibit interactions between cancer cells and cancer-associated fibroblasts, thereby inhibiting tumor growth and fibrosis. This study supports the hypothesis that tranilast represents a novel strategy to prevent fibrous tumor establishment represented by peritoneal dissemination.


Asunto(s)
Adenocarcinoma/patología , Fibroblastos/efectos de los fármacos , Neoplasias Gástricas/patología , ortoaminobenzoatos/farmacología , Animales , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Técnicas de Cocultivo , Progresión de la Enfermedad , Transición Epitelial-Mesenquimal/efectos de los fármacos , Fibroblastos/patología , Fibrosis , Humanos , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Epiplón/citología , Ensayos Antitumor por Modelo de Xenoinjerto
13.
Eur J Neurosci ; 46(6): 2190-2202, 2017 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-28834578

RESUMEN

Iatrogenic trigeminal nerve injuries remain a common and complex clinical problem. Satellite glial cell (SGC) activation, associated phosphorylation of extracellular signal-regulated kinase (ERK), and neuropeptide expression in the trigeminal ganglion (TG) are known to be involved in trigeminal neuropathic pain related to trigeminal nerve injury. However, the involvement of these molecules in orofacial neuropathic pain mechanisms is still unknown. Phosphorylation of ERK1/2 in lingual nerve crush (LNC) rats was observed in SGCs. To evaluate the role of neuron-SGC interactions under neuropathic pain, calcitonin gene-related peptide (CGRP)-immunoreactive (IR), phosphorylated ERK1/2 (pERK1/2)-IR and glial fibrillary acidic protein (GFAP)-IR cells in the TG were studied in LNC rats. The number of CGRP-IR neurons and neurons encircled with pERK1/2-IR SGCs was significantly larger in LNC rats compared with sham rats. The percentage of large-sized CGRP-IR neurons was significantly higher in LNC rats. The number of CGRP-IR neurons, neurons encircled with pERK1/2-IR SGCs, and neurons encircled with GFAP-IR SGCs was decreased following CGRP receptor blocker CGRP8-37 or mitogen-activated protein kinase/ERK kinase 1 inhibitor PD98059 administration into the TG after LNC. Reduced thresholds to mechanical and heat stimulation to the tongue in LNC rats were also significantly recovered following CGRP8-37 or PD98059 administration. The present findings suggest that CGRP released from TG neurons activates SGCs through ERK1/2 phosphorylation and TG neuronal activity is enhanced, resulting in the tongue hypersensitivity associated with lingual nerve injury. The phenotypic switching of large myelinated TG neurons expressing CGRP may account for the pathogenesis of tongue neuropathic pain.


Asunto(s)
Sistema de Señalización de MAP Quinasas , Neuralgia/metabolismo , Neuronas/metabolismo , Células Satélites Perineuronales/metabolismo , Ganglio del Trigémino/metabolismo , Animales , Proteína Ácida Fibrilar de la Glía/metabolismo , Nervio Lingual/metabolismo , Nervio Lingual/fisiología , Masculino , Proteína Quinasa 1 Activada por Mitógenos/metabolismo , Proteína Quinasa 3 Activada por Mitógenos/metabolismo , Neuralgia/fisiopatología , Neuronas/fisiología , Fenotipo , Ratas , Ratas Sprague-Dawley , Receptores de Péptido Relacionado con el Gen de Calcitonina/metabolismo , Células Satélites Perineuronales/fisiología , Ganglio del Trigémino/citología , Ganglio del Trigémino/fisiología
14.
BMC Cancer ; 17(1): 294, 2017 04 27.
Artículo en Inglés | MEDLINE | ID: mdl-28449652

RESUMEN

BACKGROUND: The theory of extravasated platelet aggregation in cancer lesions was recently introduced. We investigated the association of platelet aggregation in gastric cancer stroma with clinicopathological features, chemotherapeutic response, pathological response, and survival. METHODS: The study comprised 78 patients with advanced gastric cancer who had undergone gastrectomy with or without combination of docetaxel, cisplatin and S-1 (DCS) as preoperative chemotherapy between 2005 and 2014. The patients were divided into two groups: patients who had received preoperative DCS therapy forming the p-DCS group and patients who had not received preoperative DCS therapy forming the control group. The 39 patients in the control group had received gastrectomy and postoperative chemotherapy of S-1 alone. Platelet aggregation in biopsy specimens before preoperative DCS therapy in the p-DCS group and at the time of diagnosis in the control group were evaluated using CD42b immunohistochemical staining. RESULTS: Twenty-four patients in the p-DCS group and 19 in the control group were found to have platelet aggregation in their cancer stroma. Patients with histologically confirmed platelet aggregation had significantly higher rates of chemoresistance (58.3%) than those without platelet aggregation (20.0%) (P = 0.019). According to multivariate analysis, CD42b expression (odds ratio: 5.102, 95% confidence interval: 1.039-25.00, P = 0.045) was correlated with chemoresistance. CD42b expression and histological non-responder status were both significantly correlated with poor overall survival (OS) (P = 0.012, P = 0.016); however, RECIST was not correlated with OS. In the control group, CD42b expression was also significantly correlated with poor overall survival (OS) (P = 0.033). In the p-DCS group, according to multivariate analysis, male sex (hazard ratio: 0.281, 95% confidence interval: 0.093-0.846, P = 0.024) was correlated with good prognosis and CD42b expression (hazard ratio: 4.406, 95% confidence interval: 1.325-14.65, P = 0.016) with poor prognosis. CONCLUSIONS: This study suggests that platelets in gastric cancer stroma may create a favorable microenvironment for chemoresistance. CD42b immunohistochemical staining of biopsy specimens is a promising candidate for being a prognostic marker in patients with gastric cancer.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Biomarcadores/sangre , Neoplasias Hepáticas/mortalidad , Agregación Plaquetaria , Neoplasias Gástricas/mortalidad , Adulto , Anciano , Anciano de 80 o más Años , Cisplatino/administración & dosificación , Docetaxel , Combinación de Medicamentos , Femenino , Estudios de Seguimiento , Humanos , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/secundario , Metástasis Linfática , Masculino , Persona de Mediana Edad , Clasificación del Tumor , Ácido Oxónico/administración & dosificación , Cuidados Preoperatorios , Pronóstico , Estudios Retrospectivos , Neoplasias Gástricas/tratamiento farmacológico , Neoplasias Gástricas/patología , Tasa de Supervivencia , Taxoides/administración & dosificación , Tegafur/administración & dosificación
15.
Eur J Oral Sci ; 125(6): 444-452, 2017 12.
Artículo en Inglés | MEDLINE | ID: mdl-29023985

RESUMEN

The P2Y12 receptor expressed in satellite cells of the trigeminal ganglion is thought to contribute to neuropathic pain. The functional interaction between neurons and satellite cells via P2Y12 receptors and phosphorylated extracellular signal-regulated kinase 1/2 (pERK1/2) underlying neuropathic pain in the tongue was evaluated in this study. Expression of P2Y12 receptor was enhanced in pERK1/2-immunoreactive cells encircling trigeminal ganglion neurons after lingual nerve crush. The administration to lingual nerve crush rats of a selective P2Y12 receptor antagonist, MRS2395, attenuated tongue hypersensitivity to mechanical and heat stimulation and suppressed the increase in the relative numbers of calcitonin gene-related peptide (CGRP)-immunoreactive neurons and neurons encircled by pERK1/2-immunoreactive cells. Administration of the P2Y1,12,13 receptor agonist, 2-(methylthio)adenosine 5'-diphosphate trisodium salt hydrate (2-MeSADP), to naïve rats induced neuropathic pain in the tongue, as in lingual nerve crush rats. Co-administration of 2-MeSADP + MRS2395 to naïve rats did not result in hypersensitivity of the tongue. The relative number of CGRP-immunoreactive neurons increased following this co-administration, but to a lesser degree than observed in 2-MeSADP-administrated naïve rats, and the relative number of neurons encircled by pERK1/2-immunoreactive cells did not change. These results suggest that the interaction between activated satellite cells and CGRP-immunoreactive neurons via P2Y12 receptors contributes to neuropathic pain in the tongue associated with lingual nerve injury.


Asunto(s)
Péptido Relacionado con Gen de Calcitonina/metabolismo , Traumatismos del Nervio Lingual/metabolismo , Neuralgia/metabolismo , Células Satélites Perineuronales/metabolismo , Lengua/inervación , Ganglio del Trigémino/metabolismo , Adenina/análogos & derivados , Adenina/farmacología , Adenosina Difosfato/análogos & derivados , Adenosina Difosfato/farmacología , Animales , Proteína Ácida Fibrilar de la Glía/metabolismo , Inmunohistoquímica , Masculino , Microscopía Fluorescente , Neuronas/metabolismo , Ratas , Ratas Sprague-Dawley , Receptores Purinérgicos P2/metabolismo , Receptores Purinérgicos P2Y12 , Tionucleótidos/farmacología , Valeratos/farmacología , eIF-2 Quinasa/metabolismo
17.
Palliat Support Care ; 14(3): 269-77, 2016 06.
Artículo en Inglés | MEDLINE | ID: mdl-27210590

RESUMEN

OBJECTIVE: The present study sought to examine the impact of physical symptoms, facial disfigurement, adequacy of preoperative information, and social support on anxiety and depression in Japanese patients with head and neck cancer (HNC) who had undergone surgery. METHOD: A cross-sectional study with 194 patients was conducted using a self-administered questionnaire. This instruments included the Hospital Anxiety and Depression Scale (HADS), the European Organization for Research and Treatment of Cancer (EORTC) Head and Neck cancer module (QLQ-H&N35), and a Social Support Scale developed by Okabayashi et al. (1997). RESULTS: The majority (56.7%) had surgery two or more years before completing the questionnaire. More than 25% of respondents showed anxiety or depression. Higher levels of perceived social support were associated with lower rates of anxiety and depression (p < 0.01). Sensory problems were associated with anxiety, and reduced sexuality was associated with depression (p < 0.01). Perceived disfigurement and adequacy of preoperative information were not associated with anxiety or depression. SIGNIFICANCE OF RESULTS: Survivors of HNC experience anxiety and depression for an extended period of time. Social support may alleviate the severity of these disorders. More research is needed to confirm the impact of facial disfigurement and that of the preoperative information provided by surgeons on psychological distress in HNC patients.


Asunto(s)
Anomalías Congénitas/psicología , Neoplasias de Cabeza y Cuello/cirugía , Calidad de Vida/psicología , Procedimientos Quirúrgicos Operativos/efectos adversos , Sobrevivientes/psicología , Anciano , Ansiedad/etiología , Ansiedad/psicología , Anomalías Congénitas/etiología , Estudios Transversales , Depresión/etiología , Depresión/psicología , Femenino , Neoplasias de Cabeza y Cuello/complicaciones , Neoplasias de Cabeza y Cuello/psicología , Humanos , Japón , Masculino , Persona de Mediana Edad , Psicometría/instrumentación , Psicometría/métodos , Apoyo Social , Procedimientos Quirúrgicos Operativos/psicología , Encuestas y Cuestionarios
18.
J Surg Case Rep ; 2024(2): rjae034, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38322358

RESUMEN

The incidence of gastric tube cancer (GTC) is increasing due to the improved prognosis of patients after esophagectomy for esophageal cancer. Total resection of the gastric tube is expected to be curative for patients with GTC. However, several studies have reported that this procedure is associated with high mortality and morbidity rates. We here present a case of GTC without lymph node metastasis in a patient who underwent partial resection of a gastric tube via thoracoscopic-endoscopic cooperative surgery. No postoperative complications or recurrence was observed. This procedure is a favorable and minimally invasive procedure for GTC without lymph node metastasis.

19.
J Laparoendosc Adv Surg Tech A ; 34(5): 393-400, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38593412

RESUMEN

Introduction: The use of robotic platform for gastrectomy for gastric cancer is rapidly increasing. This study aimed to describe the perioperative outcomes of 12 patients who underwent robotic gastrectomy for gastric cancer using the hinotori™ surgical robot system (hinotori), a novel robot-assisted surgical platform, and compare the outcomes with the existing system, the da Vinci® Surgical System (DVSS). Methods: This study included 12 consecutive patients with gastric cancer who underwent robotic gastrectomy for gastric cancer using the hinotori between March 2023 and September 2023 at our institution. The comprehensive perioperative outcomes of these patients were retrospectively analyzed and compared to 11 patients who underwent robotic gastrectomy using the DVSS during the same period. Results: The median age and body mass index were 71 years (range: 56-86) and 22.7 kg/m2 (range: 16.1-26.7). Distal and total gastrectomy were performed in 8 and 4 patients, respectively. The median console time and operation times were 187 (range: 112-270) and 252 minutes (range: 173-339), respectively. The median blood loss was 3 mL (range: 2-5). No intra- or postoperative complications were observed. There were no significant differences in perioperative outcomes between the hinotori and the DVSS. Conclusions: Robotic gastrectomy for gastric cancer using the hinotori is a feasible procedure and achieved perioperative outcomes similar to that using the DVSS. Clinical Trial Registration number: 114167-1.


Asunto(s)
Gastrectomía , Procedimientos Quirúrgicos Robotizados , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/cirugía , Gastrectomía/métodos , Gastrectomía/instrumentación , Procedimientos Quirúrgicos Robotizados/métodos , Procedimientos Quirúrgicos Robotizados/instrumentación , Persona de Mediana Edad , Femenino , Masculino , Anciano , Estudios Retrospectivos , Anciano de 80 o más Años , Tempo Operativo , Resultado del Tratamiento
20.
Oncol Lett ; 27(4): 147, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38385106

RESUMEN

Reflux of gastroduodenal contents into the esophagus leads to the development of esophagitis and inflammation-associated pathologies, such as Barrett's esophagus (BE) and esophageal adenocarcinoma (EAC). The role of the lipoxygenase (LOX) pathway in carcinogenesis has been recently reported; however, its involvement in esophageal carcinogenesis remains unclear. To address this, the present study investigated the potential of pranlukast, a cysteinyl leukotriene receptor-1 antagonist, to suppress the progression of BE and EAC in a rat duodenogastroesophageal reflux (DGER) model. Male Wistar rats that underwent DGER were divided into two groups. One group was fed commercial chow (control group), and the other was fed experimental chow containing pranlukast (pranlukast group). The rats were sacrificed at 10, 20, 30 and 40 weeks after surgery, and their esophagi were examined. Expression levels of 5-LOX, CD68, IL-8, VEGF and Ki-67 were investigated using immunohistochemistry, and apoptosis was analyzed using the TUNEL method. In the pranlukast group, esophagitis was milder, and the incidence of BE and EAC was significantly lower (P<0.05) compared with that in the control group at 40 weeks after surgery. The number of cells positive for IL-8 and VEGF were significantly lower in the pranlukast group compared with the control group. Proliferative activity was also lower in the pranlukast group compared with the control group (P<0.05). Pranlukast treatment increased apoptosis (P<0.05). Overall, Pranlukast suppressed esophageal carcinogenesis in a rat DGER model, decreasing inflammatory cytokines such as IL-8 and VEGF.

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