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1.
Sci Rep ; 11(1): 17946, 2021 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-34504174

RESUMO

Fluorescence imaging of tumours facilitates rapid intraoperative diagnosis. Thus far, a promising activatable fluorescence probe for hepatocellular carcinoma (HCC) has not been developed. Herein, the utility of the fluorescence imaging of HCC using a ß-galactosidase (ß-Gal)-activatable fluorescence probe SPiDER-ßGal was examined. ß-Gal activity was measured in cryopreserved tissues from 68 patients. Live cell imaging of HCC cell lines and imaging of tumour-bearing model mice were performed using SPiDER-ßGal. Furthermore, fluorescence imaging was performed in 27 freshly resected human HCC specimens. In cryopreserved samples, ß-Gal activity was significantly higher in tumour tissues than in non-tumour tissues. Fluorescence was observed in HCC cell lines. In mouse models, tumours displayed stronger fluorescence than normal liver tissue. In freshly resected specimens, fluorescence intensity in the tumour was significantly higher than that in non-tumour liver specimens as early as 2 min after spraying. Receiver operating characteristic curves were generated to determine the diagnostic value of SPiDER-ßGal 10 min after its spraying; an area under the curve of 0.864, sensitivity of 85.2%, and specificity of 74.1% were observed for SPiDER-ßGal. SPiDER-ßGal is useful for the rapid fluorescence imaging of HCC. Fluorescence imaging guided by SPiDER-ßGal would help surgeons detect tumours rapidly and achieve complete liver resection.

2.
Photodiagnosis Photodyn Ther ; 35: 102420, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34242818

RESUMO

BACKGROUND: Accurate diagnosis of peritoneal metastasis in gastric cancer (GC) is important to determine the appropriate treatment. This study aimed to examine whether matrix metalloprotease-14 (MMP-14) was a candidate enzyme in fluorescence imaging for the diagnosis of peritoneal metastasis in GC. METHODS: GC and normal peritoneal (NP) tissues from 96 and 20 patients, respectively were evaluated for MMP-14 expression. Live cell imaging of GC cell lines (NUGC4, MKN45, MKN74, HGC-27, and Kato-III) was performed using the MMP-14-activatable fluorescence probe; BODIPY-MMP. Furthermore, the overall survival (OS) was calculated in all patients (n = 96). RESULTS: MMP-14 expression was significantly higher in GC tissues (median: 3.57 ng/mg protein; range:0.64-24.4 ng/mg protein) than in NP tissues (median: 1.34 ng/mg protein; median: 0.53-3.09 ng/mg protein) (P < 0.01). Receiver operating characteristic curves showed that the area under the curve, sensitivity, and specificity were 0.907, 84.4%, and 90.0%, respectively. In live cell imaging using the BODIPY-MMP, fluorescence was observed in five GC cell lines. In the analysis of OS, the high expression of the MMP-14 group had a significantly poorer OS rate than the low expression of the MMP-14 group (P = 0.02). In the multivariate analyses, MMP-14 expression was an independent risk factor for OS (hazard ratio: 2.33; 95 % confidence interval: 1.05-5.45; P = 0.04). CONCLUSION: MMP-14 is a promising enzyme in intraoperative fluorescence imaging for peritoneal metastasis in GC, especially in patients with poor prognosis.


Assuntos
Neoplasias Peritoneais , Fotoquimioterapia , Neoplasias Gástricas , Biomarcadores Tumorais , Humanos , Metaloproteinase 14 da Matriz , Neoplasias Peritoneais/diagnóstico por imagem , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes , Prognóstico , Neoplasias Gástricas/diagnóstico por imagem
3.
Anticancer Res ; 41(7): 3657-3665, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34230164

RESUMO

BACKGROUND/AIM: We attempted to stratify prognosis using the modified Journal of Hepato-Biliary-Pancreatic Sciences (mJHBPS) nomogram upon identification of colorectal liver metastasis (CRLM) and to investigate which strategy is better, surgery first (SF) or chemotherapy first (CF), in each risk group. PATIENTS AND METHODS: A total of 137 patients with CRLM who underwent resection of the primary tumor were included. Patients with brain, bone, or perihilar lymph node metastases were excluded. Patients were scored using the mJHBPS nomogram upon identification of CRLM. Prognosis was investigated using event-free survival (EFS) and overall survival (OS). RESULTS: The nomogram allowed stratification of patients using EFS and OS: low-risk (0-6 score, n=38), medium-risk (7-11 score, n=42), and high-risk (12≥ score, n=57). In the low-risk group, the EFS and OS of the CF group were significantly poorer than those of the SF group (p=0.019 and p=0.014, respectively). CF was an independent prognostic factor for both EFS and OS. CONCLUSION: The mJHBPS nomogram can stratify CRLM patients with sufficient differences in EFS and OS. SF was recommended for patients in the low-risk group.


Assuntos
Neoplasias Colorretais/patologia , Neoplasias Colorretais/terapia , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/terapia , Fígado/patologia , Idoso , Feminino , Humanos , Metástase Linfática/patologia , Masculino , Nomogramas , Pâncreas/patologia , Prognóstico , Intervalo Livre de Progressão , Estudos Retrospectivos
4.
Sci Rep ; 11(1): 10664, 2021 05 21.
Artigo em Inglês | MEDLINE | ID: mdl-34021168

RESUMO

Diagnosis of peritoneal metastasis in gastric cancer (GC) is essential for determining appropriate therapeutic strategies and avoiding non-essential laparotomy or gastrectomy. Recently, a variety of activatable fluorescence probes that can detect enzyme activities have been developed for cancer imaging. The aim of this study was to identify the key enzyme involved in peritoneal metastasis in GC. The enzymatic activity of gamma-glutamyl transpeptidase, dipeptidyl peptidase IV, and ß-galactosidase (ß-Gal) was assessed in lysates prepared from preserved human GC (n = 89) and normal peritoneal (NP; n = 20) samples. ß-Gal activity was significantly higher in the human GC samples than in NP samples, whereas no differences were observed in the activities of the other enzymes. Therefore, we used SPiDER-ßGal, a fluorescent probe that can be activated by ß-Gal, for imaging GC cell lines, peritoneal metastasis in a mouse model, and fresh human resected GC samples (n = 13). All cell lines showed fluorescence after applying SPiDER-ßGal, and metastatic nodules in the mice gradually developed high fluorescence that could be visualized with SPiDER-ßGal. The human GC samples showed significantly higher fluorescence than NP samples. ß-Gal is a useful target enzyme for fluorescence imaging of peritoneal metastasis in GC.

5.
World J Clin Cases ; 9(14): 3424-3431, 2021 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-34002154

RESUMO

BACKGROUND: Gangrenous cholecystitis is a form of acute cholecystitis which involves gangrenous alterations in the gallbladder wall and it often follows an acute and serious course. We herein report on two cases of very elderly people diagnosed early with gangrenous cholecystitis, who safely underwent laparoscopic cholecystectomy (LC) and both demonstrated a good outcome. CASE SUMMARY: Case 1: An 89-year-old female. She underwent abdominal contrast-enhanced computed tomography (CECT) due to abdominal pain and diarrhea. Her gallbladder wall indicated the absence of contrast enhancement, thus leading to diagnosis of gangrenous cholecystitis and she therefore underwent LC. Although her gallbladder demonstrated diffuse necrosis and it was also partly perforated, she was able to be discharged without any serious complications. Case 2: A 91-year-old female. She made an emergency visit with a chief complaint of abdominal pain. Abdominal CECT revealed swelling of the gallbladder and an ambiguous continuity of the gallbladder wall. She was diagnosed with gangrenous cholecystitis and underwent LC. Her gallbladder had swelling and diffuse necrosis. Although her preoperative blood culture was positive, she showed a good outcome following surgery. CONCLUSION: Although a definite diagnosis of gangrenous cholecystitis is difficult to make prior to surgery, if an early diagnosis can be made and appropriate treatment can be carried out, then even very elderly individuals may be discharged without major complications.

6.
Surg Today ; 51(3): 422-431, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32772168

RESUMO

PURPOSE: The long-term prognostic impact of the hemoglobin A1c levels has not yet been evaluated in patients with gastric cancer. The present study investigated the clinical significance of the hemoglobin A1c levels in patients with gastric cancer. METHODS: We enrolled 294 patients with stage II, III, or IV gastric cancer who underwent gastrectomy. The patients were divided into high preoperative hemoglobin A1c (> 6.0%) and low preoperative hemoglobin A1c (≤ 6.0%) groups. RESULTS: In patients with stage III gastric cancer with severe postoperative complications, the high preoperative hemoglobin A1c group had a significantly worse prognosis than the low preoperative hemoglobin A1c group (p = 0.0409). In patients without severe postoperative complications, the high preoperative hemoglobin A1c group had a significantly favorable prognosis compared with the low preoperative hemoglobin A1c group (p = 0.0348). CONCLUSION: The prognosis of patients with stage III gastric cancer having high preoperative hemoglobin A1c levels greatly depended on the presence or absence of postoperative complications. To avoid postoperative complications, optimal perioperative management and personalized treatments are critical, particularly for these patients.


Assuntos
Gastrectomia/efeitos adversos , Hemoglobina A Glicada/metabolismo , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/cirurgia , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Assistência Perioperatória , Complicações Pós-Operatórias/prevenção & controle , Período Pré-Operatório , Prognóstico , Neoplasias Gástricas/patologia
7.
Oncol Lett ; 20(4): 82, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32863915

RESUMO

5-Aminolevulinic acid-mediated photodynamic therapy (ALA-PDT) is a minimally invasive therapeutic modality used in the management of various cancers, but to a lesser extent for esophageal cancer (EC). The current study investigated the antitumor effects of ALA-PDT. Human EC cells were treated with ALA, after which ALA-induced fluorescence was examined under a fluorescence microscope. The cytotoxic effects of ALA-PDT were assessed using three types of LEDs (blue, green and red) in vitro and in vivo. Subcutaneous tumor model mice was constructed with KYSE150 cells. ALA-PDT was performed once a week for 4 weeks and tumor weights were measured. A popliteal lymph node (PLN) metastasis murine model was generated using KYSE150 cells. KYSE150 cells were inoculated into the left footpad of nude mice. ALA-PDT was performed on the footpad once a week for 4 weeks. PLNs were then removed 3 weeks after the last treatment. The lymph nodes were evaluated by hematoxylin and eosin staining. Red fluorescence of protoporphyrin IX (PpIX) was observed in all EC cell lines. ALA-PDT using LEDs exerted significant antitumor effects in vitro and in vivo. The antitumor effects of ALA-PDT with blue LED were the strongest, followed by green and red LEDs. The number of metastasized PLNs was significantly smaller in the ALA-PDT group (0%) than in the control group (37.5%). The present results indicated that ALA-PDT is effective for EC.

8.
Anticancer Res ; 40(6): 3163-3167, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32487611

RESUMO

BACKGROUND/AIM: Ultrasonically activated surgical devices (USADs) have become indispensable instruments for gastrointestinal surgery. In this study, we investigated the oncological safety of the use of USADs. MATERIALS AND METHODS: We harvested and cultivated the splashes and mist scattered from an USAD when cutting MKN45-derived cancer nodules. Seven days later, we observed viable cancer cells and the total number of cells was counted. The histopathology of the nodules cut by the USAD was also examined. RESULTS: The existence of viable cancer cells was confirmed by ex vivo cell culture. The number of viable cancer cells was reduced by slow grasping of the USAD. The surface of cancerous tissue cut by the USAD was partially heat-denatured, however, there were some parts in which cancerous tissue was exposed on the surface. CONCLUSION: Surgeons should recognize the possibility that cancer cells may be scattered by USAD use.


Assuntos
Procedimentos Cirúrgicos do Sistema Digestório/métodos , Neoplasias Gástricas/diagnóstico por imagem , Neoplasias Gástricas/cirurgia , Terapia por Ultrassom/métodos , Animais , Linhagem Celular Tumoral , Feminino , Humanos , Camundongos , Camundongos Nus , Neoplasias Gástricas/patologia
9.
Surg Case Rep ; 5(1): 28, 2019 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-30778694

RESUMO

BACKGROUND: Polysplenia refers to the presence of two or more equal-sized spleens. Very rarely, one of the multiple spleens may develop torsion and infarction. CASE PRESENTATION: A 21-year-old woman presented with left upper quadrant pain, the cause of which could not be diagnosed. She returned to our hospital, 2 days later, without any pain improvement. Enhanced computed tomography showed splenic infarction and polysplenia. Initially, we could not identify the cause of the infarction and started conservative therapy, which did not result in any improvement. Hence, we performed a splenectomy, after securing informed consent. Because the patient was a young woman, we opted for a laparoscopic approach. During surgery, we identified the cause of the infarction as spleen pedicle torsion; the infarcted spleen was excised using an automated suturing device. We completed the laparoscopic surgery without converting it to an open laparotomy, and the patient was discharged 4 days later. This was a rare case of polysplenia with splenic torsion. CONCLUSION: Laparoscopic splenectomy is minimally invasive and has cosmetic advantages. Thus, this approach may be considered as a treatment option for this condition.

10.
Sci Rep ; 8(1): 17781, 2018 12 12.
Artigo em Inglês | MEDLINE | ID: mdl-30542087

RESUMO

Rapid diagnosis of metastatic lymph nodes (mLNs) of colorectal cancer (CRC) is desirable either intraoperatively or in resected fresh specimens. We have developed a series of activatable fluorescence probes for peptidase activities that are specifically upregulated in various tumors. We aimed to discover a target enzyme for detecting mLNs of CRC. Among our probes, we found that gGlu-HMRG, a gamma-glutamyl transpeptidase (GGT)-activatable fluorescence probe, could detect mLNs. This was unexpected, because we have previously reported that gGlu-HMRG could not detect primary CRC. We confirmed that the GGT activity of mLNs was high, whereas that of non-metastatic lymph nodes and CRC cell lines was low. We investigated the reason why GGT activity was upregulated in mLNs, and found that GGT was induced under conditions of hypoxia or low nutritional status. We utilized this feature to achieve rapid detection of mLNs with gGlu-HMRG. GGT appears to be a promising candidate enzyme for fluorescence imaging of mLNs.


Assuntos
Neoplasias Colorretais/metabolismo , Corantes Fluorescentes/metabolismo , Linfonodos/metabolismo , Metástase Linfática/patologia , gama-Glutamiltransferase/metabolismo , Animais , Linhagem Celular Tumoral , Neoplasias Colorretais/patologia , Feminino , Fluorescência , Células HCT116 , Células HT29 , Humanos , Linfonodos/patologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Regulação para Cima/fisiologia
11.
Oncol Lett ; 16(1): 821-828, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29963150

RESUMO

Peritoneal metastasis is an important prognostic factor for pancreatic cancer. The present study evaluated the possibility of diagnosing peritoneal metastasis by a photodynamic diagnosis using 5-aminolevulinic acid (5-ALA-PDD). In vitro, protoporphyrin IX (PpIX) accumulation was examined in the AsPC-1-GFP cell line following 5-ALA hydrochloride administration. In vivo, AsPC-1-GFP cells were injected into the peritoneal cavities of mice. Three weeks later 5-ALA hydrochloride was intraperitoneally administered to the mice. The peritoneal nodules were observed under fluorescence excitation. A total of 34 patients were enrolled in the present study who were clinically diagnosed with pancreatic malignancy. 5-ALA hydrochloride was orally administered to the patients prior to surgery. During the operation the abdominal cavity was observed under white light and fluorescence. In vitro and in vivo, it was confirmed that PpIX-induced red fluorescence. In 9 patients peritoneal nodules suspected to be peritoneal metastasis were observed under white light. In 4 of the 9 patients nodules were detected on the basis of the fluorescence images. Fluorescent nodules were histopathologically diagnosed as metastatic. In the present study it was confirmed that 5-ALA-PDD holds promise for the rapid diagnosis of peritoneal metastasis in patients with pancreatic cancer.

12.
J Am Chem Soc ; 140(5): 1767-1773, 2018 02 07.
Artigo em Inglês | MEDLINE | ID: mdl-29368925

RESUMO

Carboxypeptidases (CPs) are a family of hydrolases that cleave one or more amino acids from the C-terminal of peptides or proteins. However, methodology to monitor the activities of CPs is poorly developed. Here, we present the first versatile design strategy to obtain activatable fluorescent probes for CPs by utilizing intramolecular spirocyclization of rhodamine to translate the "aliphatic carboxamide to aliphatic carboxylate" structural conversion catalyzed by CPs into dynamic fluorescence activation. Based on this novel strategy, we developed probes for carboxypeptidases A and B. One of these probes was able to detect pancreatic juice leakage in mice ex vivo, suggesting that its suitability for intraoperative diagnosis of pancreatic fistula. This design strategy should be broadly applicable to CPs, as well as other previously untargetable enzymes, enabling development of fluorescent probes to study various pathological and biological processes.

13.
World J Surg ; 40(11): 2796-2802, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27307087

RESUMO

BACKGROUND: The prognostic value of the neutrophil-to-lymphocyte ratio (NLR) has been reported in several cancers included colorectal cancer; however, it is not clear if there is an association between NLR and cancer-specific survival in colorectal cancer. And the optimal cut-off value is controversial. This study was designed to assess the prognostic value of preoperative NLR in colorectal cancer patients. METHODS: Total 823 consecutive patients who underwent surgery for all stages of colorectal cancer in our hospital between January 2006 and December 2011 were included in the study. Preoperative NLR was calculated from their hospital records. RESULTS: Using the receiver-operating characteristic curve, we found that the optimal preoperative NLR cut-off value that was strongly associated with cancer-specific survival was 2.1. Using this value, 505 patients were identified as having high NLR (≥2.1) and 397 patients were identified as having low NLR (<2.1). High NLR was associated with preoperative serum albumin values <4.0 g/dl (p < 0.001), positive preoperative serum C-reactive protein (CRP; p < 0.001), preoperative carcinoembryonic antigen (CEA) values ≥5.0 ng/dl (p = 0.003), and stage progression (p = 0.002). Cox proportional hazard analyses identified preoperative high NLR as an independent poor prognostic factor (p = 0.020, HR 1.66 (95 % CI: 1.08-2.63)). When comparing stage of disease, preoperative high-NLR patients with Stage III disease (p = 0.024) and Stage IV disease (p = 0.036) had significantly poorer prognoses. CONCLUSIONS: In this study, we have demonstrated that preoperative NLR ≥2.1 was a prognostic indicator for cancer-specific survival of colorectal cancer patients.


Assuntos
Neoplasias Colorretais/sangue , Neoplasias Colorretais/mortalidade , Linfócitos/metabolismo , Neutrófilos/metabolismo , Idoso , Proteína C-Reativa/análise , Antígeno Carcinoembrionário/sangue , Neoplasias Colorretais/cirurgia , Feminino , Humanos , Masculino , Período Pré-Operatório , Prognóstico , Estudos Retrospectivos , Albumina Sérica
14.
Anticancer Res ; 36(2): 807-13, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26851044

RESUMO

BACKGROUND: This study was designed to assess the prognostic role of body weight loss (BWL) after curative gastrectomy for gastric cancer patients. PATIENTS AND METHODS: We analyzed a total of 102 consecutive patients who underwent curative gastrectomy for stage II or III gastric cancer between 2005 and 2011. Postoperative BWL during the first 6 months in patients was calculated from their hospital records. RESULTS: Postoperative BWL was significantly higher in patients with tumours in the upper stomach, total gastrectomy, or subsequent recurrence. A postoperative BWL of 12% was the optimal cut-off value, which was strongly associated with subsequent recurrence. Patients with a postoperative BWL of 12% or higher did not have poorer overall survival but did have significantly poorer disease-free survival than patients with BWL of less than 12%. Cox proportional hazard analyses revealed that a postoperative BWL of 12% or higher was an independent prognostic factor of poor disease-free survival. CONCLUSION: High BWL after curative gastrectomy is related to recurrence in patients with gastric cancer.


Assuntos
Gastrectomia/efeitos adversos , Recidiva Local de Neoplasia , Neoplasias Gástricas/cirurgia , Perda de Peso , Progressão da Doença , Intervalo Livre de Doença , Gastrectomia/mortalidade , Humanos , Japão , Estimativa de Kaplan-Meier , Análise Multivariada , Estadiamento de Neoplasias , Modelos de Riscos Proporcionais , Medição de Risco , Fatores de Risco , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/patologia , Fatores de Tempo , Resultado do Tratamento
15.
Surg Case Rep ; 1(1): 77, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26380170

RESUMO

Pyogenic liver abscess (PLA) complicated by inferior vena caval (IVC) thrombosis is rare but life-threatening. We experienced a case of PLA complicated by an IVC thrombus close to the right atrium after pancreatoduodenectomy. A 75-year-old man had undergone pancreatoduodenectomy with modified-Child reconstruction for pancreatic cancer 3 years prior, and no recurrence was noted on follow-up. He was admitted to our hospital owing to fever and general fatigue. PLA and septic shock were diagnosed, and conservative therapy with antibiotics was initiated. His general condition gradually improved, but a thrombus in the middle hepatic vein and IVC was noted on follow-up computed tomography on hospital day 8. Although anticoagulant therapy using heparin was started, the thrombus size increase and extended to the right atrium. Considering the risk of pulmonary embolism, we planned a surgical intervention with a cardiovascular surgeon to remove the thrombus. During surgery, we made an incision in the right atrium and removed the thrombus using extracorporeal circulation. After removal, we dissected the middle hepatic vein using an automated suturing device to prevent the thrombus from extending into the IVC. The patient was discharged 10 weeks after surgery. Eighteen months post-intervention, there was no recurrence of either PLA or thrombi. Our experience suggests that physicians should consider the existence of a middle hepatic vein and IVC thrombi when examining PLA patients and that surgical intervention can be applied successfully in such cases.

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