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1.
Immunopharmacol Immunotoxicol ; 43(2): 176-182, 2021 Apr.
Article in English | MEDLINE | ID: mdl-33541161

ABSTRACT

BACKGROUND: Many clinical trials of immune checkpoint blockade-based combination therapies are under way. Vaccine therapy is a promising partner of combination therapies. We have developed a personalized peptide vaccination and conducted clinical trials of it in patients with various cancers. At the present time, we have only a limited number of biomarkers related to the prognosis of vaccine-treated patients. Thus, new biomarkers are urgently needed. METHODS: In this study, we investigated the plasma cell-free DNA (cfDNA) integrity-a ratio of the necrotic tumor cell-derived long cfDNA fragments to the total dead cell-derived short cfDNA fragments from genomic Alu elements-in patients with advanced nonsmall cell lung cancer during treatment with the personalized peptide vaccination. RESULTS: We found that (1) the cfDNA integrity was decreased after the first cycle of vaccination, and (2) the patients with high prevaccination cfDNA integrity survived longer than those with low prevaccination integrity (median survival time (MST): 17.9 versus 9.0 months, respectively; hazard ratio (HR): 0.58, p = .0049). A similar tendency was observed in postvaccination cfDNA integrity (MST: 16.4 vs 9.4 months; HR: 0.65, p = .024). CONCLUSIONS: These results suggest that cfDNA integrity is a possible prognostic biomarker in patients treated with the personalized peptide vaccine.


Subject(s)
Biomarkers, Tumor/blood , Cancer Vaccines/administration & dosage , Carcinoma, Non-Small-Cell Lung/blood , Cell-Free Nucleic Acids/blood , Immunotherapy, Active/trends , Lung Neoplasms/blood , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/mortality , Humans , Immunotherapy, Active/mortality , Lung Neoplasms/drug therapy , Lung Neoplasms/mortality , Prognosis , Survival Rate/trends , Treatment Outcome
2.
BMC Surg ; 17(1): 54, 2017 May 10.
Article in English | MEDLINE | ID: mdl-28486937

ABSTRACT

BACKGROUND: A clear survival benefit has been reported for lung metastasectomy for colorectal cancer, and several clinicopathological prognostic factors have been proposed in the past. However, clinical advances, such as chemotherapy and radiographic imaging, should have improved patient outcome and may have altered prognosticators. This study aimed to assess patient survival and determine prognostic factors for survival and recurrence in patients who underwent initial lung metastasectomy for colorectal cancer in the modern clinical era. METHODS: Clinicopathological data and outcomes of 59 patients who underwent curative initial lung metastasectomy for colorectal cancer from 2004 to 2012 at a single institution in Japan were retrospectively investigated. Survival was estimated using the Kaplan - Meier method, and Cox proportional hazards regression models were used to estimate the prognostic impacts of each variable in univariate and multivariate analysis. RESULTS: The 5-years overall and disease-free survival rates were 54.3 and 40.6%, respectively. A disease-free interval < 24 months after colorectal cancer resection (P = 0.004) and a serum carcinoembryonic antigen ≥ 5.0 ng/mL before initial lung metastasectomy (P = 0.015) were independent predictors for poor overall survival. Moreover, the disease-free interval after colorectal cancer resection < 24 months (P = 0.010) and a colorectal cancer with N2 stage disease (P = 0.018) were independently associated with poor disease-free survival. On the other hand, the number of lung metastasis was not identified as a poor prognostic factor for both overall and disease-free survival. CONCLUSIONS: Our findings demonstrated similar or slightly better overall survival, and substantially favorable disease-free survival as compared with past reports. Poor prognostic factors for overall survival appeared not to differ from those of past studies, although this modern series did not determine the number of lung metastasis as a poor prognostic factor, which should be investigated in future studies. Moreover, initial lung metastasectomy is not expected to be a curable treatment for patients with both a short disease-free survival after colorectal cancer resection and colorectal cancers with N2 stage disease.


Subject(s)
Colorectal Neoplasms/pathology , Lung Neoplasms/surgery , Metastasectomy/methods , Aged , Disease-Free Survival , Female , Humans , Japan , Lung Neoplasms/secondary , Male , Multivariate Analysis , Neoplasm Recurrence, Local/surgery , Pneumonectomy/methods , Prognosis , Proportional Hazards Models , Retrospective Studies , Survival Rate
3.
Kyobu Geka ; 68(11): 944-6, 2015 Nov.
Article in Japanese | MEDLINE | ID: mdl-26469262

ABSTRACT

Computed tomography (CT) guided lung biopsy is a useful examination in diagnosing pulmonary diseases, but the complications such as pneumothorax or pulmonary hemorrhage can not be ignored. Among them, air embolization is a severe complication, although it is infrequently encountered. Forty two-year-old man admitted to our department for the examination of left lung tumor. CT guided lung biopsy was performed. After examination, the patient showed disturbance in cardiac function, which recovered in several minutes. Chest CT revealed air bubble in the left ventricle. After 2-hours head down position followed by bed rest, air bubble is confirmed to be dissappeared by CT.


Subject(s)
Air , Biopsy, Needle/adverse effects , Lung Diseases/pathology , Ventricular Dysfunction, Left/etiology , Adult , Humans , Lung Diseases/surgery , Male , Pneumonectomy , Tomography, X-Ray Computed , Ventricular Dysfunction, Left/diagnostic imaging
4.
Cancer Sci ; 105(10): 1229-35, 2014 Oct.
Article in English | MEDLINE | ID: mdl-25117757

ABSTRACT

PD-1 expression in peripheral blood T-cells has been reported in several kinds of cancers, including lung cancer. However, the relationship between PD-1 expression in peripheral blood T-cells and prognosis after treatment with a cancer vaccine has not been reported. To elucidate this relationship, we analyzed PD-1 expression in the peripheral blood T-cells of patients with non-small cell lung cancer. The blood samples used in this study were obtained from patients enrolled in phase II clinical trials of a personalized peptide vaccine. Seventy-eight samples obtained before and after a single vaccination cycle (consisting of six or eight doses) were subjected to the analysis. PD-1 was expressed on lymphocytes in the majority of samples. The relative contents of PD1(+) CD4(+) T-cells against total lymphocytes before and after the vaccination cycle correlated with overall survival (OS) with a high degree of statistical significance (P < 0.0001 and P = 0.0014). A decrease in PD-1(+) CD8(+) T-cells after one cycle of vaccination also correlated with longer OS (P = 0.032). The IgG response to the non-vaccinated peptides suggested that the epitope spreading seemed to occur more frequently in high-PD-1(+) CD4(+) T-cell groups. Enrichment of CD45RA(-) CCR7(-) effector-memory phenotype cells in PD-1(+) T-cells in PBMCs was also shown. These results suggest that PD-1 expression on the peripheral blood T-cell subsets can become a new prognostic marker in non-small cell lung cancer patients treated with personalized peptide vaccination.


Subject(s)
Carcinoma, Non-Small-Cell Lung/immunology , Lung Neoplasms/immunology , Programmed Cell Death 1 Receptor/blood , T-Lymphocyte Subsets/chemistry , Adult , Aged , Aged, 80 and over , Carcinoma, Non-Small-Cell Lung/mortality , Carcinoma, Non-Small-Cell Lung/therapy , Female , Humans , Immunoglobulin G/blood , Immunologic Memory , Interferon-gamma/biosynthesis , Lung Neoplasms/mortality , Lung Neoplasms/therapy , Male , Middle Aged , Prognosis , T-Lymphocytes, Cytotoxic/immunology
5.
Kurume Med J ; 68(3.4): 183-189, 2023 Sep 25.
Article in English | MEDLINE | ID: mdl-37316291

ABSTRACT

BACKGROUND: Preoperative computed tomography-guided marking can help identify small non-palpable pulmonary nodules during surgery. However, this technique is associated with the risk of air embolism. We retrospectively evaluated whether small pulmonary nodules could be intraoperatively localized using cone-beam computed tomography (CBCT). METHODS: A hybrid operating room permitting stable lateral positioning and scanning from the pulmonary apex to the base was used in all patients. CBCT images were obtained using a 10-s protocol with 180º rotation of the C-arm flat panel detector around the patient. Clips were placed on the visceral pleura to help guide pulmonary nodule localization. Partial pulmonary resection was performed using video-assisted thoracoscopic surgery at the predicted nodule site. RESULTS: Between July 2013 and June 2019, 132 patients with 145 lesions underwent this procedure at our center. The detection rate of lesions on CBCT was 100%. The pathological diagnoses were primary lung cancer, metastatic pulmonary tumors, and benign lesions. The average consolidation-to-tumor ratio was 0.65 for all nodules, with ratios of 0.33, 0.96, and 0.70 for primary lung cancer, metastatic pulmonary tumors, and benign lesions, respectively. No complications related to this localization method were observed. CONCLUSIONS: CBCT-guided intraoperative localization is safe and feasible for non-palpable small pulmonary nodules. This technique may eliminate the risk of serious complications such as air embolism.


Subject(s)
Embolism, Air , Lung Neoplasms , Multiple Pulmonary Nodules , Humans , Retrospective Studies , Multiple Pulmonary Nodules/diagnostic imaging , Multiple Pulmonary Nodules/surgery , Lung Neoplasms/diagnostic imaging , Lung Neoplasms/surgery , Cone-Beam Computed Tomography , Surgical Instruments
6.
Cancer Sci ; 103(4): 638-44, 2012 Apr.
Article in English | MEDLINE | ID: mdl-22321067

ABSTRACT

Since the prognosis of small cell lung cancer (SCLC) remains poor, development of new therapeutic approaches, including immunotherapies, would be desirable. In the current study, to evaluate immunological responses in refractory SCLC patients, we conducted a small scale phase II clinical trial of personalized peptide vaccination (PPV), in which vaccine antigens are selected based on pre-existing host immunity. Ten refractory SCLC patients, who had failed to respond to chemo- and/or chemoradiotherapies (median number of regimens, 2.5; median duration, 20.5 months), were enrolled. A maximum of four human leukocyte antigen (HLA)-matched peptides showing higher antigen-specific humoral responses were subcutaneously administered (weekly for six consecutive weeks and then bi-weekly thereafter). PPV was terminated before the 3rd administration in four patients because of rapid disease progression, whereas the remaining six patients completed at least one cycle (six times) of vaccinations. Peptide-specific immunological boosting was observed in all of the six patients at the end of the first cycle of vaccinations, with their survival time of 25, 24.5 (alive), 10 (alive), 9.5, 6.5, and 6 months. Number of previous chemotherapy regimens and frequency of CD3(+) CD26(+) cells in peripheral blood were potentially prognostic in the vaccinated patients (hazard ratio [HR] = 2.540, 95% confidence interval [CI] = 1.188-5.431, P = 0.016; HR = 0.941, 95% CI = 0.878-1.008, P = 0.084; respectively). Based on the feasible immune responses in refractory SCLC patients who received at least one cycle (six times) of vaccinations, PPV could be recommended for a next stage of larger-scale, prospective clinical trials.


Subject(s)
Cancer Vaccines/immunology , Lung Neoplasms/therapy , Small Cell Lung Carcinoma/therapy , Vaccines, Subunit/immunology , Aged , CD3 Complex , Cancer Vaccines/adverse effects , Cancer Vaccines/therapeutic use , Dipeptidyl Peptidase 4 , Humans , Lymphocyte Subsets/immunology , Lymphocytes, Tumor-Infiltrating/immunology , Male , Middle Aged , Vaccines, Subunit/therapeutic use
7.
Mol Clin Oncol ; 16(6): 112, 2022 Jun.
Article in English | MEDLINE | ID: mdl-35620212

ABSTRACT

The present study aimed to clarify the humoral and cellular immune responses of patients with cancer who experienced no recurrence over a long term after receiving a cancer vaccine. The immune kinetics were investigated in response to a personalized peptide vaccination (PPV) among 44 Japanese patients without an active tumor at entry to the vaccination: Lung adenocarcinoma (n=11); colon (n=18); and breast cancer (n=15) (9, 10, 12, 8 and 5 patients with stage I, II, III and IV recurrences, respectively). The patients' immunoglobulin G (IgG) and cytotoxic T lymphocyte (CTL) activities were measured using a multiplexed Luminex assay and an interferon-γ release assay, respectively. There were no severe adverse events related to the PPV other than a grade III injection site reaction. A potent boost in IgG or CTL at the end of the 1st vaccination cycle was observed in 77% of the patients (n=84). The IgG levels were sustained throughout the follow-up period, whereas the CTL levels declined and were transient. A total of 37 of the 44 patients (84%) had no recurrence, with a median follow-up of 67.6 months (interquartile range, 45.6-82.8 months). Overall, the PPV induced long-term humoral immunity with transient cellular immunity in the majority of patients with cancer without an active tumor at their entry to the PPV.

8.
Surg Today ; 41(6): 780-6, 2011 Jun.
Article in English | MEDLINE | ID: mdl-21626322

ABSTRACT

PURPOSE: We previously demonstrated in a pilot study that postoperative cardiopulmonary complications could be reduced by selecting pulmonary resection procedures based on the results of a combination of specific preoperative cardiopulmonary function tests. The present study reports a re-examination of the criteria for preoperative screening and prospectively assessed whether the selected surgical procedures were appropriate in 200 patients who underwent the planned extent of pulmonary resection. METHODS: In 200 patients requiring lung tumor resection, five preoperative parameters (forced expiratory volume in 1 s on the intact side, maximal oxygen uptake, ejection fraction, occluded pulmonary artery pressure, and occluded total pulmonary vascular resistance index) were used to assign each patient to one of five risk categories in order to select the optimal resection procedure. Thereafter, the postoperative course was investigated to determine the value of this selection method. RESULTS: Thoracotomy was performed in 195 of the 200 patients (97.5%). Two patients (1%) died; one patient succumbed to acute exacerbation of interstitial pneumonia and the other patient died from pulmonary embolism. Six patients (3.1%) developed major complications after surgery and 12 patients (6.2%) had mild complications, while 175 (89.7%) showed a good postoperative course. CONCLUSION: The use of five preoperative parameters to select the pulmonary resection procedure minimized postoperative death and major complications.


Subject(s)
Heart Function Tests , Lung Neoplasms/surgery , Pneumonectomy/adverse effects , Respiratory Function Tests , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Postoperative Complications/prevention & control , Predictive Value of Tests , Preoperative Care , Risk Assessment
9.
Surg Today ; 41(1): 111-4, 2011 Jan.
Article in English | MEDLINE | ID: mdl-21191701

ABSTRACT

PURPOSE: To define the changes in the pleural cavity after pleurodesis induced by talc or OK-432. METHODS: A total of 30 rats were divided into three groups: a normal saline group (control group, n = 10), a group administered 400 mg/kg talc (talc group, n = 10), and a group administered 0.3 KE/kg OK-432 (OK-432 group, n = 10). Pleural cavities were examined and scored on the 30th day after the intrapleural administration of each agent. RESULTS: Both the talc group and OK-432 group showed significantly higher macroscopic or microscopic pleurodesis scores than the control group (P < 0.05). Upon microscopic evaluation, the pleurodesis scores in the talc group were significantly higher than those in the OK-432 group (P < 0.01).The majority of the pleural thickness was found on the visceral pleura, and the parietal pleura was very thin. The thickness of the visceral pleura in the talc group was significantly higher than that in the OK-432 group (P < 0.005). Pathologically, the pleural thickening in the talc group consisted of fibrous tissue with injury of the pleural mesothelium, and talc particles were seen in the submesothelial fibrotic tissue and inside the alveoli. CONCLUSIONS: Talc pleurodesis induces more marked changes in the pleural cavity than OK-432-induced pleurodesis.


Subject(s)
Antineoplastic Agents/pharmacology , Antiperspirants/pharmacology , Picibanil/pharmacology , Pleural Cavity/drug effects , Pleurodesis , Talc/pharmacology , Animals , Male , Pleura/drug effects , Pleura/pathology , Pleural Cavity/pathology , Rats , Rats, Wistar
10.
Surg Today ; 41(9): 1228-33, 2011 Sep.
Article in English | MEDLINE | ID: mdl-21874420

ABSTRACT

PURPOSE: We attempted to identify the factors related to an early restoration of the exercise capacity after lung resection. METHODS: Major lung resection was performed in 164 patients. Exercise testing and spirometry were performed before surgery, and 2 weeks and 1 month afterward. During exercise, the maximum oxygen uptake per minute per m(2) of body surface area (VO(2)max/m(2)) was measured. The percent change of VO(2)max/m(2) at 2 weeks and 1 month after surgery was calculated by setting the preoperative VO(2)max/m(2) value as 100%. Patients were then assigned to the early restoration group or late restoration group according to their VO(2)max/m(2) measured 2 weeks after surgery. Preoperative cardiopulmonary function, as well as various preoperative and intraoperative factors were compared between the two groups. RESULTS: At 2 weeks after surgery, the mean VO(2)max/m(2) was 80.9% compared with that before surgery, and was 88.1% at 1 month. A multivariate analysis showed that the surgical method used (thoracotomy and mediastinal lymph node dissection) had a significant effect on the postoperative restoration of the VO(2)max/m(2). CONCLUSION: An early restoration of exercise capacity after lung resection is possible in patients without mediastinal lymph node dissection and in those who have a small thoracotomy wound.


Subject(s)
Exercise Tolerance , Lung Neoplasms/surgery , Oxygen Consumption , Pneumonectomy/rehabilitation , Recovery of Function/physiology , Adult , Aged , Aged, 80 and over , Exercise Test , Female , Humans , Logistic Models , Lymph Node Excision , Male , Mediastinum , Middle Aged , Multivariate Analysis , Pneumonectomy/methods , Retrospective Studies , Spirometry , Thoracotomy
11.
J Anus Rectum Colon ; 4(3): 151-155, 2020.
Article in English | MEDLINE | ID: mdl-32743118

ABSTRACT

Myxofibrosarcoma is a soft tissue sarcoma that occurs in elderly patients. Primary myxofibrosarcoma rarely arises in the mesentery; this is the fourth known case of myxofibrosarcoma presenting as a mesenteric tumor. A 62-year-old male with a mesenteric myxofibrosarcoma presented with an abdominal mass; his symptoms were frequent urination and a sense of abdominal pressure. He was admitted for further examination. Computed tomography (CT) and magnetic resonance imaging (MRI) revealed a mesenteric lesion. The preoperative diagnosis was a suspected malignant myxoid tumor. We performed a curative resection with wide margins. The histopathological and immunohistochemical findings confirmed that the tumor was mesenteric myxofibrosarcoma. The postoperative course was uneventful, and there have been no signs of relapse for three years to date after surgery. It is difficult to make a definitive diagnosis of mesenteric myxofibrosarcoma using only CT or MRI. However, when the preoperative findings suggest a malignant mesenteric tumor, then the best practice is resection with sufficient margins.

12.
Int J Oncol ; 56(6): 1479-1489, 2020 06.
Article in English | MEDLINE | ID: mdl-32236612

ABSTRACT

Peptide­based cancer vaccines have failed to provide sufficient clinical benefits in order to be approved in clinical trials since the 1990s. To understand the mechanisms underlying this failure, the present study investigated biomarkers associated with the lower overall survival (OS) among 2,588 patients receiving personalized peptide vaccination (PPV). Survival data were obtained from a database of 2,588 cancer patients including 399 patients with lung, 354 with prostate and 344 with colon cancer. They entered into phase II clinical trials of PPV in which 2 to 4 of 31 warehouse peptides were selected for vaccination on an individual patient basis based on human leukocyte antigen (HLA) class IA­types and pre­existing peptide­specific IgG levels. Higher pre­vaccination neutrophil, monocyte and platelet counts, and lower pre­vaccination lymphocyte and red blood cell counts were inversely associated with OS, with higher sensitivities in the proportions of neutrophils and lymphocytes, respectively. The most potent unfavorable and favorable factors for OS were the median percentage of neutrophils (≥64.8%) or percentage of lymphocytes (≥25.1%) with correlation coefficients (R2) of 0.98 and 0.92, respectively. Higher pre­vaccination levels of c­reactive protein and other inflammatory soluble factors were inversely associated with OS. Pre­vaccination peptide­specific immunity levels had no effect on OS, although lower immune boosting levels were inversely associated with OS. None of the 31 peptides was inversely associated with OS, although a few peptides were positively associated with it. On the whole, the findings of the present study suggested that pre­vaccination inflammatory signatures, but not those of post­vaccination immune induction, were associated with lower clinical benefits of PPV.


Subject(s)
Biomarkers, Tumor/immunology , C-Reactive Protein/metabolism , Neoplasms/drug therapy , Vaccines, Subunit/therapeutic use , Aged , Cancer Vaccines/immunology , Cancer Vaccines/therapeutic use , Clinical Trials, Phase II as Topic , Databases, Factual , Female , Humans , Male , Middle Aged , Monocytes/metabolism , Neoplasms/blood , Neoplasms/immunology , Neutrophils/metabolism , Platelet Count , Precision Medicine , Survival Analysis , Treatment Outcome , Vaccines, Subunit/immunology
13.
Int J Surg Case Rep ; 64: 157-160, 2019.
Article in English | MEDLINE | ID: mdl-31655288

ABSTRACT

INTRODUCTION: When the management of an anterior mediastinal tumor requires general anesthesia, airway narrowing and obstruction may occur secondary to muscle relaxation. PRESENTATION OF CASES: Two men (ages, 15 and 36 years) presented with a giant anterior mediastinal tumor and central airway obstruction. We used Dumon stents to effectively secure the airway in both patients. After chemotherapy, stent removal was safely performed in each case because the tumor was substantially smaller. DISCUSSION: Dumon stents effectively secured the airway. These stents were easily removed after chemotherapy without severe complications. CONCLUSION: Temporary stenting is useful in patients with a giant anterior mediastinal tumor who require general anesthesia.

14.
Respirol Case Rep ; 6(7): e00358, 2018 Oct.
Article in English | MEDLINE | ID: mdl-30202526

ABSTRACT

Extramedullary haematopoiesis is a rare disease that is usually associated with haematologic disorders such as thalassemia, myelodysplastic syndrome, and hereditary spherocytosis. It frequently occurs in the liver, spleen, and lymph nodes. Rarely, it occurs in the posterior mediastinum. We report the case of a 59-year-old man with lateral posterior mediastinal masses that were incidentally detected during treatment for hereditary spherocytosis. We performed video-assisted thoracic surgery to confirm the diagnosis and differentiate the masses from neurogenic tumours and other posterior mediastinal diseases. The pathological findings were consistent with intrathoracic extramedullary haematopoiesis. Although extramedullary haematopoiesis can be managed without interventions, surgery may be required in some cases. In such cases, video-assisted thoracoscopic surgery is advised because it is a useful and less invasive procedure.

15.
J Thorac Dis ; 10(5): 2916-2923, 2018 May.
Article in English | MEDLINE | ID: mdl-29997957

ABSTRACT

BACKGROUND: Lung function in the late postoperative phase after pulmonary lobectomy is insufficiently characterized. This study aimed to appraise lung function in the late postoperative phase according to vital capacity (VC) and forced expiratory volume in 1 second (FEV1) in patients who underwent pulmonary lobectomy. METHODS: Pre- and postoperative VC and FEV1 were reviewed in 112 patients who underwent pulmonary lobectomy. Postoperative lung volume was assessed >1 year after surgery. Postoperative decreases in VC and FEV1 were compared with preoperative predicted values among patients who underwent resection of specific lobe. Determinants effecting a decrease in lung function were also investigated. RESULTS: A mean postoperative decreased VC of 10.5%±1.8% was recorded in patients who underwent right upper lobectomy (RU), 7.2%±1.5% for right middle lobectomy (RM), 14.3%±2.3% for right lower lobectomy (RL), 16.6%±3.0% for left upper lobectomy (LU), and 14.7%±2.5% for left lower lobectomy (LL). Corresponding FEV1 values were 14.8%±1.8% for RU, 11.9%±4.0% for RM, 14.9%±2.3% for RL, 17.9%±2.9% for LU, and 15.1%±2.4% for LL. The actual decreasing rate of VC was overestimated in patients who underwent RU, RL, LU, and LL. In contrast, FEV1 was overestimated only in patients who underwent RL and LL. Patients with chronic obstructive pulmonary disease (COPD) exhibited significantly better preservation of FEV1. CONCLUSIONS: Patients scheduled for RL and LL, or those with COPD, appeared to exhibit preserved lung function in the late postoperative phase after pulmonary lobectomy.

16.
Kurume Med J ; 64(1.2): 13-20, 2018 Feb 26.
Article in English | MEDLINE | ID: mdl-29176296

ABSTRACT

Periostin is an extracellular matrix N-glycoprotein that is a major constituent of the desmoplastic stroma around solid tumors. Periostin promotes tumor invasion and metastasis via epithelial-mesenchymal transition. The aims of this study were to evaluate periostin expression immunohistochemically and quantitatively in patients with non-small cell lung cancer (NSCLC) and to assess any associations with clinical features and prognosis. A total of 184 specimens of NSCLC tissue were investigated, including 134 adenocarcinomas, 39 squamous cell carcinomas, and 11 other histologic subtypes. The intra-tumoral periostin expression area in each captured field was calculated using the image processing integration software WinROOF. The mean periostin expression score was classified as high or low by the median value of its expression area. Univariate analysis demonstrated that gender, tumor size, T status, N status, stage, histologic type, smoking habits, percent vital capacity, 1% forced expiratory volume, and pleural invasion were each significantly associated with periostin scores. Multivariate analysis revealed that high periostin expression score was an independent prognostic factor significantly associated with decreased cancer-specific survival (HR, 3.65; 95% CI, 1.04-12.84; P=0.0439). We concluded that intratumoral periostin expression was an independent prognostic factor for NSCLC.


Subject(s)
Carcinoma, Non-Small-Cell Lung/chemistry , Cell Adhesion Molecules/analysis , Lung Neoplasms/chemistry , Adult , Aged , Aged, 80 and over , Carcinoma, Non-Small-Cell Lung/mortality , Carcinoma, Non-Small-Cell Lung/pathology , Female , Humans , Lung Neoplasms/mortality , Lung Neoplasms/pathology , Male , Middle Aged , Neoplasm Staging , Prognosis
17.
Oncol Lett ; 13(2): 993-999, 2017 Feb.
Article in English | MEDLINE | ID: mdl-28356990

ABSTRACT

The present study analyzed polymorphisms of the 5' flanking region (from nt -840 to +151) of the haptoglobin gene in 120 patients with advanced non-small cell lung cancer (NSCLC) receiving personalized peptide vaccinations. In the region, six single nucleotide polymorphisms (SNPs) were confirmed, of which two, rs5472 and rs9927981, were completely linked to each other. The minor allele frequencies of rs5472/rs9927981 and rs4788458 were higher than those of the other three SNPs. The genotype frequencies of rs5472 or rs9927981 were A/A or C/C (42.5%, n=51), A/G or C/T (40.8%, n=49), and G/G or T/T (16.7%, n=20), respectively; and those of rs4788458 were T/T (34.2%, n=41), T/C (40.0%, n=48), and C/C (25.8%, n=31). The association between polymorphism rs5472/rs9927981 and prognosis, or between rs4788458 and prognosis, was analyzed further. However, no correlation was found between these SNPs and overall survival, regardless of subgroup analysis of gender, histology or concurrent therapy. These results suggest that the polymorphisms rs5472/rs9927981 and rs4788458 are not useful prognostic tools for patients with NSCLC treated with personalized peptide vaccination.

18.
Clin Lung Cancer ; 18(6): e385-e394, 2017 11.
Article in English | MEDLINE | ID: mdl-28416261

ABSTRACT

INTRODUCTION: The prognosis of patients with small cell lung cancer (SCLC) remains very poor. Therefore, the development of new therapeutic approaches, including immunotherapies, is desirable. PATIENTS AND METHODS: We conducted a phase II study of personalized peptide vaccination (PPV), in which a maximum of 4 human leukocyte antigen-matched peptides were selected from 31 pooled peptides according to the pre-existing peptide-specific IgG responses before vaccination. The PPV was subcutaneously administered. RESULTS: Forty-six patients were enrolled (median age, 63 years; 40 patients were men). Grade 1 (n = 13), 2 (n = 10), or 3 (n = 1) skin reactions at the injection sites were observed; however, no other severe adverse events related to the PPV were observed. The median survival time was 466, 397, 401, and 107 days in the subgroups with 0 (n = 5), 1 (n = 15), 2 (n = 12), and ≥ 3 (n = 14) previous chemotherapy regimens, respectively. Peptide-specific IgG responses to the vaccinated peptides were augmented in 70% and 95% of patients after 1 and 2 vaccination cycles, respectively. The overall survival (OS) of patients with augmented IgG responses to a greater number of nonvaccinated peptides after the second cycle of vaccination was significantly longer (median survival time, 1237 days vs. 382 days; P = .010). In addition, augmentation of IgG responses specific to 6 peptides, including Lck-derived peptides, was significantly related to better OS (P < .05, in each peptide). CONCLUSION: These results suggest the feasibility of PPV for SCLC patients from the viewpoints of safety, immune boosting, and possible prolongation of OS. Therefore, further evaluation of PPV for advanced SCLC in prospective randomized trials is warranted.


Subject(s)
Cancer Vaccines/administration & dosage , Immunotherapy/methods , Lung Neoplasms/therapy , Peptides/administration & dosage , Small Cell Lung Carcinoma/therapy , Adult , Aged , Aged, 80 and over , Cancer Vaccines/immunology , Feasibility Studies , Female , Humans , Immunoglobulin G/immunology , Injections, Subcutaneous , Lung Neoplasms/immunology , Male , Middle Aged , Peptides/immunology , Precision Medicine , Prognosis , Small Cell Lung Carcinoma/immunology , Survival Rate
19.
Interact Cardiovasc Thorac Surg ; 23(4): 548-52, 2016 10.
Article in English | MEDLINE | ID: mdl-27324730

ABSTRACT

OBJECTIVES: Dividing the intersegmental planes with a stapler during pulmonary segmentectomy leads to volume loss in the remnant segment. The aim of this study was to assess the influence of segment division methods on preserved lung volume and pulmonary function after segmentectomy. METHODS: Using image analysis software on computed tomography (CT) images of 41 patients, the ratio of remnant segment and ipsilateral lung volume to their preoperative values (R-seg and R-ips) was calculated. The ratio of postoperative actual forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) per those predicted values based on three-dimensional volumetry (R-FEV1 and R-FVC) was also calculated. Differences in actual/predicted ratios of lung volume and pulmonary function for each of the division methods were analysed. We also investigated the correlations of the actual/predicted ratio of remnant lung volume with that of postoperative pulmonary function. RESULTS: The intersegmental planes were divided by either electrocautery or with a stapler in 22 patients and with a stapler alone in 19 patients. Mean values of R-seg and R-ips were 82.7 (37.9-140.2) and 104.9 (77.5-129.2)%, respectively. The mean values of R-FEV1 and R-FVC were 103.9 (83.7-135.1) and 103.4 (82.2-125.1)%, respectively. There were no correlations between the actual/predicted ratio of remnant lung volume and pulmonary function based on the division method. Both R-FEV1 and R-FVC were correlated not with R-seg, but with R-ips. CONCLUSIONS: Stapling does not lead to less preserved volume or function than electrocautery in the division of the intersegmental planes.


Subject(s)
Electrocoagulation , Lung Neoplasms/physiopathology , Lung Neoplasms/surgery , Mastectomy, Segmental , Pneumonectomy , Surgical Stapling , Aged , Female , Forced Expiratory Volume , Humans , Imaging, Three-Dimensional , Lung Neoplasms/diagnostic imaging , Lung Volume Measurements , Male , Middle Aged , Retrospective Studies , Tomography, X-Ray Computed
20.
Ann Thorac Surg ; 100(6): 2339-40, 2015 Dec.
Article in English | MEDLINE | ID: mdl-26652527

ABSTRACT

A 48-year-old woman with a 3-month history of back pain was admitted for further examination of multiple left pleural nodules. She had undergone bilateral breast augmentation with silicone implants 10 years previously. Nine years after the operation, both ruptured implants were removed, and autologous fat was injected. Computed tomography revealed multiple pleural nodules suggestive of malignant pleural mesothelioma. Thoracoscopic exploration revealed multiple pleural nodules with massive pleural adhesions. The nodules were filled with viscous liquid and were histologically determined to be siliconomas. Disseminated pleural siliconoma should be recognized as a late adverse event of silicone breast implantation.


Subject(s)
Breast Implants/adverse effects , Foreign-Body Migration/diagnosis , Lung Neoplasms/diagnosis , Mesothelioma/diagnosis , Pleural Neoplasms/diagnosis , Silicone Gels/adverse effects , Diagnosis, Differential , Female , Humans , Mammaplasty , Mesothelioma, Malignant , Middle Aged
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