[Surgical Case of Bronchial Mucoepidermoid Carcinoma Safely Diagnosed by Enucleation Under the Bronchoscopy After Bronchial Arterial Embolization].

A 28-year-old male presented to our hospital with hemoptysis and his chest computerized tomography (CT) showed the right middle and lower lobe atelectasis due to the tumor of right intermediate bronchial trunk. To reduce the blood flow to the tumor, bronchial arterial embolization was performed and the tumor was resected using Cryoprobe with a flexible endobronchial scope. Thus, we could observe the tumor localization and diagnose before the surgical procedure. We performed the right sleeve middle lobectomy and the right lower lobe was safely preserved.

PD-1 expression on peripheral blood T-cell subsets correlates with prognosis in non-small cell lung cancer.

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.

Randomized phase II study of daily versus alternate-day administrations of S-1 for the elderly patients with completely resected pathological stage IA (tumor diameter > 2 cm)-IIIA of non-small cell lung cancer: Setouchi Lung Cancer Group Study 1201.

BACKGROUND: It is shown that the postoperative adjuvant chemotherapy for non-small cell lung cancer (NSCLC) was associated with survival benefit in an elderly population. We aimed to analyze the feasibility and efficacy of alternate-day S-1, an oral fluoropyrimidine, for adjuvant chemotherapy in elderly patients with completely resected pathological stage IA (tumor diameter > 2 cm) to IIIA (UICC TNM Classification of Malignant Tumours, 7th edition) NSCLC. METHODS: Elderly patients were randomly assigned to receive adjuvant chemotherapy for one year consisting of either alternate-day oral administration of S-1 (80 mg/m2/day) for 4 days a week (Arm A) or a daily oral administration of S-1 (80 mg/m2/day) for 14 consecutive days followed by 7-day rest (Arm B). The primary endpoint was feasibility (treatment completion rate), which was defined as the proportion of patients who completed the allocated intervention for 6 months with a relative dose intensity (RDI) of 70% or more. RESULTS: We enrolled 101 patients in which 97 patients received S-1 treatment. The treatment completion rate at 6 months was 69.4% in Arm A and 64.6% in Arm B (p = 0.67). Treatment completion rate in Arm B tended to be lower compared to Arm A, as the treatment period becomes longer (at 9 and 12 months). RDI of S-1 at 12 months and completion of S-1 administration without dose reduction or postponement at 12 months was significantly better in Arm A than in Arm B (p = 0.026 and p < 0.001, respectively). Among adverse events, anorexia, skin symptoms and lacrimation of any grade were significantly more frequent in Arm B compared with Arm A (p = 0.0036, 0.023 and 0.031, respectively). The 5-year recurrence-free survival rates were 56.9% and 65.7% for Arm A and B, respectively (p = 0.22). The 5-year overall survival rates were 68.6% and 82.0% for Arm A and B, respectively (p = 0.11). CONCLUSION: Although several adverse effects were less frequent in Arm A, both alternate-day and daily oral administrations of S-1 were demonstrated to be feasible in elderly patients with completely resected NSCLC. TRIAL REGISTRATION: Unique ID issued by UMIN: UMIN000007819 (Date of registration: Apr 25, 2012) https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000009128. Trial ID issued by jRCT: jRCTs061180089 (Date of registration: Mar 22, 2019, for a shift toward a "specified clinical trial" based on Clinical Trials Act in Japan) https://jrct.niph.go.jp/en-latest-detail/jRCTs061180089.

Immunological evaluation of personalized peptide vaccination in refractory small cell lung cancer.

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.

[Current status and prospects of cancer vaccine therapy].

Cancer vaccine is proceeding to a promising therapy against cancer since 1990 when expression cloning method of tumor associated antigens was reported. Clinical trials showed immunological therapies contribute to prolonged survival in patients with cancers, such as prostate cancer and melanoma, so that FDA approved a dendritic cell vaccine in USA, and peptide vaccines are developing energetically in recent years in Japan. Peptide vaccines have advantages immunologically and economically as a cancer vaccine spreads all over the world, because CTL epitope peptides of tumor associate antigen has a highly antigen-specificity, and can be synthesized uniformly in large quantities for easy handing agents. However it has weak points, such as limited effectiveness in clinical responses due to cancer cells escaped from cancer immunity and possibility of unfavorable immune responses. For development of cancer peptide vaccines, biomarkers related with clinical effects and methods to measure favorable and unfavorable immune responses are necessary about vaccine alone and combination with multidisciplinary modalities in large scale phase III studies.

Single nucleotide polymorphisms of the haptoglobin gene in non-small cell lung cancer treated with personalized peptide vaccination.

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.

Feasibility Study of Personalized Peptide Vaccination for Advanced Small Cell Lung Cancer.

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.

Adenoviral gene transduction of hepatocyte growth factor elicits inhibitory effects for hepatoma.

Hepatocyte growth factor (HGF) gene therapy may have potential for treating chronic hepatitis (CH) and liver cirrhosis (LC). However, the lack of an HGF gene therapy study on hepatomas that are often associated with CH or LC, together with the stimulatory effects of HGF on many types of cancer, may hamper its application. This study explored the effects of adenoviral HGF gene transduction and their mechanisms on two types of hepatoma cells (hepatoblastoma and hepatocellular carcinoma) in in vitro experiments. Both types of hepatomas were revealed to have higher adenoviral gene transduction efficiencies and more efficient expressions of the HGF transgene, which successfully activated the HGF receptor/c-Met in an autocrine fashion, than those of other types of cancer. Notably, not only HGF, but also adenoviral infection, inhibited DNA synthesis, whereas only HGF but not adenoviral infection exerted a potent apoptotic effect. Moreover, adenoviral HGF gene transduction additively exerted inhibitory effects on cisplatin-treated hepatomas. In conclusion, inhibitory and apoptotic effects of adenoviral HGF gene transduction in hepatomas in contrast to potent mitogenic and antiapoptotic effects of HGF for hepatocytes are not only of biological interest, but also pose clinical benefits for adenoviral HGF gene therapy for CH and LC.

[A case of advanced breast cancer markedly responding to chemo-endocrine therapy with only slight alopecia].

We report a case of good response to chemo-endocrine therapy with slight alopecia. A 55-year-old woman was diagnosed as advanced breast cancer with T4c, N3, M1, Stage IV, who was left cervical node-positive. She received 4 cycles of CTF (cyclophosphamide 100 mg/body/day 1-14, THP 30 mg/body/days 1,8, and 5-FU 750 mg/body/days 1, 8 4 wq) therapy in addition to oral tamoxifen (20 mg/body) administration. After this treatment, the primary tumor was markedly reduced (PR), and only slight alopecia was observed. Generally, 3 cycles of CAF (CEF) therapy induced severe alopecia (grade 3). But this CTF regimen caused grade 1 alopecia. Most women have strong resistance to alopecia. It seems that the quality of life for breast cancer patients was affected by the extent of the alopecia. Therefore, CTF therapy should be considered effective for advanced breast cancer patients while reducing the extent of alopecia.

Evaluation of prognostic significance of granulocyte-related factors in cancer patients undergoing personalized peptide vaccination.

Since cancer vaccines do not always elicit beneficial effects in treated patients, identification of biomarkers for predicting clinical outcomes would be highly desirable. We previously reported that abnormal granulocytes present in peripheral blood mononuclear cells (PBMC) may contribute to poor prognosis in advanced prostate cancer patients receiving personalized peptide vaccination (PPV). In the current study, we examined whether soluble factors derived from granulocytes, such as matrix metalloproteinase 9 (MMP-9), myeloperoxidase (MPO), and arginase 1 (ARG1), and inhibitory cytokine TGFß in pre-vaccination plasma were useful for predicting prognosis after PPV in advanced cancer patients. In biliary tract cancer (n=25), multivariate Cox regression analysis demonstrated that patients with higher plasma MMP-9 levels had a significantly worse overall survival (OS) [hazard ratio (HR) = 4.637, 95% confidence interval (CI) = 1.670 - 12.877, P = 0.003], whereas MPO, ARG1, or TGFß levels were not correlated with OS. Similarly, patients with higher MMP-9 levels showed worse prognosis than those with lower MMP-9 levels in other types of advanced cancers, including non-small cell lung cancer (n=32, P = 0.037 by log-rank test), and pancreatic cancer (n=41, P = 0.042 by log-rank test). Taken together, plasma MMP-9 levels before vaccination might be potentially useful as a biomarker for selecting advanced cancer patients who would benefit from PPV.

Feasibility study of personalized peptide vaccination for advanced non-small cell lung cancer patients who failed two or more treatment regimens.

The prognosis of non-small cell lung cancer (NSCLC) patients who failed two or more treatment regimens remains very poor. We conducted a phase II study to explore the feasibility of personalized peptide vaccination (PPV), in which peptides are selected and administered based on the pre-existing host immunity before vaccination, as a third or more line treatment in advanced NSCLC patients who failed two or more regimens. Among 57 patients enrolled, 23 or 16 patients received PPV with chemotherapy or targeted therapy, respectively, whereas 18 patients received PPV alone. A maximum of four HLA-matched peptides showing higher peptide-specific IgG responses in pre-vaccination plasma were selected from 31 pooled peptide candidates applicable for patients with HLA-A2, -A24, -A3 supertypes, and/or -A26, followed by subcutaneous administration. No severe adverse events related to PPV were observed. Median survival time was 692, 468, or 226 days in the group of PPV/chemotherapy, PPV/targeted therapy, or PPV alone, respectively. CTL responses to the vaccinated peptides became detectable after vaccination in 58, 50, or 42% of patients in each of these three groups, respectively. In contrast, peptide-specific IgG responses after vaccination augmented in 55, 75, or 62% of patients in each of these groups, respectively. These results suggest the feasibility of PPV for heavily treated advanced NSCLC patients from the view of both immunological responses and safety. Therefore, further evaluation of PPV by prospective randomized trial is warranted for a third or fourth line treatment of advanced NSCLC.

Gene therapy eradicating distant disseminated micro-metastases by optimal cytokine expression in the primary lesion only: novel concepts for successful cytokine gene therapy.

The most serious problem in current gene therapy is that clinical applications have often led to unsatisfactory results. Here we show novel concepts and crucial factors that have been missing for successful cytokine gene therapy. A clinically-relevant mouse model of primary and micro-metastatic osteosarcoma was generated by subcutaneously and intravenously injecting murine osteosarcoma LM8 cells, in which adenoviral gene transduction efficiencies were extremely low; current therapies remain less effective for such disseminated micro-metastases. A single injection of adenoviral vector encoding interleukin-2 gene (Ad.IL-2) was given only into the established primary tumor. Notably, antitumoral immunity was successfully elicited by IL-2 secretion from connective tissues adjacent to the primary tumor, and this immunity not only suppressed primary tumor growth but also eradicated disseminated micro-metastases in distant organs. Most importantly, not only minimal side effects but also maximal therapeutic effects were exerted only in the case of injecting the optimal (i.e., not the highest) dose of Ad.IL-2, because spleen injuries caused by excessive levels of circulating IL-2 might diminish the therapeutic effect. Although the narrow range of the optimal therapeutic expression level of IL-2 may be crucial, it was feasibly determined by serum IL-2 levels. Thus, a crucial factor for successful cytokine gene therapy is not the high gene transduction efficiency in the tumor, which has been generally recommended, but the use of the optimal therapeutic expression level. In conclusion, just a single injection of Ad.IL-2 into a primary tumor lesion, which is feasible, not invasive and cost effective, is potently therapeutic for distant disseminated micro-metastases, as long as the optimal therapeutic level is monitored. These novel concepts, which contradict those of previous studies, warn researches about the possible problems with the ongoing clinical cytokine gene therapy.

Minute lung carcinoma associated with focal honeycombed lesion.

We report a case of minute lung carcinoma that developed in a focal honeycombed lesion in the right lung. A 70-year-old man presented hemosputum, and a cytological examination result was at class IV. A right lower lobectomy of the lung was performed. Microscopically, the thickened alveolar wall revealed tumor cells indicating a minute carcinoma, and showed squamous hyperplasia, metaplasia, and dysplasia, with the carcinoma in the distal airway epithelium. This peripheral lung carcinoma in a focal honeycombed lesion demonstrated the various stages of multistep carcinogenesis, which is recognized in hilar type squamous cell carcinoma. To date, the association between a honeycombed lesion and lung cancer has been poorly described. Here we have presented clear evidence of the association of this carcinoma with the honeycombed lesion.

Outcome for malignant tracheobronchial stenoses in esophageal cancer.

OBJECTIVE: Optimal tracheobronchial stenosis treatment in esophageal cancer remains a clinical challenge. METHODS: Subjects were 26 patients with tracheobronchial stenosis due to esophageal cancer treated by modalities such as expandable metallic stent emplacement, laser therapy, radiotherapy, and/or chemotherapy. We assessed patient outcome and modality efficacy, and determined prognostic factors for survival using multivariate analysis. RESULTS: Of the 26, 16 (61%) had improved respiration after treatment. Average posttreatment survival was 140 days (10-1550 days). Multivariate analysis indicated that a Karnofsky performance score of > or = 70% was the most significant prognostic factor, with chemotherapy and laser therapy also significant factors. CONCLUSIONS: Although individual modalities were effective in ameliorating respiratory symptoms, patients with good performance status survived the longest. After a tracheobronchial stenosis diagnosis in esophageal cancer patients, chemotherapy and laser therapy are recommended if the patient is in good general condition.

Personalized peptide vaccination in patients with refractory non-small cell lung cancer.

Since the prognosis of non-small cell lung cancer (NSCLC) remains poor, the development of novel therapeutic approaches, including cancer vaccines, is highly desirable. In the current study, we conducted a phase II study of personalized peptide vaccination (PPV), in which a maximum of 4 peptides were selected based on pre-existing humoral immune responses and administered subcutaneously (weekly for 6 consecutive weeks and bi-weekly thereafter) in refractory NSCLC patients. Forty-one refractory NSCLC patients (4 stage IIIb, 22 stage IV and 15 recurrent), who had failed to respond to chemotherapy and/or targeted therapy (median number of regimens, 3; median duration, 10 months), were enrolled. Median overall survival (OS) was 304 days with a one-year survival rate of 42% in the enrolled patients. The main toxicity of PPV was skin reactions at the injection sites, but no serious adverse events were observed. In order to identify potential biomarkers for predicting OS, pre-vaccination and post-vaccination clinical findings and laboratory data were retrospectively assessed and evaluated by multivariate Cox regression analysis. Among the pre-vaccination factors examined, high C-reactive protein (CRP) level was a significant predictor of unfavorable OS [hazard ratio (HR)=10.115, 95% confidence interval (CI)=2.447-41.806, P=0.001]. Among the post-vaccination factors, high CRP level and low frequency of CD3⁺CD26⁺ cells were significant predictors of unfavorable OS (HR=23.127, 95% CI=2.919-183.233, P=0.003; HR=0.952, 95% CI=0.917-0.989, P=0.012). Taken together, our results suggest the feasibility of PPV for the treatment of refractory NSCLC. Evaluation of the identified factors before or at an early stage of vaccination could be potentially useful for selecting NSCLC patients who would likely have better prognosis following PPV.

Nuclear Y-box binding protein-1, a predictive marker of prognosis, is correlated with expression of HER2/ErbB2 and HER3/ErbB3 in non-small cell lung cancer.

INTRODUCTION: Nuclear expression of Y-box binding protein-1 (YB-1) is closely associated not only with global drug resistance and expression of several growth factor receptors in various human malignancies but also with overall patient survival. METHODS: The effect of YB-1 knockdown on expression of epidermal growth factor receptor (EGFR) family proteins was examined by Western blot using human lung cancer cell lines. Immunohistochemistry was used to evaluate the expression of nuclear YB-1 and EGFR family proteins in patients with non-small cell lung cancer (NSCLC) (n = 104). RESULTS: In the five NSCLC cell lines, expressions of EGFR, human epidermal growth factor receptor 2 (HER2), HER3, and hepatocyte growth factor receptor (c-Met) in PC-9 cells; of HER2 and c-Met in EBC-1 cells; and of HER3 in QG56 cells were down-regulated by YB-1 knockdown. By immunohistochemical analysis, we observed that HER3 expression was significantly negatively correlated with nuclear YB-1 expression in squamous cell carcinoma (p = 0.038). HER2 expression was positively correlated with nuclear YB-1 expression in adenocarcinoma (p = 0.052). Nuclear expression of YB-1 correlated with overall survival of all patients (p = 0.028) and of patients with adenocarcinoma (p = 0.007). Furthermore, there was a significant difference in therapeutic efficacies of gefitinib between patients with nuclear YB-1 expression and those with non-nuclear YB-1 expression in patients with NSCLC (p = 0.004, n = 26) but not between those with high and those with low expression of EGFR, HER2, HER3, and c-Met. CONCLUSION: Nuclear YB-1 expression might be essential for the malignant phenotype in lung cancer patients and might be an important biomarker for the development of therapeutic strategy against NSCLC.

Focal cholesterol granuloma in the anterior mediastinum: [18F]-fluoro-2-deoxy-D-glucose-positron emission tomography and magnetic resonance imaging findings.

Cholesterol granuloma is a foreign-body type granuloma that forms in reaction to cholesterol crystals. We report a rare case of focal cholesterol granuloma in the anterior mediastinum of a 62-year-old asymptomatic man that presented as an indeterminate anterior mediastinal nodule on [18F]-fluoro-2-deoxy-D-glucose-positron emission tomography and computed tomography scans. T1- and T2-weighted magnetic resonance images revealed markedly hypo-intense signals reflecting pathologic hyalinized collagen fibers. Magnetic resonance signal characteristics might be helpful for distinguishing benign cholesterol granulomas from malignant neoplasms.

Excision repair cross-complementation group 1 predicts progression-free and overall survival in non-small cell lung cancer patients treated with platinum-based chemotherapy.

Expression of excision repair cross-complementation group 1 (ERCC1), p53, or thioredoxin (TRX) is reported to be correlated with resistance to platinum-based drugs. The authors evaluated whether ERCC1, p53, or TRX expression could predict progression-free and/or overall survival in relapsed non-small cell lung cancer (NSCLC) patients treated with platinum-based chemotherapy. Immunohistochemistry was used to examine the expression of these three proteins in resected lung tumor samples obtained from 67 patients treated with platinum-based chemotherapy against recurrent tumors after curative resection. Immunostaining for ERCC1, p53, and TRX was positive in 29, 35, and 24 patients, respectively. Patients negative for ERCC1 had a significantly longer median progression-free (44 vs 26 weeks, P = 0.0075) and overall (73 vs 44 weeks, P = 0.0006) survival than those positive for ERCC1. Patients negative for p53 expression had a significantly longer median overall (70 vs 62 weeks, P = 0.0289), but not progression-free (37.5 vs 36 weeks, P = 0.2465), survival than those positive for p53 expression. From multivariate analysis, negative ERCC1 expression (hazard ratio [HR] = 1.3740, P = 0.0147) was a significantly favorable factor for progression-free survival, and negative ERCC1 expression (HR = 1.6533, P = 0.0018) and better performance status (HR = 1.9117, P = 0.0017) were significantly favorable factors for overall survival. This retrospective study indicates that immunostaining for ERCC1 may be useful for predicting survival in NSCLC patients receiving platinum-based chemotherapy against recurrent tumors after curative resection and can provide critical information for planning personalized chemotherapy.

Expired gas analysis during exercise testing pre-pneumonectomy.

PURPOSE: Expired gas analysis has enabled the successful prediction of postoperative complications in patients undergoing thoracic esophagectomy. We conducted this study to determine whether preoperative expired gas analysis during exercise testing can help identify patients at high risk of postoperative complications after pneumonectomy. METHODS: We measured the vital capacity, percent vital capacity, forced expiratory volume in 1.0 s, percent forced expiratory volume in 1.0 s, maximum oxygen uptake per minute, anaerobic threshold, arterial partial pressure of oxygen, and arterial partial pressure of carbon dioxide in 27 patients scheduled to undergo pneumonectomy. Group A consisted of 18 patients without postoperative cardiopulmonary complications and group B consisted of 9 patients with postoperative cardiopulmonary complications. We compared preoperative cardiopulmonary data between these two groups. RESULTS: Postoperative cardiopulmonary complications developed in 9 of the 27 patients (33.3%), 3 (11%) of whom died. The maximum oxygen uptake and the anaerobic threshold were significantly higher in group A than in group B (P < 0.05), whereas spirometric pulmonary function testing and arterial blood gas analysis showed no intergroup differences. CONCLUSION: Expired gas analysis during exercise testing can help identify patients at high risk of postoperative cardiopulmonary complications after pneumonectomy.

Vasoactive peptides in a pulmonary embolism model.

PURPOSE: To investigate changes in atrial natriuretic peptide (ANP) and angiotensin II (AT-II) levels in a canine model of pulmonary embolism (PE), created by embolizing the left posterior pulmonary artery with gelatin powder. METHODS: Pulmonary arterial pressure (PAP) was measured before, immediately after, and 1 day after pulmonary artery embolization. Plasma ANP and AT-II levels were measured by radioimmunoassay (RIA) before and 1, 3, 7, 14, 21, and 28 days after embolization. ANP and AT-II levels were also measured by RIA in both embolized and nonembolized lung tissue 28 days after embolization. RESULTS: No changes in plasma ANP or AT-II were seen within 28 days after embolization. Although the ANP level in the nonembolized lung tissue was significantly increased, the level in the embolized lung tissue was significantly decreased compared with that of sham-operated control lung tissue. The AT-II level in the nonembolized lung tissue was significantly decreased compared with that of the control lung tissue, but the level in the embolized lung tissue did not change. CONCLUSION: Both ANP and AT-II in the nonembolized lung tissue reacted to compensate for vasoconstriction caused by the PE in this model.