Rapid imaging of thymoma and thymic carcinoma with a fluorogenic probe targeting γ-glutamyltranspeptidase.

In recent years, thoracoscopic and robotic surgical procedures have increasingly replaced median sternotomy for thymoma and thymic carcinoma. In cases of partial thymectomy, the prognosis is greatly improved by ensuring a sufficient margin from the tumor, and therefore intraoperative fluorescent imaging of the tumor is especially valuable in thoracoscopic and robotic surgery, where tactile information is not available. γ-Glutamyl hydroxymethyl rhodamine green (gGlu-HMRG) has been applied for fluorescence imaging of some types of tumors in the resected tissues, and here we aimed to examine its validity for the imaging of thymoma and thymic carcinoma. 22 patients with thymoma or thymic carcinoma who underwent surgery between February 2013 and January 2021 were included in the study. Ex vivo imaging of specimens was performed, and the sensitivity and specificity of gGlu-HMRG were 77.3% and 100%, respectively. Immunohistochemistry (IHC) staining was performed to confirm expression of gGlu-HMRG's target enzyme, γ-glutamyltranspeptidase (GGT). IHC revealed high GGT expression in thymoma and thymic carcinoma in contrast to absent or low expression in normal thymic parenchyma and fat tissue. These results suggest the utility of gGlu-HMRG as a fluorescence probe for intraoperative visualization of thymomas and thymic carcinomas.

Immune checkpoint inhibitors for solid organ transplant recipients: clinical updates.

Transplant care continues to advance with increasing clinical experience and improvements in immunosuppressive therapy. As the population ages and long-term survival improves, transplant patient care has become more complex due to comorbidities, frailty, and the increased prevalence of cancer posttransplantation. Immune checkpoint inhibitors (ICIs) have become a standard treatment option for many cancers in non-transplant patients, but the use of ICIs in transplant patients is challenging due to the possibility of disrupting immune tolerance. However, over the past few years, ICIs have gradually started to be used in transplant patients as well. In this study, we review the current use of ICIs after all solid organ transplantation procedures (kidney, liver, heart, and lung). Increasing data suggest that the type and number of immunosuppressants may affect the risk of rejection after immunotherapy. Immunotherapy for cancer in transplant patients may be a feasible option for selected patients; however, prospective trials in specific organ transplant recipients are needed.

Rapid imaging of lung cancer using a red fluorescent probe to detect dipeptidyl peptidase 4 and puromycin-sensitive aminopeptidase activities.

Rapid identification of lung-cancer micro-lesions is becoming increasingly important to improve the outcome of surgery by accurately defining the tumor/normal tissue margins and detecting tiny tumors, especially for patients with low lung function and early-stage cancer. The purpose of this study is to select and validate the best red fluorescent probe for rapid diagnosis of lung cancer by screening a library of 400 red fluorescent probes based on 2-methyl silicon rhodamine (2MeSiR) as the fluorescent scaffold, as well as to identify the target enzymes that activate the selected probe, and to confirm their expression in cancer cells. The selected probe, glutamine-alanine-2-methyl silicon rhodamine (QA-2MeSiR), showed 96.3% sensitivity and 85.2% specificity for visualization of lung cancer in surgically resected specimens within 10 min. In order to further reduce the background fluorescence while retaining the same side-chain structure, we modified QA-2MeSiR to obtain glutamine-alanine-2-methoxy silicon rhodamine (QA-2OMeSiR). This probe rapidly visualized even borderline lesions. Dipeptidyl peptidase 4 and puromycin-sensitive aminopeptidase were identified as enzymes mediating the cleavage and consequent fluorescence activation of QA-2OMeSiR, and it was confirmed that both enzymes are expressed in lung cancer. QA-2OMeSiR is a promising candidate for clinical application.

Effect of intraoperative needle biopsy on the survival of nonsmall cell lung cancer patients: a propensity score matching analysis.

PURPOSE: It is unknown whether intraoperative needle biopsy (INB) predisposes to the postoperative recurrence of lung cancer and compromises the prognosis of these patients. We conducted this study to identify the effect of INB before lobectomy on the postoperative recurrence rate and prognosis of patients with nonsmall cell lung cancer (NSCLC). METHODS: The subjects of this retrospective study were 953 patients with pathological stage I-III NSCLC who underwent lobectomy between 2001 and 2016. The patients were divided into two groups: the INB group (n = 94) and the non-INB group (n = 859). After propensity score matching (PSM), we compared the postoperative cumulative recurrence rate, recurrence-free survival (RFS), disease-specific survival (DSS), and overall survival (OS) between the two groups. RESULTS: After PSM, 94 patient pairs were matched. The cumulative recurrence rate was significantly higher in the INB group than in the non-INB group (P = 0.01). The 5-year RFS rate was significantly lower in the INB group than in non-INB group (48% vs 68%), as were the 5-year DSS (76% vs 92%) and 5-year OS rates (67% vs 84%) (all P < 0.05). CONCLUSIONS: The findings of this analysis suggest that INB before lobectomy may increase the cumulative recurrence rate and worsen the prognosis of patients with resectable NSCLC. Thus, we believe that INB should be avoided unless a lung lesion cannot be diagnosed by another type of biopsy.

Preoperative lung surface localization for pulmonary wedge resection: a single-center experience.

BACKGROUND: Preoperative lung surface localization is effective in sublobar resection for small lung nodules. However, the efficacy may vary depending on the underlying conditions of the lung and tumor, as well as the technique. This study aimed to evaluate the efficacy and limitations of preoperative lung surface localization for wedge resection by analyzing the outcomes of computed tomography (CT)-guided percutaneous marking and virtual-assisted lung mapping (VAL-MAP). METHODS: We investigated 215 patients who underwent curative wedge resection for malignant tumors using CT-guided localization or VAL-MAP from 1998 to 2018 in our institute. Each resected nodule was assessed for successful resection, which was defined as complete resection with adequate margins. RESULTS: One-hundred-and-nineteen patients with 153 nodules were included. The overall successful resection rate was 87.6%. The successful resection rate was significantly lower for nodules with intraoperative adhesion than those without intraoperative adhesion (75.0% vs. 90.1%; P=0.034), and for tumors requiring deep resection margins (>31 mm) than those requiring shallow margins (≤31 mm) (76.7% vs. 94.6%; P=0.002). Although the successful resection rate for nodules resected using CT-guided localization was significantly lower in cases with versus without intraoperative adhesion (54.5% vs. 86.7%; P=0.048), the successful resection rate for nodules resected using VAL-MAP was not influenced by the presence or absence of adhesion (85.7% vs. 93.4%; P=0.491). CONCLUSIONS: A requirement for deeper resection and the presence of intraoperative adhesion were limitations of preoperative lung surface localization for curative pulmonary wedge resection.

ɤ-glutamyl hydroxymethyl rhodamine green fluorescence as a prognostic indicator for lung cancer.

OBJECTIVE: ɤ-glutamyltranspeptidase is an enzyme expressed in various malignancies including lung cancer. It rapidly activates non-fluorescent ɤ-glutamyl hydroxymethyl rhodamine green to highly fluorescent hydroxymethyl rhodamine green. The resultant tumor fluorescence is therefore an indicator of cellular ɤ-glutamyltranspeptidase activity. We have explored the use of ɤ-glutamyl hydroxymethyl rhodamine green as an intraoperative imaging tool for visualizing cancers. Herein, we evaluated the potential of the tumor fluorescence as a postoperative prognostic indicator. METHODS: We included patients with non-small cell lung cancer who had undergone radical resection from 2012 to 2014 in the study. We assessed the fluorescence intensity of the resected tumor and normal lung tissue by ex vivo imaging using ɤ-glutamyl hydroxymethyl rhodamine green. RESULTS: Sixty-seven patients were eligible for the study (adenocarcinomas, n = 44; squamous cell carcinoma, n = 14; other histologies, n = 8). The pathological stages were I, II, III, and IV in 39, 15, 12, and 1 patient, respectively. Based on the fluorescence of the tumor tissue, the patients were divided into high fluorescence (n = 33) and low fluorescence (n = 34) groups. The 5-year overall survival rate was significantly higher in the high fluorescence group (72.7%) compared to the low fluorescence group (47.1%, P = 0.025). Similarly, pathological stage I patients of the high fluorescence group had higher 5-year overall survival (85.7% vs. 44.4%, P = 0.009) and recurrence-free survival (76.2% vs. 44.4% P = 0.044) rates compared to those of the low fluorescence group. CONCLUSIONS: ɤ-glutamyl hydroxymethyl rhodamine green fluorescence is a good postoperative prognostic indicator in patients with non-small cell lung cancer.

Flat Chest of Pleuroparenchymal Fibroelastosis Reversed by Lung Transplantation.

A patient with pleuroparenchymal fibroelastosis (PPFE) was successfully treated with living-donor lobar lung transplantation. A 27-year-old woman with a 3-month history of dyspnea received a diagnosis of PPFE. Her chest wall was extremely flattened over time, and her respiratory condition progressively deteriorated. She underwent semielective bilateral living-donor lobar lung transplantation. Her chest wall rigidity, which was secondary to PPFE, required intensive pulmonary rehabilitation postoperatively. By 6 months after transplantation, the flattening of her chest wall was reversed. Living-donor lobar lung transplantation was a life-saving procedure for this patient and improved the chest wall deformity of PPFE.

Phrenic nerve reconstruction in complete video-assisted thoracic surgery.

OBJECTIVES: Primary or metastatic lung cancer or mediastinal tumours may at times involve the phrenic nerve and pericardium. To remove the pathology en bloc, the phrenic nerve must be resected. This results in phrenic nerve paralysis, which in turn reduces pulmonary function and quality of life. As a curative measure of this paralysis and thus a preventive measure against decreased pulmonary function and quality of life, we have performed immediate phrenic nerve reconstruction under complete video-assisted thoracic surgery, and with minimal additional stress to the patient. This study sought to ascertain the utility of this procedure from an evaluation of the cases experienced to date. METHODS: We performed 6 cases of complete video-assisted thoracic surgery phrenic nerve reconstruction from October 2009 to December 2013 in patients who had undergone phrenic nerve resection or separation to remove tumours en bloc. In all cases, it was difficult to separate the phrenic nerve from the tumour. Reconstruction involved direct anastomosis in 3 cases and intercostal nerve interposition anastomosis in the remaining 3 cases. RESULTS: In the 6 patients (3 men, 3 women; mean age 50.8 years), we performed two right-sided and four left-sided procedures. The mean anastomosis time was 5.3 min for direct anastomosis and 35.3 min for intercostal nerve interposition anastomosis. Postoperative phrenic nerve function was measured on chest X-ray during inspiration and expiration. Direct anastomosis was effective in 2 of the 3 patients, and intercostal nerve interposition anastomosis was effective in all 3 patients. Diaphragm function was confirmed on X-ray to be improved in these 5 patients. CONCLUSIONS: Complete video-assisted thoracic surgery phrenic nerve reconstruction was effective for direct anastomosis as well as for intercostal nerve interposition anastomosis in a small sample of selected patients. The procedure shows promise for phrenic nerve reconstruction and further data should be accumulated over time.