Robot-assisted thoracoscopic right upper lobectomy with displaced B3 and absence of minor fissure: a case report.

INTRODUCTION: B3 downward-shifting is a rare bronchial anomaly characterized by abnormal pulmonary arteries associated with downward displacement of B3 and complete fusion between the right upper and middle lobes. CASE PRESENTATION: We report a case of robot-assisted thoracoscopic right upper lobectomy in a patient with lung cancer with B3 downward-shifting. An 81-year-old male was diagnosed with non-small cell lung cancer in S3 of the right upper lung. Preoperative three-dimensional computed tomography angiography revealed a B3 bronchus derived from the middle lobe bronchus and an anterior segmental pulmonary artery variation. Robot-assisted thoracoscopic surgery right upper lobectomy with ND2a-1 was performed via four-port incisions and an assist incision. No interlobar fissure was observed between the right upper and middle lobes. After dissecting B1+2, the displaced B3 root was dissected. The displaced A3a was difficult to dissect because of an extremely severe complete fissure. Therefore, we dissected the bronchus preceding from the cranial side. To confirm a minor fissure, indocyanine green was administered intravenously, and the interlobar boundary was identified as the line separating the dark and green lung parenchyma. The boundary was divided using mechanical staples. No surgical complications occurred. CONCLUSIONS: Using three-dimensional reconstruction imaging and systemic indocyanine green administration, we successfully performed a right upper lobectomy through robot-assisted thoracic surgery.

Elderly lung transplant recipients show acceptable long-term outcomes for lung transplantation: A propensity score-matched analysis.

PURPOSE: Although the performance lung transplantation (LTx) in the elderly (≥ 60 years) has increased globally, the situation in Japan remains quite different, because the age limit at registration for cadaveric transplantation is 60 years. We investigated the long-term outcomes of LTx in the elderly in Japan. METHODS: This was a single-center retrospective study. We divided the patients into two groups according to age: the younger group (< 60 years; Y group; n = 194) and the elderly group (≥ 60 years; E group; n = 10). We performed three-to-one propensity score matching to compare the long-term survival between the E and Y groups. RESULTS: In the E group, the survival rate was significantly worse (p = 0.003), and single-LTx was more frequent (p = 0.036). There was a significant difference in the indications for LTx between the two groups (p < 0.001). The 5-year survival rate after single-LTx in the E group was significantly lower than that in the Y group (p = 0.006). After propensity score matching, the 5-year survival rates of the two groups were comparable (p = 0.55). However, the 5-year survival rate after single-LTx in the E group was significantly lower than that in the Y group (p = 0.007). CONCLUSION: Elderly patients showed acceptable long-term survival after LTx.

Donor's long-term quality of life following living-donor lobar lung transplantation.

INTRODUCTION: Living-donor lobar lung transplantation is an alternative procedure to deceased donation lung transplantation. It involves graft donation from healthy donors; however, only a few reports have discussed its long-term prognosis in living lung donors and their associated health-related quality of life. This study aimed to examine living lung donors' health-related quality of life. METHODS: In our cross-sectional survey of living lung donors, we assessed health-related quality of life-based on three key aspects (physical, mental, and social health) using the 36-Item Short Form Health Survey. We also evaluated chronic postoperative pain and postoperative breathlessness using the numeric rating scale and the modified Medical Research Council Dyspnea scale, respectively. RESULTS: We obtained consent from 117 of 174 living lung donors. The average scores of the living lung donors on the 36-Item Short Form Health Survey were higher than the national average. However, some donors had poorer physical, mental, and social health, with lower summary scores than the national averages. Low mental component summary predictors included donor age (<40 years; odds ratio = 10.2; p < .001) and recipient age (<18 years; odds ratio = 2.73; p < .032). Low role-social component summary predictors included high lung allocation score (≥50; odds ratio = 3.94, p < .002) and recipient death (odds ratio = 3.64; p = .005). There were no predictors for a physical component summary. Additionally, many donors did not complain of pain or dyspnea. CONCLUSIONS: Living lung donors maintained an acceptable long-term health-related quality of life after surgery. Potential donors should be informed of relevant risk factors, and high-risk donors should receive appropriate support.

The impact of prognostic nutrition index on the waitlist mortality of lung transplantation.

OBJECTIVE: The prognostic nutrition index (PNI), calculated using serum albumin and total lymphocyte count, is a recent topical index related to inflammation. Preoperative PNI is regarded as a new preoperative prognostic score in lung transplantation (LTx). This study aimed to investigate the impact of PNI at the time of registration as a prognostic parameter of mortality on the waiting list for LTx. METHODS: A retrospective review was conducted on the data of 132 adult patients registered for LTx in our department between January 2013 and June 2020. Patients who finally received LTx were analyzed as censored data. The overall survival was evaluated using the Kaplan-Meier method for pre-registered clinical factors including the PNI at the time of registration. Overall survival was calculated from the date of listing to the Japan Organ Transplant Network to the date of death. RESULTS: The low-PNI group had a significantly worse prognosis. Multivariate analysis demonstrated that age (p = 0.023), idiopathic interstitial pneumonia (p < 0.001), lung allocation score (LAS) (p < 0.001), and PNI (p < 0.001) were independent prognostic factors for waitlist mortality. CONCLUSIONS: PNI at the time of registration can be an independent prognostic parameter in registered candidates for LTx.

Lung recruitment after cardiac arrest during procurement of atelectatic donor lungs is a protective measure in lung transplantation.

Background: Brain-dead donors are susceptible to pulmonary atelectasis (AT). In procurement surgery, lung recruitment under circulatory conditions and cold-flushing for atelectatic donor lungs often provoke graft injury due to the acute blood inflow. We hypothesized that lung recruitment without blood circulation can mitigate graft injury. This study aimed to examine the benefits of lung recruitment subsequent to cardiac arrest using a porcine lung-transplant model. Methods: Thirteen donor pigs were categorized into the non-atelectatic (No-AT) group (n=3) representing a healthy control group; AT-BCR group (n=5), in which AT was reverted by conventional blood-circulated recruitment (BCR); and AT-no-BCR group (n=5), in which AT was reverted by no-BCR following circulatory arrest. In the atelectatic donor models, the left main bronchus was ligated for 24 hours prior to lung procurement. Left lung transplantation (LTx) was subsequently performed in the thirteen recipient pigs. After 6 hours evaluation, the recipients were euthanized and the lung grafts were excised. Results: The post-transplant PaO2/FiO2 ratio was significantly higher in the AT-no-BCR group than in the AT-BCR group (P=0.015). Wet/dry ratio, histological findings of graft injury and tissue interleukin-8 expression in the AT-no-BCR group were similar to those of the No-AT group. Conclusions: Lung recruitment without circulation after circulatory arrest could be more protective for atelectatic donor lung than the conventional procedure.

Inhibiting S100A8/A9 attenuates airway obstruction in a mouse model of heterotopic tracheal transplantation.

Although bronchiolitis obliterans syndrome (BOS) is a major cause of death after lung transplantation, an effective drug therapy for BOS has not yet developed. Here, we assessed the effectiveness of a neutralizing anti-S100 calcium binding protein (S100) A8/A9 antibody against BOS. A murine model of heterotopic tracheal transplantation was used. Mice were intraperitoneally administered control IgG or the S100A8/A9 antibody on day 0 and twice per week until they were sacrificed. Tissue sections were used to evaluate the obstruction ratio, epithelium-preservation ratio, α-smooth muscle actin (SMA)-positive myofibroblast infiltration, and luminal cell death. Quantitative reverse transcriptase-polymerase chain reaction analysis was performed to analyze the mRNA-expression levels of collagen, inflammatory cytokines, and chemokines on days 7, 14, and 21. The anti-S100A8/A9 antibody significantly improved the obstruction ratio and epithelium-preservation ratio, with less α-SMA-positive myofibroblast infiltration compared to the control group. Antibody treatment reduced the type-III collagen: type-I collagen gene-expression ratio. The antibody also significantly suppressed the number of dead cells in the graft lumen. The expression levels of tumor growth factor ß1 and C-C motif chemokine 2 on day 21, but not those of interleukin-1ß, interleukin-6, and tumor necrosis factor α, were significantly suppressed by S100A8/A9 antibody treatment. These findings suggest that S100A8/A9 may be a potential therapeutic target for BOS after lung transplantation.

One-step nucleic acid amplification for intraoperative diagnosis of lymph node metastasis in lung cancer patients: a single-center prospective study.

One-step nucleic acid amplification (OSNA) is a rapid intraoperative molecular detection technique for sentinel node assessment via the quantitative measurement of target cytokeratin 19 (CK19) mRNA to determine the presence of metastasis. It has been validated in breast cancer but its application in lung cancer has not been adequately investigated. 214 LNs from 105 patients with 100 primary lung cancers, 2 occult primary lung tumors, and 3 metastatic lung tumors, who underwent surgical lung resection with LN dissection between February 2018 and January 2020, were assessed. Resected LNs were divided into two parts: one was snap-frozen for OSNA and the other underwent rapidly frozen histological examination. Intraoperatively collected LNs were evaluated by OSNA using loop-mediated isothermal amplification and compared with intraoperative pathological diagnosis as a control. Among 214 LNs, 14 were detected as positive by OSNA, and 11 were positive by both OSNA and intraoperative pathological diagnosis. The sensitivity and specificity of OSNA was 84.6% and 98.5%, respectively. The results of 5 of 214 LNs were discordant, and the remainder all matched (11 positive and 198 negative) with a concordance rate of 97.7%. Although the analysis of public mRNA expression data from cBioPortal showed that CK19 expression varies greatly depending on the cancer type and histological subtype, the results of the five cases, except for primary lung cancer, were consistent. OSNA provides sufficient diagnostic accuracy and speed and can be applied to the intraoperative diagnosis of LN metastasis for non-small cell lung cancer.

Survival and prognostic factors in patients undergoing pulmonary metastasectomy for lung metastases from retroperitoneal sarcoma.

BACKGROUND: Soft-tissue sarcomas are rare malignancies that consist of many different histologic subtypes and arise in various locations in the body. In patients with lung metastases from retroperitoneal sarcomas, the long-term outcomes and prognostic factors are unknown. This study is a retrospective review of patients undergoing pulmonary metastasectomy for retroperitoneal sarcoma metastases at one institution, with the purpose of determining prognostic factors and clinical outcomes. METHODS: This is a single-center, retrospective cohort study of patients undergoing pulmonary metastasectomy for lung metastases from various sarcomas at Okayama University Hospital from January 2006 to December 2018. The Kaplan-Meier method and log-rank test were used for the analyses, and cut-off values of continuous variables were determined by a receiver operating characteristic curve analysis. RESULTS: Twenty-four patients underwent the first pulmonary metastasectomy for lung metastases from retroperitoneal sarcoma in our hospital. Leiomyosarcoma was the most common histologic subtype of retroperitoneal sarcoma (79.2%, n = 19). Median overall survival was 49.9 months, and the 3-year and 5-year survival rates after the first pulmonary metastasectomy were 62.5% and 26.4% respectively. In univariate analysis, age ≥56 years, disease-free interval < 15 months, and size of metastasis (≥ 27 mm) were associated with poor survival. CONCLUSION: Pulmonary metastasectomy can be considered as an effective management strategy in retroperitoneal sarcoma patients with lung metastases in appropriately selected cases, just as it is for other sarcomas.

Paediatric lung transplantation: the impact of age on the survival.

OBJECTIVES: We herein review the outcomes of paediatric lung transplantation (LTx) and analyse subgroups divided by age. METHODS: We retrospectively reviewed 43 consecutive paediatric LTx recipients (< 18 years old: cadaveric LTx [n = 9], living-donor lobar LTx [n = 34]). We also analysed subgroups of patients 1-6 years old (n = 10) and 7-17 years old (n = 33). RESULTS: The 1-, 5- and 10-year overall survival (OS) rates in paediatric recipients were 93%, 82% and 67%, respectively. The 1-, 5- and 10-year graft dysfunction (GD)-free survival rates in paediatric recipients were 85%, 59% and 31%, respectively. The 1- and 5-year OS in the 1- to 6-year-old vs. 7- to 17-year-old groups were 70% vs. 100% and 48% vs. 93%, respectively (p < 0.0001). The 1- and 5-year GD-free survival rates in the 1- to 6-year-old vs. 7- to 17-year-old groups were 60% vs. 93% and 24% vs. 69%, respectively (p = 0.024). The 1- to 6-year-old group showed higher rates of non-standard LTx (p = 0.0001), interstitial pneumonia (p = 0.004) and ventilator dependency (p = 0.007) than the 7- to 17-year-old group. CONCLUSION: Paediatric recipients under 7 years old seemed to have a higher risk of mortality and GD than those 7 years old and older.

Completely Video-assisted Thoracoscopic Lobectomy for Congenital Lobar Emphysema in a Young Adult.

Congenital lobar emphysema (CLE) is defined as the hyperinflation of pulmonary lobes due to obstruction of the flow of air via a known or unknown etiology, which causes pressure symptoms in the adjacent organs. CLE is mainly diagnosed in the neonatal period, and very few adult cases have been reported. Here we report a 34-year-old male with muscular dystrophy who was diagnosed with CLE on examination. He underwent a right lower lobectomy via 3-portal completely video-assisted thoracoscopic surgery, and his symptoms improved. Thoracoscopic surgery helped preserve the respiratory muscles and led to the improvement of respiratory function in this patient.

Acute Pulmonary Edema Due to Arteriovenous Shunt Placement After Lung Transplantation.

Lung transplant recipients often have complications of immunosuppressant-induced nephropathy, which may require renal replacement therapy. We report a case of unilateral lung edema and pulmonary hypertension due to arteriovenous fistula placement in a patient with unilateral chronic lung allograft dysfunction after bilateral living-donor lobar lung transplantation. Lung transplant recipients with limited residual vascular beds, such as lobar graft or severe deviation in lung perfusion, are vulnerable to the acute increase in blood flow due to arteriovenous fistula placement and pulmonary edema can easily develop regardless of the left ventricular function. Hence, careful volume control is required.

Role of surgery in a novel multimodal therapeutic approach to complete cure of advanced lung cancer: current and future perspectives.

Non-small cell lung cancer (NSCLC) is considered potentially curable by multimodal therapy in a subset of patients, including those with locally advanced (LA) disease or nodal spread, who would otherwise have a poor prognosis. Guidelines recommend perioperative chemotherapy with platinum-based regimens, with or without radiotherapy, as the standard treatment modality for high-risk resectable LA-NSCLC. Although the classical regimens of adjuvant chemotherapy have been platinum-based doublet or oral agents such as tegafur/uracil, some molecular targeted therapeutic agents and immune checkpoint inhibitors have been developed recently with an expected favorable effect. Recent trials of perioperative therapy using these agents have demonstrated favourable anticancer efficacy for LA-NSCLC with an acceptable adverse events profile. The ideal timing of perioperative therapy administration, before or after surgery, is still controversial. Because some speculation and concepts have arisen from basic research, several trials are ongoing to clarify the efficacy of newly developed agents in the adjuvant or neoadjuvant setting. This review discusses the role of surgery in the new era and analyzes when and which optimal perioperative multimodal therapy, including chemotherapy, radiotherapy, molecular-targeted therapy, and immunotherapy, should be administered for resectable or potentially resectable NSCLC to provide possible complete cure.

Lung Transplantation for Bronchiectasis Due to Hyperimmunoglobulin E Syndrome.

Hyperimmunoglobulin E syndrome (HIES) is one of the primary immunodeficiencies characterized by recurrent staphylococcal skin and lung infections that result in lung destruction and critically diminished pulmonary function. Despite the lack of definitive treatment, there have been no reports of successful lung transplantation for HIES patients. We report the case of a 42-year-old woman with HIES with progressive bronchiectasis whose pulmonary infection was controlled before transplantation, and subsequent lung transplantation was uneventful. Lung transplantation may be feasible in HIES if the patient is immunologically stable preoperatively and perioperative infections, especially Aspergillus infections, are well controlled.

Emphysematous changes and lower levels of plasma irisin are associated with bronchiolitis obliterans syndrome after bilateral living-donor lobar lung transplantation.

PURPOSE: Decreased irisin levels may be associated with the development of emphysema. Similarly, emphysematous changes may develop in patients with chronic lung allograft dysfunction (CLAD) after living-donor lobar lung transplantation (LDLLT). We investigated the severity of emphysematous changes and the relationship between irisin levels and CLAD after bilateral LDLLT and cadaveric lung transplantation (CLT). METHODS: The subjects of this retrospective study were 59 recipients of bilateral LDLLT (n = 31) or CLT (n = 28), divided into a non-CLAD group (n = 41), a LDLLT-CLAD group (n = 11), and a CLT-CLAD group (n = 7). We compared the severity of emphysematous changes, the skeletal muscle mass, and the plasma irisin levels among the groups. RESULTS: The emphysematous changes were significantly more severe in the LDLLT-CLAD and CLT-CLAD groups (p = 0.046 and 0.036), especially in patients with bronchiolitis obliterans syndrome (BOS), than in the non-CLAD group. Although the skeletal muscle mass was similar in all the groups, the plasma irisin levels were significantly lower in the LDLLT-CLAD group (p = 0.022), especially in the patients with BOS after LDLLT, than in the non-CLAD group. CONCLUSION: Emphysematous changes and lower levels of plasma irisin were associated with CLAD, especially in patients with BOS, after bilateral LDLLT.

Circulating anti-human leukocyte antigen IgM antibodies as a potential early predictor of allograft rejection and a negative clinical outcome after lung transplantation.

PURPOSE: Anti-human leukocyte antigen (HLA) immunoglobulin (Ig) M production stimulated by an alloantigen is sensitive, making IgM a novel potential marker of allorejection after organ transplantation. This study examined the relationship between the serum levels of anti-HLA IgM early after clinical lung transplantation (LTx) and the post-transplant outcomes. METHODS: Thirty-one consecutive patients who underwent deceased LTx were included. Immunoreactivity against HLA was retrospectively analyzed by measuring the anti-HLA IgM levels in the serum sampled for the first 14 days after LTx. The flow panel reactive antibody technique was used. The ratio of the anti-class I IgM level at each day to baseline was obtained, and the peak IgM level was determined for each case. The correlation between the peak IgM level and subsequent development of acute rejection (AR), chronic lung allograft dysfunction (CLAD), and survival outcomes were examined. RESULTS: The peak IgM level was a significant risk factor for AR within 90 days in univariate and multivariate analyses. In the long term, the patients with positive IgM (peak level > 1.8) tended to have a poorer CLAD-free and overall survival than those with negative IgM. CONCLUSION: Elevation of anti-HLA IgM levels early after LTx may be correlated with a higher incidence of rejection and negative clinical outcomes.

Long-term outcomes of living-donor lobar lung transplantation.

OBJECTIVE: Although living-donor lobar lung transplantation (LDLLT) enables an intermediate survival similar to cadaveric lung transplantation, the long-term outcome remains unknown. We examined the long-term outcomes of 30 patients who received LDLLT more than 16 years previously. METHODS: We retrospectively reviewed the clinical data of 30 patients who underwent LDLLT (bilateral LDLLT, 29 patients; single LDLLT, 1 pediatric patient) between October 1998 and April 2004. RESULTS: LDLLT was performed for 25 female and 5 male patients ranging in age from 8 to 55 years. The diagnoses included pulmonary hypertension (n = 11), pulmonary fibrosis (n = 7), bronchiolitis obliterans (n = 5), and others (n = 7). At a median follow-up of 205 months, 22 patients were alive and 8 were dead. The causes of death were infection (n = 3), malignancy (n = 2), acute rejection (n = 2), and chronic lung allograft dysfunction (CLAD; n = 1). Unilateral CLAD occurred in 17 patients (56.7%), but only 1 of these patients subsequently developed bilateral CLAD. Two patients underwent bilateral cadaveric lung retransplantations. The 5-, 10-, and 15-year CLAD-free survival rates were 80.0%, 62.8%, and 44.3%, respectively. Malignancy occurred in 7 patients. Two of 5 patients with chronic kidney disease requiring hemodialysis underwent living-donor kidney transplantation. The 5-, 10-, and 15-year overall survival rates were 96.7%, 86.7%, and 73.3%, respectively. CONCLUSIONS: Although only 2 lobes are implanted, LDLLT provides encouraging long-term outcomes. In patients with unilateral CLAD, the functioning contralateral graft might contribute to a favorable long-term outcome.

Effect of preoperative long-term use of corticosteroids on the development of post-transplant lymphoproliferative disorders after lung transplantation: a single-center experience in Japan.

PURPOSE: Post-transplant lymphoproliferative disorder (PTLD) is a major complication of lung transplantation (LTx). However, few studies on PTLD in Asian populations have been reported. We explored the characteristics of Japanese PTLD cases after LTx. METHODS: We retrospectively reviewed 195 cases of LTx at our institute. We summarized the clinical experiences of 7 PTLD cases and analyzed the patient characteristics and survival outcomes of patients with (n = 7) and without (n = 188) PTLD. RESULTS: All PTLD patients were taking corticosteroids preoperatively (p = 0.0030), and the duration of preoperative corticosteroid therapy was significantly longer in the PTLD group (p = 0.0064) than in the non-PTLD group. The overall survival after LTx was significantly worse in the PTLD group (p = 0.027) than in the non-PLTD group. Among the three patients who died within 1 year after the PTLD onset, two died of opportunistic infections without residual PTLD lesions. Chronic lung allograft dysfunction (CLAD) or bronchiolitis obliterans at an autopsy were diagnosed after PTLD treatment in four cases. CONCLUSIONS: Long-term preoperative corticosteroid therapy may be a risk factor for PTLD after LTx. Opportunistic infections are lethal complications of PTLD, regardless of the effectiveness of PTLD treatment. CLAD occurs at a high rate after PTLD treatment, and close monitoring is required.

Pulmonary Enteric Adenocarcinoma Harboring a BRAF G469V Mutation.

Pulmonary enteric adenocarcinoma (PEAC) is a rare subtype of lung cancer that should be differentiated from colorectal cancer metastasis. Little is known about its genetic background. An 84-year-old male with adenocarcinoma of the lung underwent left upper lobectomy. The histology of the surgical specimen was suggestive of PEAC. Gastrointestinal and colorectal fiberscopy revealed no evidence of colorectal cancer. Next-generation sequencing of the tumor identified a G469V substitution in serine/threonine-protein kinase B-raf (BRAF). Based on the higher prevalence of the G469 substitution in BRAF-mutant lung adenocarcinoma than in BRAFmutant colorectal cancer, the tumor likely originated from the lung. Identification of mutational genotype may be of some help in distinguishing PEAC from the lung metastasis of colorectal cancer.

[Redo Operation for Mediastinal Tumor].

The mediastinum contains large blood vessels, airways, and spinal cord, which are anatomically important parts of the human body because they survive by injury, obstruction, and compression, and are involved in activities of daily living( ADL). Therefore, even benign tumors have been indicated for aggressive surgical intervention. Dissection procedures from these anatomically important structures is extremely risky and difficult in reoperation for recurrence of mediastinal tumors, so careful consideration and attention must be paid to the surgical indications and methods. In this paper, we have described the points to be noted and points regarding the reoperation of mediastinal tumors with some review of the literature, including our own cases.