Effect of revised organ transplant law in Japan on lung transplantation.

PURPOSE: To investigate how revision of the organ transplant law in Japan affected lung transplantation in this country. METHODS: Lung transplant candidates registered between January, 2000 and December, 2009 were designated as the pre-revision group (n = 396) and those registered between January, 2011 and December, 2020, as the post-revision group (n = 1326). Both groups were analyzed retrospectively using data collected by the Japanese Society of Lung and Heart-Lung Transplantation. RESULTS: The number of patients who underwent brain-dead donor lung transplantation (BDLT) increased significantly after the law amendment (32.2 vs. 13.8%, p < 0.01). The median waiting time for BDLT was significantly reduced (708 days vs. 1163 days, p < 0.01) and the mortality rate while waiting for BDLT improved significantly after the law amendment (33.1 vs. 42.6%, p < 0.01). In the post-revision group, 18 pediatric patients underwent BDLT. The 5-year survival rates after BDLT were comparable between the groups (73.5% in the pre-revision group vs. 73.2% in the post-revision group, p = 0.32). CONCLUSIONS: The organ transplant law revision shortened the waiting time for BDLT significantly and decreased the mortality rate while waiting for BDLT. The posttransplant outcomes in Japan remained favorable throughout the study period.

Donor management and extremely high donor lung utilization rate in Japan.

Owing to the extremely short supply of donor lungs in Japan, a unique medical consultant (MC) system was initiated in 2002 to increase the organ availability through intensive management of donors. First, heart transplant surgeons were sent to procurement hospitals as MCs to assess donor organ function and provide intensive care to donors. MCs requested that donor attending doctors perform frequent phlegm aspiration with a bronchoscope, leading to a higher lung availability and better outcomes after lung transplantation. Since 2011, 25 lung transplant surgeons have been registered as lung MCs to assess and manage donor lungs and communicate donor lung conditions to the lung transplantation teams. In 2014, the efficacy of this MC system on lung transplantation opportunities and outcomes was retrospectively reviewed. One hundred and eighty-seven brain-dead lung donor candidates were chronologically divided into three phases: I (May 1998 to November 2006, n=44) and II (December 2006 to January 2011, n=64), before and after MCs requested that local attending doctors perform aggressive bronchial suctioning using a bronchoscope, respectively; and III (February 2011 to January 2013, n=79), after the emergence of lung MCs. The lung utilization rates in phases I, II, and III were 61.4%, 71.9%, and 74.7% (per donor); 51.1%, 64.8%, and 67.7% (per lung, P=0.03). Graft death rates due to primary graft dysfunction in phases I, II, and III were 13.3%, 3.6%, and 3.7%, respectively (per lung, P=0.04). Recently, we analyzed the utilization rate of 63 brain-dead lung donor candidates for a period of one year, from June 2020 to May 2021, which was 83% (per donor). The lung MC system is effective in maintaining an extremely high lung utilization rate and favorable outcomes after lung transplantation in Japan.

Effects of case volume on short- and long-term outcomes following cadaveric lung transplantation in Japan.

Background: Despite the low number of lung transplantations (LTs) in Japan, 10 LT facilities are accredited and good outcomes have been reported. A database review was conducted to clarify the impact of case volume at LT facilities in Japan on short- and long-term outcomes. Methods: All cadaveric LT cases treated between 2000 and 2021 in Japan were analyzed using the database of the Japanese Society of Lung and Heart-Lung Transplantation (JSLHT). The nine institutions represented were categorized into the low-volume (LV; <80 cumulative LT cases, <8 LTs/year, n=5) and high-volume (HV; ≥80 cumulative LT cases, ≥8 LTs/year, n=4) centers. Ninety-day and 1-year mortality, as well as 5- and 10-year survival data were evaluated. Results: A total of 658 cadaveric LTs were performed at the nine institutions. The 90-day rates of mortality at the HV and LV centers were 3.5% and 3.9%, respectively (P=0.801), while the 1-year mortality rates were 9.2% and 11.5%, respectively (P=0.199). Additionally, log-rank analysis of Kaplan-Meier curves showing case volume did not reveal a significant difference in long-term survival between the HV and LV centers (P=0.272), though the LV centers had wide differences for long-term outcomes (P=0.030). Conclusions: Case volume did not have effects on short- or long-term outcomes following LT in Japan, while there were large variations in long-term outcomes among the LV centers compared to those of the HV centers.

The consecutive impact of COVID-19 on thoracic surgical procedures in Japan: an analysis of data from the National Clinical Database.

PURPOSE: The current study was designed to analyze the impact of the COVID-19 pandemic on general thoracic surgeries in Japan. METHODS: Changes in surgeries for lung cancer and metastatic lung tumors were evaluated based on National Clinical Database data regarding cancer screening. RESULTS: In 2021, surgeries for primary lung cancer increased by 3.4% compared to 2020, which, given the increase from 2014 to 2019, indicates an overall 11.1% decrease. In contrast, surgeries for metastatic lung tumors in 2021 decreased by 5.8% compared to 2020, which, given the increase from 2014 to 2020, indicates an overall 9.2% decrease. Half of the primary diseases for metastatic lung tumor were cases of colorectal cancer. Low anterior resection procedures in 2020 decreased by 5.5% compared to 2019. Lung and colon cancer screening examinees in 2021 were increased compared to 2020; however, they still showed respective decreases of 11% and 9.0% compared to 2019. CONCLUSIONS: Surgeries for primary lung cancer still decreased substantially during the COVID-19 pandemic. The continued stagnation of screening was responsible for this decrease. Surgeries for metastatic lung tumors decreased profoundly, and the decrease in screening for primary tumors was responsible for this reduction. Our findings emphasize the significance of maintaining cancer screening efforts, even during a pandemic.

Prognostic factors for lung transplant recipients focusing on age and gender: the Japanese lung transplantation report 2022.

PURPOSE: To clarify the impact of donor and recipient characteristics on the survival of recipients before and after lung transplantation in the Japanese population. METHODS: Patients' data were collected for retrospective analysis from all authorized lung transplant centers in Japan. We included 1963 patients listed for lung transplantation by the end of December 2021, comprised of 658 deceased-donor and 270 living-donor lung transplants. RESULTS: Primary disease had a significant impact on the mortality of patients waiting for transplantation. The indications for transplant significantly affected the post-transplant survival rate of deceased-donor lung transplant recipients. The recipient's age also significantly affected the post-transplant survival rate of the deceased-donor and living-donor lung transplant recipients. The recipients of grafts transplanted from donors aged 61 years or older showed a worse post-transplant survival rate (≧60 years old). The survival rate for the combination of a female donor to a male recipient among the deceased-donor lung transplant recipients was the worst among the four combinations. CONCLUSION: The donor and recipient characteristics significantly impacted the survival of recipients after lung transplantation. The underlying mechanism of the negative impact of the gender mismatch of female donor to male recipient on post-transplant survival needs to be investigated further.

Honeycomb lung is a major risk factor for preoperative radiological tumor size underestimation in patients with primary lung cancer.

Background: Lung cancer frequently occurs in lungs with background idiopathic interstitial pneumonias (IIPs). Limited resection is often selected to treat lung cancer in patients with IIPs in whom respiratory function is already compromised. However, accurate surgical margins are essential for curative resection; underestimating these margins is a risk for residual lung cancer after surgery. We aimed to investigate the findings of lung fields adjacent to cancer segments affect the estimation of tumor size on computed tomography compared with the pathological specimen. Methods: This analytical observational study retrospectively investigated 896 patients with lung cancer operated on at Fujita Health University from January 2015 to June 2020. The definition of underestimation was a ≥10 mm difference between the radiological and pathological maximum sizes of the tumor. Results: The lung tumors were in 15 honeycomb, 30 reticulated, 207 emphysematous, and 628 normal lungs. The ratio of underestimation in honeycomb lungs was 33.3% compared to 7.4% without honeycombing (P=0.004). Multivariate analysis showed that honeycombing was a significant risk factor for tumor size underestimation. A Bland-Altman plot represented wide 95% limits of agreement, -40.8 to 70.2 mm, between the pathological and radiological maximum tumor sizes in honeycomb lungs.

The phase angle as a predictor of postoperative complications in patients undergoing lung cancer surgery.

PURPOSE: The phase angle (PhA), calculated by bioelectrical impedance analysis, is used as a nutritional risk indicator. A low preoperative PhA has been reported as a marker of postoperative complications in patients with cancer; however, the relationship between the PhA and postoperative complications in patients with lung cancer remains unknown. We conducted this study to assess the predictive ability of the preoperative PhA for postoperative complications in patients undergoing surgery for primary lung cancer. METHODS: We reviewed the data on 240 patients who underwent surgery for primary lung cancer at our institution between August, 2019 and August, 2021. RESULTS: The PhA value in this study was 4.7 ± 0.7°. According to the Clavien-Dindo classification, grade ≥ II postoperative complications occurred in 53 patients (22.0%). Based on the multivariate logistic analysis, only the PhA (odds ratio, 0.51, 95% confidence interval, 0.29-0.90, p = 0.018) was an independent predictor of Clavien-Dindo grade ≥ II postoperative complications. CONCLUSIONS: The PhA may be a valuable marker for predicting the risk of postoperative complications following lung cancer surgery.

Living Donor Lobar Lung Transplant for a Patient With Lung Disease Caused by ABCA3 Gene Mutations: A Case Report.

Recessive gene mutations in ABCA3 cause lethal neonatal respiratory distress, and pediatric and adult interstitial lung disease. The effectiveness of medical treatments is limited and a subset of such patients will eventually require lung transplantation. A 20 months old boy developed interstitial lung disease and was treated with hydroxychloroquine, which had a significant effect. Sequence analysis of ABCA3 gene revealed newly discovered compound heterozygous mutations. His respiratory dysfunction gradually progressed over years and he underwent living-donor lobar lung transplantation (LDLLT) at 8 years of age with his parents serving as bilateral lobar donors. The parents had been genetically examined beforehand and found to be carriers who had one allele with an ABCA3 gene mutation and the other with no mutation. The recipient has been well without chronic lung allograft dysfunction and his parents have been enjoying healthy social lives for 7 years since the operations. LDLLT appears to be a valid option for selected children with ABCA3 gene mutations who are too ill to wait for cadaveric lung transplantation. When relatives of the recipient with ABCA3 gene mutation are deemed potential donors for LDLLT, sequence analyses of the donors are indispensable to exclude the possibility that they are late-onset patients of this recessive hereditary disease.

The impact of COVID-19 on thoracic surgical procedures in Japan: Analysis of data from the National Clinical Database.

OBJECTIVE: The COVID-19 pandemic has far-reaching collateral health impacts on the ongoing delivery of surgical care worldwide. The current study was designed to analyze the impact of the COVID-19 pandemic on the number of surgeries of general thoracic surgery in Japan. METHODS: Changes in the number of surgeries for total and three representative tumors were analyzed using the National Clinical Database data with reference to the pandemic infection rate and lung cancer screening. RESULTS: In 2020, the number of surgeries in total and for primary lung cancer and mediastinal lung tumor decreased by 4.9, 5.1, and 5.0 %, respectively. Considering the five-year trend towards a 5 % annual increase, there was a potential 10 % decrease in the number of primary lung cancer surgeries. The number of primary lung cancer surgeries bottomed in July 2020 but recovered towards the end of the year. In contrast, the number of metastatic lung tumor surgeries in 2020 increased by 3.2 %, following a similar trend observed over the previous five years. The number of lung cancer screening examinees decreased markedly with the lowest number in May. Our findings indicate that surgical triage had a limited impact on the decrease in primary lung cancer surgeries during the pandemic; rather, the decrease in lung cancer screening, which was a few months preceding, is most likely responsible. CONCLUSIONS: The decrease in primary lung cancer was mainly caused by the decrease in lung cancer screening, indicating that continuing screening is vital even during a pandemic.

[Traumatic Diaphragmatic Injury].

Traumatic diaphragmatic injury( TDI) is rare in traumas, however TDI is associated with high mortality. We follow the notation method by The Japanese Association for The Surgery of Trauma. There are blunt trauma and penetrating trauma of TDI;blunt trauma causes mainly traffic accidents, and penetrating trauma is induced stub or gunshot. Penetrating trauma is more frequent than blunt trauma in Western countries, however there are mainly blunt traumas in Japan. The timing of diagnosis are three points;acute phase, subacute phase and delayed phase. In acute phase we often experienced unstable vital sign, so the patients of TDI need treatment immediately, however in delayed phase the patients of TDI are stable in vital signs. In order to diagnose for TDI, we use chest X-ray and computed tomography (CT), which is useful to diagnose by multi-planar reconstruction of multi-detector row CT. The ways to approach to TDI are from thoracotomy, laparotomy or both. When we repair the diaphragmatic injury, usually interrupted or horizontal mattress suture was applied with non-absorbable string. The mortality is about 8.8 to 19.8% by TDI, so we need to carefully diagnose TDI as soon as possible whether complication and abdominal viscera injury exist or not.

γH2AX, a DNA Double-Strand Break Marker, Correlates with PD-L1 Expression in Smoking-Related Lung Adenocarcinoma.

In recent years, the choice of immune checkpoint inhibitors (ICIs) as a treatment based on high expression of programmed death-ligand 1 (PD-L1) in lung cancers has been increasing in prevalence. The high expression of PD-L1 could be a predictor of ICI efficacy as well as high tumor mutation burden (TMB), which is determined using next-generation sequencing (NGS). However, a great deal of effort is required to perform NGS to determine TMB. The present study focused on γH2AX, a double-strand DNA break marker, and the suspected positive relation between TMB and γH2AX was investigated. We assessed the possibility of γH2AX being an alternative marker of TMB or PD-L1. One hundred formalin-fixed, paraffin-embedded specimens of lung cancer were examined. All of the patients in the study received thoracic surgery, having been diagnosed with lung adenocarcinoma or squamous cell carcinoma. The expressions of γH2AX and PD-L1 (clone: SP142) were evaluated immunohistochemically. Other immunohistochemical indicators, p53 and Ki-67, were also used to estimate the relationships of γH2AX. Positive relationships between γH2AX and PD-L1 were proven, especially in lung adenocarcinoma. Tobacco consumption was associated with higher expression of γH2AX, PD-L1, Ki-67, and p53. In conclusion, the immunoexpression of γH2AX could be a predictor for the adaptation of ICIs as well of as PD-L1 and TMB.

[Current Status and Tasks of the Lung Medical Consultant System].

In order to overcome challenges of serious short supply of donor organs, a unique partnership between transplant consultant doctors and local physicians, named medical consultant( MC) system, started in 2002 to maximize the organ utilization rate. As the first step of this system, skillfull heart transplant surgeons were sent to procurement hospitals as MCs to assess donor organ function and provide intensive care to donors. Since 2006, the MC doctors have requested the donors' attending physicians to perform aggressive bronchial suctioning using bronchoscopy, leading to an improved lung utilization rate and better graft survival. Since 2011, more than 25 lung MCs have been registered to assess donor lungs and provide advices on intensive respiratory care to donors. The effects of this system on lung transplantation opportunities and outcomes were retrospectively reviewed in 187 brain-dead lung donor candidates, which were chronologically divided into 3 phases:Ⅰ( May 1998 to November 2006, n=44) and Ⅱ( December 2006 to January 2011, n=64), before and after MCs requested local attending physicians to perform aggressive bronchial suctioning using bronchoscopy, respectively;and phase Ⅲ (February 2011 to January 2013, n=79), after the emergence of lung MCs( Hoshikawa Y, et al. Transplant Proc 47( 3):746-750, 2015). The lung utilization rates in phases Ⅰ, Ⅱ, and Ⅲ, were 61, 72, and 75%( per donor);51, 65, and 68% (per lung, p=0.03). Graft death due to primary graft dysfunction was significantly more frequent in phase Ⅰ (13.3%) than in phases Ⅱ (3.6%) and Ⅲ (3.7%, per lung, p=0.04). The lung utilization rate of 63 brain-dead lung donor candidates for a period of one year from June 2020 to May 2021, which was analyzed anew for this article, was 83%( per donor) and 72%( per lung). We discussed current status and tasks of the lung MC system which has been operated for 10 years.

Tracheobronchial reconstruction by inverted Barclay's method for tracheobronchial injury in an 8-year-old girl: a case report.

BACKGROUND: Tracheobronchial injury in children is rare but can be highly fatal in severe cases. Therefore, prompt diagnosis and treatment are required. The appropriate treatment method depends on the extent and severity of the injury. CASE PRESENTATION: An 8-year-old girl fell from the fifth floor and was transported to a local hospital. She had a tracheobronchial injury, went into cardiopulmonary arrest during transportation to our hospital. She was revived with cardiopulmonary resuscitation, and veno-arterial extracorporeal membrane oxygenation (VA-ECMO) was commenced. Subsequently, we performed tracheobronchial reconstruction by inverted Barclay's method for tracheobronchial injury. She was switched from VA-ECMO to venovenous (VV)-ECMO 4 days postoperatively, and VV-ECMO was eventually discontinued 27 days after the surgery. The patient was awake and weaned off the ventilator on postoperative day 58. She was discharged 97 days after the surgery. CONCLUSIONS: Tracheobronchial reconstruction by inverted Barclay's method is the preferred surgical technique when other reconstruction techniques are expected to cause excessive tension on the anastomosis of the right main bronchus.

Aortogenic embolic stroke after sleeve pneumonectomy with median sternotomy for lung cancer: a case report.

BACKGROUND: The median sternotomy approach in sleeve pneumonectomy enables diseased lung ventilation in selected cases, which may reduce the difficulty in achieving anastomosis under intubation of the left main bronchus. However, with median sternotomy, the ascending aorta requires repeated mobilization to expose the operative field for anastomosis, which can cause an aortogenic embolic stroke. CASE PRESENTATION: A 70-year-old Asian man presenting 6 months after developing hemoptysis was diagnosed with right upper lobe lung cancer (stage T4N0M0), invading the lower trachea and basal bronchus. Preoperative computed tomography revealed ascending aorta calcification. Right sleeve pneumonectomy was performed using median sternotomy with diseased lung ventilation. The ascending aorta was repeatedly mobilized to adequately expose the tracheobronchial bifurcation. Surgery was uneventful, but he did not recover complete consciousness even after termination of anesthesia. Mild paralysis of both upper extremities was observed. Head magnetic resonance imaging on postoperative day 1 revealed multiple small acute infarctions in the brain, possibly caused by mobilization of the aorta. He received anticoagulation therapy and rehabilitation and was discharged on postoperative day 30. CONCLUSION: The median sternotomy approach in sleeve pneumonectomy enables diseased lung ventilation. However, the possibility of aortogenic embolic stroke should be considered when calcification of the ascending aorta is observed on preoperative computed tomography.

Evaluation of prognosis after thoracoscopic lobectomy for primary lung cancer.

INTRODUCTION: Thoracoscopic lobectomy for primary lung cancer is performed at many institutions. However, few reports are available on postoperative prognosis for progressive stages. In 2004, we adopted lobectomy by video-assisted thoracoscopic surgery (VATS), which would be applicable to the clinical stages up to stage IIIA. This study reports long-term outcomes of surgery for primary lung cancer at several stages, including IIIA. METHODS: We compared the long-term outcomes of 315 VATS cases with those of 159 open thoracotomy cases. RESULTS: The overall 5-year survival rate was 78.1% for the VATS group and 61.9% for the open thoracotomy group. A statistically significant difference between the survival curves of the two groups was observed (P = .001). When analyzing the survival curves for both groups by pathological (p) stage, significant differences were observed for p-stages IB and IIIA, with the VATS group producing better results than the open thoracotomy group. CONCLUSION: The long-term outcomes of patients with primary lung cancer at our institution were more favorable in the group undergoing VATS lobectomy than in the group undergoing open thoracotomy.

Subxiphoid uniportal bilateral lung wedge resection.

Subxiphoid uniportal bilateral lung wedge resection, in which all manipulations are performed via a 3-cm wound positioned below the xiphoid process, can be performed in the supine position without the patient having to change positions. It also enables one-stage bilateral lung resection. We report the surgical procedure and initial results of subxiphoid uniportal bilateral lung wedge resection. A 3-cm transverse incision was made 1 cm caudally below the xiphoid process. A port for uniportal surgery was inserted. After CO2 insufflation at 8 mmHg, the lung was grasped and lifted with bent grasping forceps, and by bending the tip of a stapler, the surgeon resected the affected portion of the bilateral lungs. In this approach, there is one incision, no intercostal nerve damage and bilateral surgery can be performed in the same procedure; therefore, the technique may have the benefit of lesser invasiveness for the patient. Furthermore, a detailed comparison of subxiphoid uniportal bilateral lung wedge resection with the one-stage lateral intercostal approach with a larger subject sample is needed.

Early outcomes in 147 consecutive cases of subxiphoid single-port thymectomy and evaluation of learning curves.

OBJECTIVES: The aim of the present study was to examine some initial results and learning curves concerning subxiphoid single-port thymectomy (SSPT), thereby clarifying the safety of this surgical approach and describing the precautions for adopting it. METHODS: From March 2011 to August 2019, a total of 203 patients underwent thymectomy for either anterior mediastinal tumours or myasthenia gravis at Fujita Health University Hospital. Of these 203 patients, 147 patients who had undergone SSPT were selected as participants for the present study. RESULTS: Of the 147 cases, transition to a different approach was required in three (2.0%) cases: two (1.3%) cases transitioned to median sternotomy, whereas one (0.7%) case transitioned to the side chest trans-intercostal approach. The two cases that transitioned to median sternotomy were the second cases for different operators after they began performing this technique. There were six (4.0%) cases with complications and no deaths. The operation time cumulative summation learning curve analysis revealed that the curves descended from the 38th case. In the 83 cases handled by one surgeon, the learning curves descended from the 31st case. CONCLUSIONS: SSPT is a safe modality with few complications and no associated cases of mortality reported. Operators are required to experience 31-38 cases until the operation time for SSPT was stabilized. Special care should be exercised to prevent vascular damage in the vicinity of the innominate veins during the early stages after SSPT introduction.

Ex vivo lung CT findings may predict the outcome of the early phase after lung transplantation.

PURPOSE: We developed an ex vivo lung CT (EVL-CT) technique that allows us to obtain detailed CT images and morphologically assess the retrieved lung from a donor for transplantation. After we recovered the lung graft from a brain-dead donor, we transported it to our hospital and CT images were obtained ex vivo before lung transplant surgery. The objective of this study was to investigate the correlation between the EVL-CT findings and post-transplant outcome in patients who underwent bilateral lung transplantation (BLT) or single lung transplantation (SLT). METHODS: We retrospectively reviewed the records of 70 patients with available EVL-CT data who underwent BLT (34 cases) or SLT (36 cases) in our hospital between October 2007 and September 2017. The recipients were divided into 2 groups (control group, infiltration group) according to the findings of EVL-CT of the lung graft in BLT and SLT, respectively. Recipients in the control group were transplanted lung grafts without any infiltrates (BLT control group, SLT control group). Recipients in the infiltration group received lung grafts with infiltrates (BLT infiltration group, SLT infiltration group). RESULTS: The recipients in the BLT infiltration group showed significantly slower recovery from primary graft dysfunction and a longer mechanical ventilation period and ICU stay period than those in the BLT control group. The mechanical ventilation period was significantly longer in the recipients in the SLT infiltration group than those in the SLT control group. CONCLUSION: EVL-CT may predict the outcome of the early phase after lung transplantation.

Uniportal video-assisted thoracic surgery lowers the incidence of post-thoracotomy pain syndrome.

OBJECTIVE: We compared post-thoracotomy pain syndrome (PTPS) incidence in patients who underwent uniportal or multiportal video-assisted thoracoscopic surgery (VATS). METHODS: We included 223 patients who underwent either uniportal or multiportal VATS between January 2017 and October 2018 (pulmonary lobectomies and pulmonary segmentectomies-uniportal: n=19, multiportal: n=133; wedge lung resections-uniportal: n=16, multiportal: n=55). We retrospectively studied incidences of PTPS in all subgroups. RESULTS: Incidences of PTPS were significantly less for uniportal procedures for both the pulmonary lobectomy/segmentectomy group (P=0.024) and the wedge lung resection group (P=0.0315) than for multiportal procedures. CONCLUSION: Patients who underwent uniportal VATS procedures had lower incidences of PTPS than the multiportal VATS group. The uniportal VATS approach is therefore beneficial for patients.