A randomized phase III trial of postoperative surveillance for pathological stage II and IIIA non-small cell lung cancer (JCOG2012, PHOENIX).

The goal of postoperative surveillance following non-small cell lung cancer surgery is to detect recurrence and second primary malignancies while curative treatment is still possible. Although several guidelines recommend that patients have computed tomography (CT) scans every 6 months for the first 2 years after resection, then once a year, there is no evidence that it is effective for survival, especially in locally advanced non-small cell lung cancer. In October 2022, we launched a multi-institutional, randomized controlled phase III trial for pathological stage II and IIIA non-small cell lung cancer patients to confirm the non-inferiority of less intensive surveillance with less frequent CT scans versus standard surveillance in terms of overall survival. The primary endpoint is overall survival. We intend to enroll 1100 patients from 45 institutions over 4 years. The trial has been registered in the Japan Registry of Clinical Trials under the code jRCT1030220361 (https://jrct.niph.go.jp/latest-detail/jRCT1030220361).

Salivary metabolites as potential predictive biomarkers for lung surgery complications: a retrospective cross-sectional study.

PURPOSE: Saliva is often used as a tool for identifying systemic diseases because of the noninvasive nature of its collection. Moreover, salivary metabolites can be potential predictive factors for postoperative survival. We conducted the present study to establish whether salivary metabolites can function as predictive biomarkers for lung surgery complications. METHODS: Unstimulated salivary samples were collected from 412 patients before lung surgery. Salivary metabolites were analyzed comprehensively by capillary electrophoresis mass spectrometry. Clinical data with the discriminatory ability of biomarkers were assessed to predict lung surgery complications using multivariate logistic regression analysis. The primary endpoint was the risk factors for postoperative complications of Clavien-Dindo grade ≥ III. RESULTS: Postoperative complications of Clavien-Dindo grade ≥ III developed in 36 patients (8.7%). There was no postoperative 30-day mortality. Male sex (odds ratio [OR], 3.852; 95% confidence interval CI 1.455-10.199; p = 0.007) and salivary gamma-butyrobetaine (OR, 0.809; 95% CI 0.694-0.943; p = 0.007) were identified as significant risk factors for postoperative complications of Clavien-Dindo grade ≥ III. CONCLUSION: Salivary metabolites are potential noninvasive biomarkers for predicting postoperative complications of lung surgery.

Development of a partnership between academia, community, and government in response to the 2022 mpox outbreak in Japan.

Objectives　In response to the steady rise in the number of cases of mpox in nonendemic countries, starting with an outbreak in the United Kingdom in May 2022, the World Health Organization declared a public health emergency of international concern on July 23, 2022. As of November 13, 2022, seven cases of mpox have been reported in Japan.Methods　A community engagement approach was applied to prevent the spread of mpox in Japan.Results　A tripartite partnership between academia, community, and government (ACG) was established to promote multisectoral communication between vulnerable communities, medical personnel involved in diagnosis and treatment, public health specialists at public health centers, epidemiologists at the National Institute of Infectious Diseases (NIID), and government and public administration. Through information sharing, this ACG partnership can translate accurate information into effective infection control measures.Conclusion　By developing and maintaining the ACG partnership, an environment will be created that allows an immediate response to future public health crises affecting vulnerable communities. This Practice Report describes the process of establishing an ACG partnership.

[Educational Impact of Using Three-dimentional Models for Preoperative Simulation of Segmentectomy for Medical Students].

BACKGROUND: Lung segment anatomy is complex and difficult for medical students to comprehend, so education is a challenging issue. Three-dimensional (3D) models may be a more effective teaching tool for medical students. We evaluated the usefulness of 3D models in education for segmentectomy. METHODS: Sixty-six students who participated in clinical training for thoracic surgery from November 2020 to March 2022 were included in the study. Computed tomography (CT) images, 3D-CT images, and 3D models were used to investigate students' level of understanding for each lung segment. Levels of understanding were assessed using a questionnaire administered using the interview method. The results of the questionnaire were tabulated and analyzed using the Kruskal-Wallis test. RESULTS: The response rate was 100%. Comprehension scores for all questions were highest for 3D models, followed by 3D-CT and CT. These results suggest that use of a 3D entity model may have a high educational effect. CONCLUSION: Although it is unclear whether students' comprehension was directly related to their understanding of correct anatomy, our results suggest that 3D models may be an effective way for medical students to understand lung segmentectomy.

Learning Curve for Thoracoscopic Individual Basilar Segmentectomy: 18-Year Experience.

BACKGROUND: Thoracoscopic anatomical individual basilar segmentectomy remains challenging owing to the deep intraparenchymal location of the hilar structures and anatomical variations. We analyzed and reported the experience and progress of thoracoscopic anatomical individual basilar segmentectomy at our university hospital. METHODS: We retrospectively examined the patients who underwent anatomical basilar segmentectomy at our institution from January 2004 to December 2021. We divided our analysis period into two parts: the first period (2004-2012) was the introductory period of video-assisted thoracoscopic surgery (VATS) segmentectomy, and the second period (2013-2021) was the maturity period of VATS segmentectomy. The learning curve of the leading surgeon in the second period was also evaluated based on the operative time and cumulative sum value of the operative time. RESULTS: Overall, 127 cases were evaluated, among whom 33 and 94 cases were assessed during the introductory and maturity periods of thoracoscopic segmentectomy, respectively. Age (P = 0.003) and Charlson comorbidity index (P = 0.002) were higher in the second period than in the first period. Use of a uniport (P = 0.006) was higher, and postoperative hospitalization duration (P = < 0.001) and operative time (P = 0.024) were shorter in the second period than in the first period. A learning curve obtained during the maturity period showed: The inflection point for the learning curve of thoracoscopic basilar segmentectomy was reached after 42 cases. CONCLUSIONS: We have demonstrated a single institution's progress and learning curve for difficult segmentectomies. This may be helpful to institutions considering performing this surgery.

[Minimally Invasive Surgery for Mediastinal Diseases in Our Institute:Innovations and Surgical Practice].

Since the early 1990s, minimally invasive surgery has been introduced in many surgical fields. The progress of technology and increased interest in minimally invasive surgery has led to innovation from surgery with a large incision to complete thoracoscopic surgery in many facilities. We started thoracoscopic mediastinal surgery in 1997 and robot-assisted mediastinal surgery in 2021. Considering the approach for anterior mediastinal tumor resection, it is necessary to fully understand tumor size, tumor location, and the existence of the tumor invasion to other organs. Especially in the case of tumors located on the cranial side above the innominate vein or thymectomy with dissection of the superior pole of the thymus, ensuring surgical field visibility is essential. In our institute, from the point of cosmetics, surgical field visibility is ensured using carbon dioxide insufflation and a sternum-lifting method. Although the number of cases is limited, we report our ingenuity and actual implementation of the techniques.

Time to Incurable Recurrence for Patients Treated With Pulmonary Metastasectomy for Colorectal Cancer.

BACKGROUND: Probability of cure is important for patients with lung metastasis who must decide whether to undergo metastasectomy. Although progression-free survival (PFS) is thought to reflect this, it does not include curative effects by repeat metastasectomy. Thus, the authors developed a new indicator, time to incurable recurrence (TTIR), in which only incurable recurrence was set as an event that included death, with incurable recurrence defined as recurrence not treated by definitive local therapy (DLT), recurrence treated by DLT but with PFS maintained less than 2 years, or recurrence followed by re-recurrence. METHODS: This multi-institutional study included 339 patients who underwent lung metastasectomy for colorectal cancer between 1990 and 2008. RESULTS: Among the 339 patients, 191 experienced recurrence, 77 received DLT for recurrence, 38 had a PFS of 2 years or longer after the treatment, and 33 had maintained a PFS at the last follow-up date. The patients had PFS ranging from 39 to 212 months (median, 101 months). The 5-year OS, PFS, and TTIR rates were respectively 63.4%, 42.2%, and 51.9%. The TTIR curve was similar to the OS curve 7 years after the initial metastasectomy. The difference between TTIR and PFS at 7 years was 9.7%, indicating probability of cure by repeat DLT. Multivariable analysis showed different prognostic factors among OS, PFS, and TTIR. CONCLUSION: At the initial metastasectomy, TTIR may reflect probability of a cure, including cure by repeat DLT, and can be used to analyze prognostic factors associated with cure.

Prognostic impact of the tumor volume doubling time in clinical T1 non-small cell lung cancer with solid radiological findings.

BACKGROUND: The purpose of this study was to investigate better radiological prognostic factors in clinical T1 pure-solid non-small cell lung cancer (NSCLC). METHODS: This study enrolled 284 patients with clinical T1 solid NSCLC who underwent anatomical lung resection. The Cox proportional hazard model was used to evaluate the prognostic impact of tumor volume doubling time (VDT) at disease-free survival (DFS) and cancer-specific survival (CSS). RESULTS: The median VDT was 347 days. Age (hazard ratio (HR) = 1.04; 95% confidence interval (CI), 1.01-1.07) and standardized uptake value max (SUVmax) (>6.0) (HR = 2.61; 95% CI, 1.52-4.66) were identified as significantly independent worse prognostic factors for DFS in a multivariable analysis without VDT. Furthermore, a multivariable analysis without SUVmax identified age (HR = 1.06; 95% CI, 1.03-1.09), CEA (>5.0 ng/ml) (HR = 2.34; 95% CI, 1.30-4.02), tumor diameter on CT (>2.0 cm) (HR = 1.91; 95% CI, 1.18-3.13), and VDT (HR = 4.03; 95% CI, 2.41-6.93) as significantly independent worse prognostic factors for DFS. CONCLUSIONS: The VDT value could be a useful prognostic factor in clinical T1 solid NSCLC.

Prediction of lymph node metastasis of clinical stage IA non-small cell lung cancer based on the tumor volume doubling time.

PURPOSE: To investigate whether the volume doubling time is a preoperative predictor of lymph node metastasis of clinical stage IA non-small cell lung cancer (NSCLC). METHODS: The subjects of this retrospective study were 204 patients who underwent lobectomy and mediastinal lymph node dissection for clinical stage IA NSCLC. We analyzed the relationship between lymph node metastasis and clinicopathological factors, including the volume doubling time. RESULTS: Lymph node metastasis developed in 24 (11.8%) patients. Multivariable analysis identified consolidation diameter (Odds ratio = 1.407; 95% confidence interval, 1.007-1.966, p = 0.046) and the solid-part tumor volume doubling time (Odds ratio = 0.982; 95% confidence interval, 0.973-0.991, p < 0.001) as independent predictors of lymph node metastasis. The combination of a larger consolidation diameter (> 1.9 cm) and a shorter solid-part tumor volume doubling time (< 132 days) had sensitivity, specificity, and accuracy of 79.2%, 94.4%, and 92.6%, respectively. CONCLUSIONS: The consolidation diameter and solid-part tumor volume doubling time can be useful preoperative predictors of lymph node metastasis of clinical stage IA NSCLC.

[Carinal Resection and Reconstruction for Second Primary Lung Cancer Five Years After the Left Upper Lobectomy].

A tumor was detected at the tracheal carina to the orifice of the left main bronchus in a 66-year-old man who had undergone a left upper lobectomy for lung cancer five years before and was diagnosed as a squamous cell carcinoma. Carinal resection and reconstruction was performed because of the tumor relapse after the treatment by argon plasma coagulator. Carinal resection was performed under the median sternotomy with reconstruction by the montage method. The patient was discharged on the 8th postoperative day without any postoperative complications.

[Diffuse Pulmonary Meningotheliomatosis Needed to be Differentiate from Metastatic Lung Tumor:Report of a Case].

A 77-year-old woman was found to have multiple granular shadows in the bilateral lungs and a right mammary mass on chest computed tomography (CT) scan for preoperative check of colorectal cancer. The right mammary mass was diagnosed as breast cancer as a result of vacuum-assisted breast biopsy. Fluorodeoxyglucose-positron emission tomography( FDG-PET) showed no abnormal uptake in the lung fields. Since a transbronchial lung biopsy did not establish a diagnosis, an incisional biopsy was performed via a thoracoscopic approach. The histology of the pulmonary nodules revealed minute pulmonary meningothelial-like nodules (MPMNs) and the patient was diagnosed with diffuse pulmonary meningotheliomatosis (DPM). When multiple pulmonary nodules are found in patients with coexisting malignancy, DPM should be considered in addition to metastatic lung tumors.

[Growing Mixed Squamous Cell and Glandular Papilloma Difficult to Differentiate from Primary Lung Cancer:Report of a Case].

A 76-year-old woman was referred to our hospital due to abnormal chest radiography findings. Chest computed tomography (CT) revealed a nodule in the right lower lobe. Fluorodeoxyglucose-positronemission tomography (FDG-PET) showed abnormal accumulation in the nodule. Bronchoscopy did not provide a definitive diagnosis. Since the nodule tended to increase in size, primary lung cancer was suspected and surgery was performed. During the surgery, pathological diagnosis of squamous cell carcinoma was made, and a right lower lobectomy was performed. Subsequently, a pathological diagnosis of mixed squamous cell and glandular papilloma (mixed papilloma) was made. She has had no sign of recurrence for approximately four years since the surgery.

Correlates of lifetime and past one-year HIV-testing experience among men who have sex with men in Japan.

This study aimed to examine correlates of lifetime and past-year HIV testing among men who have sex with men (MSM) in Japan. A unique, anonymous online self-report survey was conducted in 2015. A total of 776 participants completed the survey and answered questions on sociodemographic information, HIV-testing experience, history of syphilis, experience talking about HIV, recognition of AIDS-related community-based organization (CBO) materials, and sex behaviors. HIV-testing experience and related factors were assessed for two groups: regional cities and Tokyo and Osaka. A Poisson regression analysis revealed that higher lifetime HIV testing was associated with older age, previous syphilis diagnosis, and experience talking about HIV. Moreover, higher HIV testing in the past year was associated with experience talking about HIV with friends and recognition of HIV-related CBO materials. Increased dissemination of HIV-related information provided by CBOs may, therefore, be an effective prevention policy intervention targeted at Japanese MSM to promote regular testing and maintain their interest in HIV issues.

Surgical challenges in multimodal treatment of N2-stage IIIA non-small cell lung cancer.

Locally advanced non-small cell lung cancer, especially mediastinal lymph node metastasis-positive stage IIIA-N2 cancer, is a heterogeneous disease state characterized by anatomically locally advanced disease with latent micrometastases. Thus, surgical resection or radiotherapy alone has historically failed to cure this disease. During the last three decades, persistent efforts have been made to develop a suitable treatment modality to overcome these problems using chemotherapy and/or radiotherapy with surgical resection. However, the role of surgical resection remains unclear, and the standard treatment for stage IIIA-N2 disease is concurrent chemoradiotherapy. In general, adjuvant chemotherapy is indicated for completely resected pathological stage IB disease or lymph node metastasis-positive pathological stage II or IIIA disease. Platinum-based doublet cytotoxic chemotherapy is currently the standard regimen. Additionally, post-operative radiotherapy might be indicated for post-operatively proven mediastinal lymph node metastasis; i.e. clinical N0-1 and pathological N2 disease. With the remarkable progression that has recently been made in the field of chemotherapy, such as advances in molecular targeting agents and immune checkpoint inhibitors, the basic policy of chemotherapy has been shifting to personalized treatment based on the individual patient's oncogene driver mutation status, immune status and other parameters. The same trend is being seen in the treatment of stage IIIA-N2 disease. We should consider the past and upcoming results of several clinical trials to optimize the coming era of personalized treatment.

Recent advances and future perspectives in adjuvant and neoadjuvant immunotherapies for lung cancer.

The superior efficacy of immune checkpoint inhibitors for the treatment of advanced non-small cell lung cancer has inspired many clinical trials to use immune checkpoint inhibitors in earlier stages of lung cancer worldwide. Based on the theoretical feasibility that neoantigens derived from a tumor tissue are present in vivo, some clinical trials have recently evaluated the neoadjuvant, rather than the adjuvant, use of immune checkpoint inhibitors. Some of these trials have already produced evidence on the safety and efficacy of immune checkpoint inhibitors in a neoadjuvant setting, with a favorable major pathologic response and few adverse events. In the most impactful report from Johns Hopkins University and the Memorial Sloan Kettering Cancer Center, the programed death-1 inhibitor nivolumab was administered to 21 patients in a neoadjuvant setting. The authors reported a major pathologic response rate of 45%, with no unexpected delay of surgery related to the adverse effects of nivolumab. The adjuvant as well as the neoadjuvant administration of immune checkpoint inhibitors has also been considered in various clinical trials, with or without the combined use of chemotherapy or radiotherapy. The development of appropriate biomarkers to predict the efficacy of immune checkpoint inhibitors is also underway. The expression of programed death ligand-1 and the tumor mutation burden are promising biomarkers that have been evaluated in many settings. To establish an appropriate method for using immune checkpoint inhibitors in combination with surgery, the Lung Cancer Surgical Study Group of the Japan Clinical Oncology Group will manage clinical trials using a multimodality treatment, including immune checkpoint inhibitors and surgery.

Prognostic significance of propofol-based intravenous anesthesia in early-stage lung cancer surgery.

PURPOSE: The purpose of this study was to assess whether the anesthetic type is associated with the prognosis of pathological stage I non-small cell lung cancer (NSCLC). METHODS: Clinicopathological data from 431 consecutive patients who underwent lobectomy for NSCLC between 2010 and 2016 were collected. Patients were classified into groups according to the type of anesthesia: propofol-based total intravenous anesthesia (TIVA) or inhalation anesthesia (INHA). We investigated the prognostic differences between these two groups. RESULTS: A total of 72 patients in the TIVA group and 158 patients in the INHA group were eligible for the analysis. Recurrence was observed in 4 (5.6%) patients in the TIVA group and 19 (12.0%) patients in the INHA group (P = 0.159), and all-cause death occurred in 4 (5.6%) patients in the TIVA group and 24 (15.2%) patients in the INHA group (P = 0.049). The 5-year recurrence-free survival (RFS) and overall survival rates of the TIVA/INHA groups were 91.7%/77.4% and 94.4%/83.5%, respectively. TIVA was associated with a significantly better prognosis. A multivariable analysis of factors associated with RFS revealed that the type of anesthesia as a significant prognostic factor (P = 0.047). CONCLUSION: Propofol-based TIVA was associated with a better prognosis in comparison to INHA in patients with surgically resected pathological stage I NSCLC.

[Outcomes of Sublobar Resection for the Patients with a Metachronous Multiple Lung Cancer].

OBJECTIVES: In order to perform appropriate treatment for metachronous multiple lung cancer, it is important to verify the surgical treatment outcome. We evaluated the surgical outcome of metachronous multiple lung cancer focused on the sublobar resection of metachronous second lung cancer. METHODS: The subjects of this study were 1,513 cases that underwent radical resection for primary lung cancer in our institution from January 2004 to April 2020. We selected 23 (1.5%) patients who underwent lobectomy for initial primary lung cancer and underwent sublobar resection for metachronous second lung cancer. RESULTS: The median follow-up period from resection for initial primary lung cancer to resection for metachronous second lung cancer was 49 months. Regarding the analyses for survival, the median follow-up period after resection for initial primary lung cancer was 79 months with a five-year overall survival rate of 80.4% and a five-year relapse-free survival rate of 75.6%. Whereas the median follow-up period after resection for metachronous second lung cancer was 27 months with a five-year overall survival rate of 55.8% and a five-year relapse-free survival rate was 48.4%. CONCLUSIONS: The long-term outcome for sublobar resection for metachronous second lung cancer was similar to previous reports and the rate of complications tended to be low.

[Congenital Defect of the Pericardium Incidentally Found during Surgery for Lung Cancer:Report of a Case].

A 78-year-old man was admitted to our hospital for further examination of a mass shadow in the left lower lobe noted on chest computed tomography. Because lung cancer was suspected, a left lower lobectomy was performed. During surgery, the left lower lobe and heart were so tightly adherent that the pericardial defect was not initially perceivable. As we proceeded with adhesion detachment, we discovered that the left lower lobe and the myocardium were directly adherent to one another through a complete defect of the pericardium, which required very careful surgical technique. Because of the complete defect of the pericardium, we considered the risk of heart failure to be low and accordingly did not perform a repair. The postoperative course was uneventful.

[Mediastinal Dedifferentiated Liposarcoma Resected with Partial Resection of Pericardium].

An anterior mediastinal tumor was detected by computed tomography (CT) in a 66-year-old man who complained of left flank pain, and the surgical treatment was performed. At surgery, partial resection of the pericardium was also conducted because the pericardial inversion was suspected. The histopathological diagnosis was dedifferentiated liposarcoma. The patient is well without adjuvant chemotherapy 23 months after the surgery.

[Lung Abscess by Drug-resistant Pseudomonas Aeruginosa Necessary to Differentiate from Lung Cancer:Report of a Case].

A 64-year-old man visited our hospital because of an abnormal shadow on an annual health check-up. Chest computed tomography demonstrated a nodule 22 mm in size in the right lung. 18-F fluorodeoxyglucose positron emission tomography showed abnormal accumulation in the nodule. Since lung cancer was suspected, a right wedge resection was performed. Pathological examination showed no malignant findings in the nodule. The diagnosis of lung abscess by drug resistance Pseudomonas aeruginosa was made by the pus culture and the postoperative course was uneventful.