Impact of smoking in resected lung cancer depends on epidermal growth factor receptor mutation.

OBJECTIVES: Smokers comprise majority of surgical patients with primary lung cancer. Epidermal growth factor receptor (EGFR) mutation-negative status impacts the treatment of recurrence. However, the prognostic impact of cigarette smoking stratified by EGFR mutation status has not been reported, we assessed this impact in patients with resected lung cancer. METHODS: We retrospectively analyzed 362 consecutive patients who underwent complete resection for stage I primary lung cancer at our institution between 2012 and 2021. The EGFR mutation status was evaluated using real-time polymerase chain reaction. We compared the overall survival (OS) and disease-free survival (DFS) between patients with and without a smoking history. RESULTS: The EGFR mutation-negative group included 194 patients, of whom 160 (83%) had a smoking history. Male sex (p < 0.01), forced expiratory volume in 1 s (p < 0.01), and adenocarcinoma (p < 0.01) showed significant differences between the groups. In the EGFR mutation-positive group, the 5-year OS and DFS were similar regardless of smoking status (OS: 86% vs 75%, DFS: 73% vs 73%). In the EGFR mutation-negative group, the 5-year OS and DFS were significantly poorer in the smoking group (OS: 87% vs 65%, p = 0.05; DFS: 84% vs 54%, p = 0.01). Mortality from other diseases was relatively high (n = 19, 53%). CONCLUSIONS: Cigarette smoking might be associated with a poor prognosis in EGFR mutation-negative lung cancer but had no impact on the prognosis of EGFR mutation-positive group. This finding underscores the potential influence of smoking on the treatment of lung cancer recurrence but also highlights its significance in contributing to mortality from other diseases.

Wild-Type Anaplastic Lymphoma Kinase Expression in Solitary Pulmonary Nodules: A Potential Marker for Primary Lung Squamous Cell Carcinoma in Patients With Previous Neck Squamous Cell Carcinoma.

In patients with a history of head and neck squamous cell carcinoma (HNSCC), distinguishing between primary lung squamous cell carcinoma (LSCC) and pulmonary metastasis of HNSCC is critical when a solitary pulmonary nodule is observed. However, differentiation in clinical practice remains challenging because no golden-standard immunohistochemical (IHC) marker has been established to identify the primary organ of squamous cell carcinoma (SCC). The anaplastic lymphoma kinase (ALK) gene harbors rearrangements in approximately 4-6% of non-small cell lung cancer (NSCLC) cases. The detection of ALK rearrangements is well-established through anti-ALK IHC. While anti-ALK IHC is primarily positive in adenocarcinoma within NSCLC, wild-type ALK without rearrangements is occasionally detected in other histological types, such as SCC. We report two surgical cases with a history of laryngeal cancer that exhibited solitary pulmonary SCC, in which only the lung lesions demonstrated positivity for wild-type ALK through IHC and fluorescence in-situ hybridization method, allowing for the diagnosis of primary LSCC and following postoperative strategy.

Prognostic potential of lipid profiling in cancer patients: a systematic review of mass spectrometry-based studies.

Cancer prognosis remains a critical clinical challenge. Lipidomic analysis via mass spectrometry (MS) offers the potential for objective prognostic prediction, leveraging the distinct lipid profiles of cancer patient-derived specimens. This review aims to systematically summarize the application of MS-based lipidomic analysis in prognostic prediction for cancer patients. Our systematic review summarized 38 studies from the past decade that attempted prognostic prediction of cancer patients through lipidomics. Commonly analyzed cancers included colorectal, prostate, and breast cancers. Liquid (serum and urine) and tissue samples were equally used, with liquid chromatography-tandem MS being the most common analytical platform. The most frequently evaluated prognostic outcomes were overall survival, stage, and recurrence. Thirty-eight lipid markers (including phosphatidylcholine, ceramide, triglyceride, lysophosphatidylcholine, sphingomyelin, phosphatidylethanolamine, diacylglycerol, phosphatidic acid, phosphatidylserine, lysophosphatidylethanolamine, lysophosphatidic acid, dihydroceramide, prostaglandin, sphingosine-1-phosphate, phosphatidylinosito, fatty acid, glucosylceramide and lactosylceramide) were identified as prognostic factors, demonstrating potential for clinical application. In conclusion, the potential for developing lipidomics in cancer prognostic prediction was demonstrated. However, the field is still nascent, necessitating future studies for validating and establishing lipid markers as reliable prognostic tools in clinical practice.

Impact of central nervous system metastasis after complete resection of lung adenocarcinomas harboring common EGFR mutation - A real-world database study in Japan: The CReGYT-01 EGFR study.

OBJECTIVES: To clarify the impact of central nervous system (CNS) metastasis on performance status (PS) at relapse, on subsequent treatment(s), and on survival of patients with lung adenocarcinoma harboring common epidermal growth factor receptor (EGFR) mutation. METHODS: We conducted the multicenter real-world database study for patients with radical resections for lung adenocarcinomas between 2015 and 2018 at 21 centers in Japan. EGFR mutational status was examined at each center. RESULTS: Of 4181 patients enrolled, 1431 underwent complete anatomical resection for lung adenocarcinoma harboring common EGFR mutations. Three-hundred-and-twenty patients experienced disease relapse, and 78 (24%) had CNS metastasis. CNS metastasis was significantly more frequent in patients with conventional adjuvant chemotherapy than those without (30% vs. 20%, P = 0.036). Adjuvant chemotherapy did not significantly improve relapse-free survival at any pathological stage (adjusted hazard ratio for stage IA2-3, IB, and II-III was 1.363, 1.287, and 1.004, respectively). CNS metastasis did not affect PS at relapse. Subsequent treatment, mainly consisting of EGFR-tyrosine kinase inhibitors (TKIs), could be equally given in patients with or without CNS metastasis (96% vs. 94%). Overall survival after relapse was equivalent between patients with and without CNS metastasis. CONCLUSION: The efficacy of conventional adjuvant chemotherapy may be limited in patients with lung adenocarcinoma harboring EGFR mutations. CNS metastasis is likely to be found in practice before deterioration in PS, and may have little negative impact on compliance with subsequent EGFR-TKIs and survival after relapse. In this era of adjuvant TKI therapy, further prospective observational studies are desirable to elucidate the optimal management of CNS metastasis.

Intrapulmonary solitary fibrous tumor with malignant potential: A case report.

Intrapulmonary solitary fibrous tumor is rare, and its clinical course has not been sufficiently reported. We presented a case of an 80-year-old male non-smoker and discussed the surgical procedure selection and the recurrence risk assessment. A solid nodule, 1.1 cm in diameter, was identified in the left lower lobe on chest computed tomography and showed no accumulation on positron emission tomography. A wedge resection with a sufficient surgical margin under video-assisted thoracoscopic surgery was performed. Based on histological morphology and immunohistochemical examination, this case was considered an intrapulmonary solitary fibrous tumor with malignancy potential, requiring cautious follow-up observation.

Evaluation of a bundle approach for the prophylaxis of ventilator-associated pneumonia: A retrospective single-center Study.

Ventilator-associated pneumonia (VAP) is defined as pneumonia occurring after the first 48 hours of intubation and mechanical ventilation and is the most frequent hospital-acquired infection associated with intensive care unit (ICU) admissions. Herein, we defined a novel VAP bundle including 10 preventive items. We analyzed compliance rates and clinical effectiveness associated with this bundle in patients undergoing intubation at our medical center. A total of 684 consecutive patients who underwent mechanical ventilation were admitted to the ICU between June 2018 and December 2020. VAP was diagnosed by at least two physicians based on the relevant United States Centers for Disease Control and Prevention criteria. We retrospectively evaluated associations between compliance and VAP incidence. The overall compliance rate was 77%, and compliance generally remained steady during the observation period. Moreover, although the number of ventilatory days remained unchanged, the incidence of VAP improved statistically significantly over time. Low compliance was identified in four categories: head-of-bed elevation of 30- 45º, avoidance of oversedation, daily assessment for extubation, and early ambulation and rehabilitation. The incidence of VAP was lower in those with an overall compliance rate of ≥ 75% than its incidence in the lower compliance group (15.8 vs. 24.1%, p = 0.018). When comparing low-compliance items between these groups, we found a statistically significant difference only for daily assessment for extubation (8.3 vs. 25.9%, p = 0.011). In conclusion, the evaluated bundle approach is effective for the prophylaxis of VAP and is thus eligible for inclusion in the Sustainable Development Goals.

Lipid biomarkers that reflect postoperative recurrence risk in lung cancer patients who smoke: a case-control study.

BACKGROUND: The risk of postoperative recurrence is higher in lung cancer patients who smoke than non-smokers. However, objective evaluation of the postoperative recurrence risk is difficult using conventional pathological prognostic factors because of their lack of reproducibility. Consequently, novel objective biomarkers that reflect postoperative risk in lung cancer patients who smoke must be identified. Because cigarette smoking and oncogenesis alter lipid metabolism in lung tissue, we hypothesized that the lipid profiles in lung cancer tissues are influenced by cigarette smoking and can reflect the postoperative recurrence risk in smoking lung cancer patients. This study aimed to identify lipid biomarkers that reflect the smoking status and the postoperative recurrence risk. METHODS: Primary tumor tissues of lung adenocarcinoma (ADC) (n = 26) and squamous cell carcinoma (SQCC) (n = 18) obtained from surgery were assigned to subgroups according to the patient's smoking status. The ADC cohort was divided into never smoker and smoker groups, while the SQCC cohort was divided into moderate smoker and heavy smoker groups. Extracted lipids from the tumor tissues were subjected to liquid chromatography-tandem mass spectrometry analysis. Lipids that were influenced by smoking status and reflected postoperative recurrence and pathological prognostic factors were screened. RESULTS: Two and 12 lipid peaks in the ADC and SQCC cohorts showed a significant positive correlation with the Brinkman index, respectively. Among them, in the ADC cohort, a higher lipid level consisted of three phosphatidylcholine (PC) isomers, PC (14:0_18:2), PC (16:1_16:1), and PC (16:0_16:2), was associated with a shorter recurrence free period (RFP) and a greater likelihoods of progressed T-factor (≥ pT2) and pleural invasion. In the SQCC cohort, a lower m/z 736.5276 level was associated with shorter RFP and greater likelihood of recurrence. CONCLUSIONS: From our data, we propose three PC isomers, PC (14:0_18:2), PC (16:1_16:1), and PC (16:0_16:2), and a lipid peak of m/z 736.5276 as novel candidate biomarkers for postoperative recurrence risk in lung ADC and SQCC patients who are smokers.

Thyroid transcription factor-1 expression in rectal adenocarcinoma metastatic to the lung.

Distinguishing metastatic lung tumors from primary lung cancer is essential for planning the appropriate treatment strategy. Thyroid transcription factor-1 (TTF-1) is a reliable immunohistochemistry (IHC) marker for differentiating between primary lung adenocarcinomas and metastatic lung tumors originating from colorectal adenocarcinomas. Herein, we report a rare case of TTF-1 expression in both the metastatic lung tumor and primary rectal adenocarcinoma. Aside from the similar histological characteristics of both tumors when stained with hematoxylin-eosin, the IHC patterns, including negative results for alveolar epithelium markers (napsin A and CK7) and positive results for intestinal markers (CK20, CDX2, SATB2, and ß-catenin), of the lung tumor and the primary rectal adenocarcinoma strongly supported the final diagnosis. Considering the non-negligible frequency of TTF-1 positivity in colorectal adenocarcinomas, applying the IHC panel including multiple markers for alveolar epithelium and intestinal differentiation, would be helpful to support the diagnosis of metastatic lung tumor from a rectal adenocarcinoma.

Left upper lobectomy with combined distal aortic arch and left subclavian artery resection after neoadjuvant chemoradiotherapy for locally advanced lung squamous cell carcinoma.

T4 locally advanced non-small cell lung cancer (NSCLC) is a heterogeneous group with a great variety of involved organs and is associated with a poor prognosis. However, appropriately selected patients benefit from surgical resection. The surgical indication must be carefully considered based on the risk-benefit between high surgical stress and expected prognosis, particularly in cases with probable aortic involvement. Here, we report a long-term survival case of left upper lobe squamous cell carcinoma, in which lobectomy and combined distal aortic arch and left subclavian artery resection achieved a complete resection after induction chemoradiotherapy (CRT). Appropriate patient selection considering expected prognosis, induction CRT and complete resection under well-planned cardiopulmonary bypass are essential to achieve a long-term survival on T4 NSCLC with a probable aortic involvement.

Poor prognosis of patients with severe COVID-19 admitted to an infectious disease intensive care unit during the pandemic caused by the Delta variant in Japan.

During the surge of coronavirus disease (COVID-19) caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) delta variant, our institution operated an intensive care unit (ICU) for patients with severe COVID-19. The study aim was to determine the survival rate and treatment outcomes of patients with severe COVID-19 treated in the ICU during the surge. A total of 23 consecutive patients with severe COVID-19 were admitted to the ICU between August 5 and October 6, 2021. Patients received multidrug therapy consisting of remdesivir, tocilizumab, heparin, and methylprednisolone. The patients were divided into two groups based on the ordinal scale (OS): a non-invasive oxygen therapy (OS-6) group, and an invasive oxygen therapy (OS-7) group. There were 13 (57%) and 10 (43%) patients in the OS-7 and OS-6 groups, respectively. All patients were unvaccinated. Sixteen patients (70%) were male. The median age was 53 years; the median body mass index (BMI) was 30.3 kg/m2; and the median P/F ratio on admission was 96. The 30-day survival rate was 69% and was significantly poorer in the OS-7 group (54%) than in the OS-6 group (89%; p = 0.05). The prevalence of obesity (p = 0.05) and the Sequential Organ Failure Assessment (SOFA) score on admission (p < 0.01) were significantly higher in the OS-7 group. Seven patients in the OS-7 group (54%) developed bacteremia. A low P/F ratio on admission was a significant unfavorable prognostic factor (hazard ratio: 10.9; p = 0.03). The survival rate was poor, especially in patients requiring invasive oxygen therapy. More measures are needed to improve the treatment outcomes of patients with severe COVID 19.

Autopsy findings of a patient with severe COVID-19 treated with long-term extracorporeal membrane oxygenation.

Extracorporeal membrane oxygenation (ECMO) therapy in patients with coronavirus disease 2019 (COVID-19) has a low frequency of use, and thus pathological findings in such patients are valuable. In this case report, a 62-year-old man with a history of hypertension presented with a runny nose. After an at-home COVID-19 positive test, he developed dyspnea and fever. Once admitted to our hospital, his oxygenation worsened, and ECMO was initiated. He died from respiratory failure 69 days after ECMO induction. Macroscopically, the lungs gained mass, were partially consolidated, and were airless. Histological analysis revealed diffuse bronchial epithelial metaplasia and adenoid metaplasia in the alveolar epithelium. Although the lung parenchyma was partially preserved, there was organizing and fibrosis that filled pulmonary alveolus due to COVID-19 and changes resulting from disuse and long-term ECMO.

Loss of GSTO2 contributes to cell growth and mitochondria function via the p38 signaling in lung squamous cell carcinoma.

Glutathione S-transferase omega 2 (GSTO2) lacks any appreciable GST activity, but it exhibits thioltransferase activity. The significance of GSTO2 in lung function has been reported; however, the precise expression and molecular function of GSTO2 in the lungs remain unclear. In the present study, we found that GSTO2 is expressed in airway basal cells, non-ciliated, columnar Clara cells, and type II alveolar cells, which have self-renewal capacity in the lungs. Contrastingly, no GSTO2 expression was observed in 94 lung squamous cell carcinoma (LSCC) samples. When human LSCC cell lines were treated with 5-aza-2'-deoxycytidine, a DNA-methyltransferase inhibitor, GSTO2 transcription was induced, suggesting that aberrant GSTO2 hypermethylation in LSCC is the cause of its downregulation. Forced GSTO2 expression in LSCC cell lines inhibited cell growth and colony formation in vitro. In a subcutaneous xenograft model, GSTO2-transfected cells formed smaller tumors in nude mice than mock-transfected cells. Upon intravenous injection into nude mice, the incidence of liver metastasis was lower in mice injected with GSTO2-transfected cells than in those injected with mock-transfected cells. In addition, GSTO2 induction suppressed the expression of ß-catenin and the oxygen consumption rate, but it did not affect the extracellular acidification rate. Furthermore, GSTO2-transfected cells displayed lower mitochondrial membrane potential than mock-transfected cells. When GSTO2-transfected cells were treated with a p38 inhibitor, ß-catenin expression and mitochondrial membrane potential were recovered. Our study indicated that the loss of GSTO2 via DNA hypermethylation contributes to the growth and progression of LSCC, probably by modulating cancer metabolism via the p38/ß-catenin signaling pathway.

Prognostic impact of home oxygen therapy on patients with resected non-small-cell lung cancer with interstitial lung disease.

PURPOSE: Non-small-cell lung cancer (NSCLC) patients with interstitial lung disease (ILD) have a poor prognosis. The present study evaluated the prognostic impact of home oxygen therapy (HOT) in NSCLC patients with ILD. METHODS: Overall, 3099 consecutive patients underwent complete resection of stage IA to IIIA NSCLC at our institution between 2002 and 2016. ILD was diagnosed and categorized based on high-resolution computed tomography. The criteria for HOT included less than 90% resting oxygen saturation in the peripheral arteries and severe exertional dyspnea. We retrospectively compared the overall survival between ILD patients with and without HOT. RESULTS: ILD was observed in 150 (5%) patients. Seventeen (11%) patients needed HOT at discharge. The incidences of usual interstitial pneumonia (UIP) pattern (p = 0.03) and blood loss (p < 0.01) were significantly higher in the patients requiring HOT than in those without HOT. Significantly more patients developed complications (p = 0.04) in the HOT group than in the non-HOT group, with three (18%) having acute exacerbations. The 3-year overall survival rate was significantly lower in the HOT patients than in those without HOT (28% vs. 63%, p = 0.03). CONCLUSIONS: Patients requiring postoperative HOT showed a significantly poorer prognosis after complete resection than those without HOT. Therefore, the indication for surgery should be investigated cautiously in order to prevent the need for postoperative HOT.

Video-assisted thoracoscopic right upper lobectomy in a patient with a displaced bronchus and vascular abnormalities.

Bronchial abnormalities are rare, and they are infrequently associated with pulmonary vascular abnormalities. It is important to identify such abnormal anatomical structures before lobectomy of the lung under thoracoscopy. There have been only three reports on video-assisted thoracoscopic lobectomy in patients with anomalous bronchi and vascular abnormalities to date. Here, we present a report of video-assisted thoracoscopic right upper lobectomy performed in a patient with bronchial and vascular abnormalities. Both preoperative imaging and intraoperative findings revealed a displaced anomalous B2 bronchus arising from the bronchus intermedius, as well as abnormal distribution of the aberrant vein V2 draining into vein V6 . It is critical to understand the precise anatomical structures preoperatively to perform video-assisted thoracoscopic pulmonary lobectomy safely.

Ectopic intrapulmonary follicular adenoma diagnosed by surgical resection.

Ectopic intrapulmonary thyroid tissue is extremely rare and considerably difficult to diagnose without surgery. Ectopic thyroid tissue, described as a mediastinal tumor, and intrapulmonary lesions are infrequent. An abnormal shadow was detected upon chest X-ray in a 60-year old woman with a history of benign thyroid goiter. A computed tomography scan revealed a solitary nodule measuring 27 mm in diameter in the left lower lobe, the diameter of which had increased by 5 mm since initial observation eight years ago. A thoracoscopic wedge resection was performed and the lesion was determined to be a non-invasive, soft-tissue tumor. It was pathologically diagnosed as an ectopic thyroid follicular adenoma. The course of the tumor was uneventful. A diagnosis of ectopic intrapulmonary thyroid should be made cautiously and only after ruling out metastasis of a follicular adenoma or thyroid carcinoma. This diagnosis of ectopic thyroid tissue was made possible by the surgical approach.

Thoracoscopic right middle lobectomy for Mycobacterium abscessus in a young patient suspected of having congenital immunodeficiency.

Mycobacterium abscessus (M. abscessus) infection is resistant to multi-antibacterial treatment, and surgical resection is often recommended. We report a case of M. abscessus infection in a young patient suspected of having a GATA2 mutation. A 19-year-old woman with a medical history of severe sinusitis and a family history of non-tuberculous mycobacteriosis presented at our hospital. M. abscessus was confirmed by sputum culture. The patient received multidrug therapy, including clarithromycin. CT scan demonstrated bronchodilation and capacity decrease due to non-obstructive atelectasis in the middle lobe. We performed thoracoscopic resection without complications. Congenital immunodeficiency was suspected given the patient's past medical and family history. The result of lymphocyte subset analysis revealed a GATA2 mutation, but no genetic mutation was detected by a next-generation sequencer. The patient followed a good clinical course. This paper reports the successful treatment of an M. abscessus infection and the importance of checking the genetic background of young patients.

Fluorescence navigation with indocyanine green for identification of intersegmental planes using a photodynamic eye camera.

BACKGROUND: Pulmonary segmentectomy is an important surgical option for complete resection in patients with poor lung function. However, correctly recognizing the intersegmental plane for accurate segmentectomy is sometimes difficult. We therefore developed a novel method that allows the detection of intersegmental planes using an indocyanine green (ICG) fluorescence imaging device, photodynamic eye (PDE) camera, PDE-neo. METHODS: As a prospective study, we performed bronchial ICG-guided segmentectomy using PDE-neo. The patients were placed in a lateral position under general anesthesia, and we performed a combined muscle-sparing minithoracotomy with video assistance. The pulmonary artery, pulmonary vein, and segmental bronchi were separated, and ICG mixed with autologous blood was introduced by spraying through the resected segment bronchi to enable visualization of the intersegmental surface with PDE-neo. This study protocol was approved by the Research Ethics Board of Hamamatsu University School of Medicine, Japan. Written informed consent was obtained from all patients. RESULTS: Overall, 10 lung malignancy patients, including 8 males and 2 females, participated in this study from March 2011 to October 2013. The median age was 69 years (range, 29-76 years). Pathologic diagnoses were 7 adenocarcinomas, 1 adenosquamous carcinoma, 1 carcinoid tumor, and 1 lung metastasis from the parotid gland cancer. The intersegmental planes of 8 cases could be identified by this method using a PDE-neo, whereas those of 2 cases did not show clear demarcations. The reason was that because of severe emphysema, air flowed from the resected segment to the surrounding segments, obliterating the demarcation between the two segmental planes. There were no recurrent cases and only two deaths due to other diseases were observed; and the 5-year cause-specific survival rate was 100%. CONCLUSIONS: Intersegmental planes could be more easily identified using ICG fluorescence imaging during segmentectomy. This method is feasible and effective and has a good long-term prognosis.

A case of diffuse pulmonary lymphangiomatosis with a venous anomaly presenting with acute respiratory failure and hemoptysis.

Diffuse pulmonary lymphangiomatosis (DPL) is a rare lymphatic disease that can cause diverse respiratory symptoms. A 22-year-old man, whose chest CT had shown an abnormality for years, presented with acute respiratory failure due to the abrupt onset of hemoptysis. The diagnosis of DPL was confirmed by surgical lung biopsy and lymphangiography. Histopathological investigation showed dilated vascular and lymphatic vessels. DPL can cause acute and life-threatening symptoms during its chronic clinical course. A coexisting anomaly in the venous system may be present in DPL patients with hemoptysis.

Case of Rapid Formation of Intraoperative Pulmonary Pneumatocele After Lobectomy.

Pulmonary pneumatocele that forms immediately after pulmonary resection is extremely rare. This report describes a case of pneumatocele that formed rapidly in the left lower lobe immediately after left upper lobectomy in a patient with lung cancer and emphysema. Massive and persistent air leakage through a chest tube was noted immediately after chest closure. Therefore, the chest was reopened, and the cyst wall was incised. The air leakage point was cauterized and covered with a polyglycolic acid sheet and fibrin glue. Herein, we report a rare case of newly developed pneumatocele immediately after lobectomy.