• FSTL1
• STAS
• TGF‐β1
• colorectal cancer
• follistatin‐like protein 1
• lung cancer
• metastasis
• organoid
• polarity
• spread through air spaces

• Lung Neoplasms/pathology
• Lung Neoplasms/secondary
• Lung Neoplasms/metabolism
• Lung Neoplasms/genetics
• Animals
• Humans
• Organoids/pathology
• Organoids/metabolism
• Cell Polarity
• Colorectal Neoplasms/pathology
• Colorectal Neoplasms/metabolism
• Mice
• Adenocarcinoma of Lung/pathology
• Adenocarcinoma of Lung/metabolism
• Cell Adhesion
• Transforming Growth Factor beta1/metabolism

• 21cm0106203h0006 Japan Agency for Medical Research and Development
• 18H02648 Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology in Japan
• 20H03772 Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology in Japan
• 20K08286 Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology in Japan
• 22K08982 Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology in Japan
• 23K07395 Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology in Japan
• Japan Agency for Medical Research and Development

• colorectal cancer
• laser-assisted pulmonary metastasectomy
• local recurrence
• spread through air spaces (STAS)

• cryo-embedding
• intraoperative decision-making
• lung cancer
• spread through air spaces lesions

• Humans
• Lung Neoplasms/diagnostic imaging
• Lung Neoplasms/surgery
• Lung/pathology
• Tomography, X-Ray Computed
• Radiosurgery

• non-small-cell lung cancer
• radiotherapy

• RS-2023-00232376, 1415187080 Korea Institute for Advancement of Technology (KIAT)

• Hepatocellular carcinoma
• Metastatic lung tumor
• Segmentectomy
• Three-dimensional computed tomography
• Tumor thrombus

• metastases/metastasectomy
• lung cancer
• diagnosis
• histology

Tumor spread through air spaces (STAS) in lung adenocarcinoma is a novel mechanism of invasion. STAS has been proposed as an independent predictor of poor prognosis. The aim of this study was to evaluate the correlations between STAS status and other clinicopathologic variables and to assess the prognostic implications of STAS and the distance from the edge of the tumor to the farthest STAS in patients with resected lung adenocarcinoma.

This is a single-institution retrospective observational study. We included all patients with resected lung adenocarcinoma from January 2017 to December 2018 at La Paz University Hospital. The cut-off for the distance from the edge of the tumor to the farthest STAS was 1.5 mm and was assessed by the area under the receiver operating characteristic curve.

A total of 73 patients were included. STAS was found in 52 patients (71.2%). Histological grade 3 (P = 0.035) and absence of lepidic pattern (P = 0.022) were independently associated with the presence of STAS. The median recurrence-free survival (RFS) was 48.06 months [95% confidence interval (CI) 33.58 months to not reached]. STAS-positive patients had shorter median RFS [39.23 months (95% CI 29.34-49.12 months)] than STAS-negative patients (not reached) (P = 0.04). STAS-positive patients with a distance from the edge of the tumor to the farthest STAS ≥1.5 mm had an even shorter median RFS [37.63 months (95% CI 28.14-47.11 months)]. For every 1 mm increase in distance, the risk of mortality increased by 1.26 times (P = 0.04).

Histological grade 3 and absence of lepidic pattern were independently associated with the presence of STAS. STAS was associated with a higher risk of recurrence. The distance from the edge of the tumor to the farthest STAS also had an impact on overall survival.

•

Lung adenocarcinoma patients with STAS had higher risk of recurrence.

• lung adenocarcinoma
• surgery
• tumor spread through air spaces

• colorectal cancer liver metastases
• cryoablation
• microwaves
• radiofrequency

• indications
• lung metastases
• pulmonary metastasectomy
• secondary lung cancer
• thoracic surgery
• wedge resections

• Chemotherapy
• Colorectal cancer
• Oligometastases
• Pulmonary metastases
• Radiotherapy
• Surgery

This study aimed to evaluate the role of anatomical resection (AR) in lung metastasectomy (LM) of colorectal cancer (CRC) and to investigate clinically relevant prognostic factors.

The medical records of 350 consecutive patients who underwent LM of CRC from 2011 to 2019 were reviewed. The patients were designated into AR group (lobectomy and segmentectomy), and non-anatomical resection (NAR) group (wedge resection), respectively. Kaplan–Meier method was used to analyze disease-free survival (DFS), pulmonary-specific disease-free survival (PDFS) and overall survival (OS). Cox proportional hazards regression model was performed to analyze the factors associated with DFS, PDFS and OS.

A total of 92 (31.2%) patients were enrolled in AR group and 203 (68.8%) in non-anatomical resection (NAR) group. AR significantly improved the 3-year DFS (64.1% vs 46.8%, HR 0.587, 95% CI 0.397–0.867, P = 0.007) and PDFS (75.0% vs 60.1%, HR 0.565, 95% CI 0.356–0.899, P = 0.016) compared with NAR. However, the extent of resection did not significantly impact the 3-year OS (AR 92.4% vs NAR 85.7%, HR 0.511, 95% CI 0.224–1.165, P = 0.110). In multivariate analysis, AR was identified as a protective factor for DFS (HR 0.576, 95% CI 0.356–0.934, P = 0.025) and PDFS (HR 0.631, 95% CI 0.409–0.973, P = 0.037). Preoperative abnormal CA19-9 was identified as the only prognostic factor for OS.

AR was superior to NAR for DFS and PDFS after LM from CRC.

• lobectomy
• prognosis
• pulmonary metastasis
• wedge resection

• Bronchoscopy
• Ground-glass opacity
• Localization
• Lung cancer
• Metastatic lung tumour

To demonstrate the feasibility and preliminary outcomes of a novel hybrid technique combining percutaneous microwave ablation and wire-assisted wedge resection for patients with multiple pulmonary metastases using intraoperative imaging.

We describe our technique and present a retrospective case series of 4 patients undergoing iCART at our institution between August 2018 and January 2020. Procedures were performed in a hybrid operating suite using the ARTIS Pheno cone beam computerized tomography scanner (Siemens Healthineers, Erlangen, German). Patient information included past history of malignancy as well as lesion size, depth, location, and histology result. Surgical complications and length of stay were also recorded.

Five procedures were performed on 4 patients during the study period. One patient underwent bilateral procedures 4 weeks apart. All patients underwent at least 1 ablation and 1 wedge resection during the combined procedure. Patient ages ranged from 40 to 66 years and the majority (75%) were men. All had a past history of cancer. Lesions were treated in every lobe. Size and depth ranged from 6 to 24 mm and 21 to 33 mm, respectively, for ablated nodules and 5 to 27 mm and 0 to 22 mm, respectively, for the wedge resected nodules. Three procedures were completed uniportal and operative time ranged from 51 to 210 minutes. All cases sustained <10 mL blood loss. There were 2 intraoperative pneumothorax, 1 prevented successful completion of the ablation. One patient required a prolonged period of postoperative physiotherapy and was discharged on day 6. The other patients were discharged on postoperative day 2 or 3. All 5 histology specimens confirmed metastatic disease.

Our hybrid approach provides a minimally invasive and comprehensive personalized therapy for patients with multiple pulmonary metastases under a single general anesthetic. It provides histology-based diagnosis whilst minimizing lung tissue loss and eliminating the need for transfer from radiology to operating theatre. Emergence of ablation as a treatment for stage 1 non–small cell lung cancer and the expansion of lung cancer screening may widen the application of iCART in the future.

• GGO, ground-glass opacity
• RFA, radiofrequency ablation
• hybrid surgery
• iCART, image-guided combined ablation and resection in thoracic surgery
• iVATS, image-guided video-assisted thoracoscopic surgery
• image-guided surgery
• metastatectomy
• microwave ablation
• pMWA, percutaneous microwave ablation
• pulmonary metastasis
• pulmonary nodule
• wedge resection

• Colorectal neoplasms
• Lung neoplasms
• Machine learning
• Radiology, interventional
• Tomography, X-ray computed

• Locoregional recurrence
• Mucinous tumor
• Mucus extension
• Pulmonary resection

Pulmonary metastasectomy (PM) is an established treatment that can provide improved long-term survival for patients with metastatic tumor(s) in the lung. In the current era, where treatment options other than PM such as stereotactic body radiation therapy (SBRT), immunotherapy, and molecular-targeted therapy are available, thoracic surgeons should review the approach to the preoperative evaluation and the indications. Preoperative evaluation consists of history and physical examinations, physiological tests, and radiological examinations. Radiological examinations serve to identify the differential diagnosis of the pulmonary nodules, evaluate their precise number, location, and features, and search for extra thoracic metastases. The indication of PM should be considered from both physiological and oncological points of view. The general criteria for PM are as follows; (I) the patient has a good general condition, (II) the primary malignancy is controlled, (III) there is no other extrapulmonary metastases, and (IV) the pulmonary lesion(s) are thought to be completely resectable. In addition to the general eligibility criteria of PM, prognostic factors of each tumor type should be considered when deciding the indication for PM. When patients have multiple poor prognostic factors and/or a short disease-free interval (DFI), thoracic surgeons should not hesitate to observe the patient for a certain period before deciding on the indication for PM. A multidisciplinary discussion is needed in order to decide the indication for PM.

• Pulmonary metastasectomy (PM)
• indication
• prognostic factor
• radiological examinations

Pulmonary metastasectomy has become an important part of the multimodality treatment. Surgical practice is based on observational studies published during the last decades, since no randomized clinical trials exist on the topic. However, the overall survival can be improved after pulmonary metastasectomy in carefully selected patients. The objective of resection of pulmonary metastases is to remove all tumor while preserving as much normal pulmonary parenchyma as possible and reduce invasiveness. Contrary, nonsurgical local treatment options for pulmonary metastases include thermal ablation techniques and stereotactic ablative body radiation. Thermal ablation techniques include microwave, cryotherapy and radiofrequency ablation. The present review article gives an overview on the topic and should help thoracic surgeons to make the right decisions in their daily practice.

• Pulmonary metastasectomy
• multimodal treatment
• palliative resection

• Pulmonary metastasis
• Surgical margin recurrence
• Wedge resection

Spread through air spaces (STAS) has recently been demonstrated to exhibit a negative impact on lung adenocarcinoma prognosis. However, most of these studies investigated STAS in nonmucinous adenocarcinoma. Here, we investigated the incidence of STAS in invasive mucinous adenocarcinoma (IMA) of the lung and evaluated whether tumor STAS was a risk factor of disease recurrence in IMA. We also examined clinicoradiologic factors in patients with IMA harboring STAS.

We reviewed pathologic specimens and imaging characteristics of primary tumors from 132 consecutive patients who underwent surgical resection for IMA to evaluate STAS. Patients with and without STAS were compared with respect to clinical characteristics as well as computed tomography (CT) imaging using logistic regression. The relationships between all variables including STAS and survival were analyzed.

Among a total of 132 patients, full pathologic specimens were available for 119 patients, and STAS was observed in 86 (72.3%). IMA patients with STAS were significantly associated with older age, presence of lobulated and spiculated margins on CT scan (P = 0.009, P = 0.006, and P = 0.027). In multivariate analysis for overall survival (OS), STAS was a borderline independent poor prognostic predictor (P = 0.028). Older age, history of smoking, higher T stage, presence of lymph node metastasis, and consolidative morphologic type remained independent predictors for OS.

STAS was associated with reduced OS and was a borderline independent poor prognostic factor in IMA. IMA with STAS was associated with older age and presence of lobulated and spiculated margins on CT scan.

Compared with other subtypes, IMA shows a higher incidence of STAS, which is an independent poor prognostic predictor even in IMA. Lobulated and spiculated margins on CT are associated with STAS.

Considering that STAS can carry the potential for aerogenous metastasis, predicting STAS using preoperative surrogate CT imaging is desirable to avoid limited resection.

• CT
• lung adenocarcinoma
• mucinous
• prognosis
• spread through air spaces

• Colorectal cancer
• Local recurrence
• Lung metastasectomy
• Spread through air spaces
• Surgical margin relapse

• Colorectal cancer
• Lung metastasectomy
• Outcomes
• Thoracotomy
• Video-assisted thoracoscopic surgery

• Colorectal cancer
• Lung metastasis
• Metastasectomy
• Outcome
• Surgery

• FDG-PET
• colorectal cancer
• pulmonary anatomical resection
• pulmonary metastasectomy
• pulmonary metastases
• thoracoscopy

The concept of spread through air spaces (STAS) has been described as a new form of invasion in the lung in the 2015 WHO classification of Lung Tumors, namely invasion through alveolar spaces. STAS is a prognostic factor independent of growth pattern and tumor stage, and it is also an independent risk factor for unfavorable prognosis of stage I lung adenocarcinoma (ADC) and stage I lung squamous cell carcinoma (SCC). The pathological characteristics are different between ADC and SCC. STAS is not reported as routine, so setting a unified pathological reading standard, and hunting for STAS as a regular reading process is urgently advocated. We write this review to investigate the research progress of STAS and its effects on the prognosis of lung cancer.

• STAS
• lung cancer
• pathological characteristics
• prognosis

• Pulmonary metastasis
• colorectal cancer
• recurrence
• video-assisted thoracoscopic surgery (VATS)

• GGN
• Localization
• Palpation
• Thoracoscopy
• VATS

• Adenocarcinoma
• Lung cancer
• Prognostic model
• Tumor spread through air spaces

• Oncology
• Surgery

• colorectal
• local recurrence
• metastasectomy
• wedge resection

• Colorectal cancer
• Elderly patients
• Lung metastases
• Metastasectomy
• Pulmonary metastases

In early‐stage lung adenocarcinomas, spread through air spaces (STAS) are reported to be a prognostic factor in patients who have undergone sublobar resection, but not lobectomy. In contrast, reports have also shown that STAS is significantly associated with poor survival outcomes after lobectomy, but not after limited resection. Thus, the prognostic impact of STAS differs according to published reports.

A total of 82 patients with early‐stage adenocarcinomas who underwent limited resection and whose STAS status could be examined were enrolled in this retrospective study. We evaluated the association between STAS and clinicopathological characteristics and postoperative survival.

Among 82 patients, 31 (37.8%) were positive for STAS, while 51 (62.2%) were negative. STAS was significantly associated with advanced tumor stage (P < 0.01), lower histological differentiation (P = 0.01), and the presence of pleural invasion (P = 0.01). Patients with STAS had significantly shorter recurrence‐free survival (RFS) and overall survival (OS) than those without STAS (P < 0.01 and P = 0.02, respectively). According to multivariate analysis, positivity for STAS was an independent prognostic parameter for RFS (P < 0.01), but not OS (P = 0.45). Three patients who developed surgical margin recurrence and one patient who developed distant recurrence were all positive for STAS.

STAS was predictive of poor postoperative survival in patients with early‐stage adenocarcinomas treated with limited resection and was associated with surgical margin recurrence.

• Early-stage
• limited resection
• lung adenocarcinoma
• spread through air spaces
• surgical margin recurrence

• Lung adenocarcinoma
• Lymph node metastasis
• Prognosis
• Spread through air spaces
• Surgery

• Metastasectomy
• Segmentectomy
• Wedge resection

• Spread through air spaces (STAS)
• lung cancer
• metastasis
• prognosis
• recurrence

• adenocarcinoma
• desquamative
• intra-alveolar
• pulmonary

• Lung
• Radio-resistant histology
• SBRT

• Adult
• Aged
• Aged, 80 and over
• Disease-Free Survival
• Female
• Humans
• Kaplan-Meier Estimate
• Lung Neoplasms/mortality
• Lung Neoplasms/radiotherapy
• Lung Neoplasms/secondary
• Male
• Middle Aged
• Neoplasm Metastasis/radiotherapy
• Radiation Tolerance
• Radiosurgery
• Retrospective Studies
• Young Adult

• Invasion
• Lung adenocarcinoma
• Recurrence
• Tumor spread through air spaces

• Colorectal cancer
• Gastrointestinal cancer
• Oligometastasis
• Stereotactic ablative body radiotherapy
• Stereotactic body radiation therapy, SBRT

• Colorectal cancer
• Pulmonary metastases
• Recurrent lung metastases
• Repeat metastasectomy

• Colorectal Neoplasms/pathology
• Female
• Humans
• Lung Neoplasms/mortality
• Lung Neoplasms/secondary
• Lung Neoplasms/surgery
• Male
• Metastasectomy
• Middle Aged
• Neoplasm Recurrence, Local/diagnosis
• Neoplasm Recurrence, Local/epidemiology
• Neoplasm Recurrence, Local/surgery
• Pneumonectomy
• Prevalence
• Reoperation
• Retrospective Studies
• Risk Factors
• Survival Rate

• Lung cancer
• Lung cancer surgery
• Lung pathology