Diagnostic method of mass spectrometry for detecting lymph node metastasis of non-small cell lung cancer.

BACKGROUND: Histopathology by pathologists is essential in the diagnosis of non-small cell lung cancer (NSCLC). However, auxiliary diagnostic procedures for malignant tumor have continued to evolve. Despite the poor prognosis of patients with NSCLC, the application of the latest procedures and technologies to the field of lung cancer has lagged. Mass spectrometry was used to detect trace amounts of peptides in human tissue with high accuracy. The aim of this study was to establish a method for diagnostic mass spectrometry to identify lymph node metastasis by detecting cytokeratin (CK)19, a useful biomarker in lung cancer. METHODS: We collected 81 lymph nodes with positive expression of CK19 in patients who underwent radical surgical resection in the Department of Thoracic Surgery at Iwate Medical University between May 2020 and December 2022. An X500R instrument was used for sample analysis. A positive result for lymph node metastasis as the detection at least two product ions (FGPGVAFR and ILGATIENSR) from CK19 was defined. RESULTS: Our study indicated a high diagnostic efficiency for mass spectrometry, with 87.5% sensitivity and 91.2% specificity. The mutual concordance of mass spectrometry methods and histopathological diagnosis was 90.1%. CONCLUSIONS: Mass spectrometry offers high diagnostic accuracy and can be clinically applied to auxiliary diagnostic procedures for lymph node metastasis from NSCLC.

Characteristics and prognostic analysis of patients with detected KRAS mutations in resected lung adenocarcinomas by peptide nucleic acid-locked nucleic acid polymerase chain reaction (PNA-LNA PCR) clamp method.

Background: Kirsten rat sarcoma virus (KRAS) gene mutations are a type of driver mutation discovered in the 1980s, but for a long time no molecular targeted drugs were available for them. Recently, sotorasib was developed as a molecular targeted drug for KRAS mutations. It is therefore necessary to identify the characteristics of patients with KRAS mutations. Methods: This was the single-institution retrospective study. Surgically resected tumors from lung adenocarcinoma patients were collected at a single institution from June 2016 to September 2019. Peptide nucleic acid-locked nucleic acid polymerase chain reaction (PNA-LNA PCR) clamp analysis of KRAS G12X mutations was compared with analysis by therascreen KRAS RGQ kit. The association between KRAS mutation status and patient characteristics and prognosis was assessed. Results: Among 499 lung adenocarcinomas, KRAS mutations were evaluated in 197 cases, excluding stage IV lung cancer and tumors with epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) mutations. KRAS G12X mutations were detected in 59 cases (29.9%). The highest frequency by gene mutation subtype was G12V in 23 cases (39.0%), followed by G12C in 16 cases (27.1%), G12D in 12 cases (20.3%), G12S in 4 cases (6.8%) and G12A in 2 cases. For the G12C mutation, the PNA-LNA PCR clamp and therascreen methods were consistent, but for the G12D and G12S mutations, the PNA-LNA PCR clamp method showed higher detection rates. In operable tumors, G12C mutations were more frequent in males, smokers, and patients with high expression of programmed death-ligand 1 (PD-L1), and had no correlation with prognosis. Conclusions: By the PNA-LNA PCR clamp method, G12C mutation of surgical specimens was detected successfully. The PNA-LNA PCR clamp method is expected to be applied to the detection of druggable G12C mutations.

Prognostic Impact of Tumor-Associated Macrophage-Related Markers in Patients with Adenocarcinoma of the Lung.

BACKGROUND: Macrophage polarization is an important pathogenetic factor in neoplastic diseases. Phosphorylated signal transducer and activator of transcription 1 (phospho-STAT1) regulates the M1 phenotype, and c-Maf regulates the M2 phenotype. However, the role of macrophage phenotype in lung adenocarcinoma (LAD) remains unclear. PATIENTS AND METHODS: We examined whether the density of M1 and M2 macrophages was associated with prognosis in patients with LAD using double-labeling immunohistochemistry. In addition, programmed death ligand 1 (PD-L1) expression was investigated. Immune cells coexpressing CD68 and phospho-STAT1 were considered M1 macrophages, whereas those coexpressing CD68 and c-Maf were recognized as M2 macrophages. Patients with LAD (N = 307) were divided into two cohorts (n = 100 and n = 207) to evaluate the associations of M1 and M2 phenotypes with prognosis in patients with LAD. We determined the cut-off values of CD68/phospho-STAT1-positive cells and CD68/c-Maf-positive cells to assess correlations with overall survival (OS) using receiver operating characteristic curve analysis in the first cohort. RESULTS: According to the cut-off values of 5 or less CD68/phospho-STAT1-positive cells and more than 11 CD68/c-Maf-positive cells, high expression of CD68/c-Maf and low expression of CD68/Phospho-STAT1 were identified as independent prognostic markers for OS and disease-free survival (DFS). Moreover, the M1/M2 ratio (0.19 or less) was a poor prognostic factor for OS and DFS. However, PD-L1 expression did not correlate with patient outcomes. CONCLUSIONS: Overall, these findings suggest that double immunostaining of markers of phospho-STAT1 (M1) and c-Maf (M2) can be used as prognostic indicators for patients with LAD.

Optimal period of smoking cessation to reduce the incidence of postoperative pulmonary complications in lung cancer.

OBJECTIVES: Postoperative pulmonary complications (PPCs) provoke an extended hospital stay and increased postoperative mortality. Although several factors can cause PPCs, smoking is the only factor that can be adjusted within a short period of time preoperatively. However, the optimal period of smoking cessation to reduce the risk of PPCs remains unclear. METHODS: A total of 1260 patients with primary lung cancer who underwent radical pulmonary resection between January 2010 and December 2021 were analysed retrospectively. RESULTS: We classified patients into 2 groups: non-smokers (patients who had never smoked) and smokers (patients who had ever smoked). The frequency of PPCs was 3.3% in non-smokers and 9.7% in smokers. PPCs were significantly less frequent in non-smokers than in smokers (P < 0.001). When smokers were classified according to the duration of smoking cessation, the frequency of PPCs was significantly lower for a duration of 6 weeks or more than for <6 weeks (P < 0.001). In a propensity score analysis performed for 6 or >6 and <6 weeks' smoking cessation in smokers, the frequency of PPCs was significantly lower for smokers with 6 or more weeks' smoking cessation than for smokers with <6 weeks' smoking cessation (P = 0.002). A multivariable analysis identified <6 weeks' smoking cessation as a significant predictor of PPCs for smokers (odds ratio: 4.55, P < 0.001). CONCLUSIONS: Smoking cessation for 6 or more weeks preoperatively significantly reduced the frequency of PPCs.

Surgical treatment for lung metastasis of inflammatory myofibroblastic tumor of the lung: A case report.

Inflammatory myofibroblastic tumor (IMT) is a rare disease that is considered an intermediate neoplasm, with the risk of recurrence and metastasis. Surgical treatment is the standard therapy for IMT, although there are only a few reports of surgery for lung metastasis of pulmonary IMT. We opine that surgical treatment might be effective not only for localized tumors, but also for cases of lung metastasis of IMT.

Prognostic and predictive value of CD163 expression and the CD163/CD68 expression ratio for response to adjuvant chemotherapy in patients with surgically resected lung squamous cell carcinoma.

BACKGROUND: Macrophages infiltrating the tumor microenvironment are defined as tumor-associated macrophages (TAMs). TAMs can be polarized into different phenotypes, that is, proinflammatory M1 macrophages or anti-inflammatory M2 macrophages. Particularly, M2 macrophages promote angiogenesis, wound healing, and tumor growth. This study aimed to evaluate whether M2 TAMs can serve as a useful marker to predict prognosis and benefit from adjuvant chemotherapy in patients with surgically resected lung squamous cell carcinomas (SCCs). METHODS: We examined 104 patients with SCC. Tissue microarrays were constructed, and the density of TAMs was analyzed by immunohistochemistry for expression of CD68 and CD163. The relationship between CD68 and CD163 expression and the CD163/CD68 expression rate and clinicopathological characteristics including patient outcomes were investigated. In addition, propensity score matching (PSM) analysis was conducted to test the hypothesis that these cells significantly influenced chemotherapy responses. RESULTS: Univariate analysis revealed that pathological stage, CD163 expression, and the CD163/CD68 expression ratio were significant prognostic factors. Multivariate analysis showed that these factors were all independent prognostic factors. Thirty-four pairs were determined by using PSM analysis. Patients with a low CD163/CD68 expression ratio benefited more from adjuvant chemotherapy than those with a high ratio. CONCLUSION: We suggest that M2 TAMs may be a useful marker to predict prognosis and differential benefit from adjuvant chemotherapy in patients with surgically resected lung SCCs.

Outcomes and pulmonary function after sleeve lobectomy compared with pneumonectomy in patients with non-small cell lung cancer.

BACKGROUND: Sleeve lobectomy is recommended to avoid pneumonectomy and preserve pulmonary function in patients with central lung cancer. However, the relationship between postoperative pulmonary functional loss and resected lung parenchyma volume has not been fully characterized. The aim of this study was to evaluate the relationship between pulmonary function and lung volume in patients undergoing sleeve lobectomy or pneumonectomy. METHODS: A total of 61 lung cancer patients who had undergone pneumonectomy or sleeve lobectomy were analyzed retrospectively. Among them, 20 patients performed pulmonary function tests, including vital capacity (VC) and forced expiratory volume in 1 s (FEV1) tests, preoperatively and then about 6 months after surgery. VC and FEV1 ratios were calculated (measured postoperative respiratory function/predicted postoperative respiratory function) as the standardized pulmonary functional loss ratio. RESULTS: Thirty-day operation-related mortality was significantly lower after sleeve lobectomy (3.2%) than pneumonectomy (9.6%). The 5-year relapse-free survival rate was 46.67% versus 29.03%, and the 5-year overall survival rate was 63.33% versus 38.71% in patients receiving sleeve lobectomy versus pneumonectomy. The VC ratio in the pneumonectomy group was better than in the sleeve lobectomy group (1.003 ± 0.117 vs. 0.779 ± 0.12; p = 0.0008), as was the FEV1 ratio (1.132 ± 0.226 vs. 0.851 ± 0.063; p = 0.0038). CONCLUSIONS: Both short-term and long-term outcomes were better with sleeve lobectomy than pneumonectomy. However, actual postoperative pulmonary function after pneumonectomy may be better than clinicians expect, and pneumonectomy should still be considered a treatment option for patients with sufficient pulmonary reserve and in whom sleeve lobectomy is less likely to be curative.

Inferior pulmonary ligament division during left upper lobectomy causes pulmonary dysfunction.

OBJECTIVES: The division of inferior pulmonary ligament (IPL) during upper lobectomy (UL) was believed to be mandatory to dilate the remaining lung sufficiently. However, the benefits, especially postoperative pulmonary function, remain controversial. This study aimed to evaluate whether IPL division leads to pulmonary dysfunction. METHODS: This retrospective study included 213 patients who underwent UL between 2005 and 2018. They were categorized into an IPL division group (D group, n = 106) and a preservation group (P group, n = 107). Postoperative dead space at the lung apex, pulmonary function and complications were assessed using chest X-rays and spirometry. Changes in bronchial angle, cross-sectional area and circumference of the narrowed bronchus on the excised side were measured on three-dimensional computed tomography. RESULTS: There was no significant difference in the postoperative complication rate, the dead space area, forced vital capacity (FVC), or forced expiratory volume in 1 s (FEV1) between the 2 groups after right UL (FVC; P = 0.838, FEV1; P = 0.693). By contrast, after left UL pulmonary function was significantly better in the P than in the D group (FVC; P = 0.038, FEV1; P = 0.027). Changes in bronchial angle did not significantly differ between the 2 groups. The narrowed bronchus's cross-sectional area (P = 0.021) and circumference (P = 0.009) were significantly smaller in the D group than in the P group after left UL. CONCLUSIONS: IPL division during left UL caused postoperative pulmonary dysfunction and airflow limitation due to bronchial kinking. IPL preservation may have a beneficial impact on postoperative pulmonary function.

Assessment of lymph node metastasis of ≤20 mm non-small cell lung cancer originating from superior segment compared to basal segment.

BACKGROUND: Segmentectomy with curative intention is occasionally performed for early non-small cell lung cancer (NSCLC). However, a major problem has been pointed out, in that the rate of locoregional recurrence is higher after segmentectomy than after lobectomy. This study aimed to investigate differences in rates of lymph node metastasis between segment 6 and basal segment NSCLC as potential candidates for segmentectomy and to explore factors associated with locoregional recurrence of segmentectomy. METHODS: We retrospectively analyzed 461 patients with lower lobe NSCLC who underwent segmentectomy or lobectomy with mediastinal lymph node dissection between 2011 and 2021. Among these, 122 patients with clinical N0 NSCLC, diameter ≤ 20 mm, and consolidation tumor ratio >0.5 were analyzed. RESULTS: The 122 patients were divided into a segment 6 group (n = 51) and a basal segment group (n = 71). Frequency of lymph node metastasis was significantly higher in the segment 6 group (17.7%) than in the basal segment group (4.2%; p = 0.01). Metastases to lymph node station 7 were seen in five of 122 patients (4.1%). Hilar lymph node metastasis occurred in nine of 122 patients (7.4%). Notably, metastases to station 11, 11i and 11 s lymph nodes were the most frequent patterns for hilar lymph nodes (41.7%). CONCLUSIONS: Station 11 lymph nodes are adjacent to the remaining lung segment or pulmonary artery in S6 segmentectomy or basal segmentectomy. Part of the NSCLC in segment 6 patients may thus be considered for lobectomy owing to the difficulty of complete dissection of station 11 lymph nodes.

Prognostic impact of tumor microenvironment-related markers in patients with adenocarcinoma of the lung.

Cancer-associated fibroblasts (CAFs) are a prominent component in the tumor microenvironment (TME), which plays an important role in lung carcinogenesis. Here, we investigated microenvironmental markers expressed by CAFs, including α-smooth muscle actin, CD10, podoplanin, fibroblast-specific protein 1, platelet-derived growth factor α and ß, fibroblast-associated protein, tenascin-C, zinc finger E-box binding homeobox 1 (ZEB1), and twist-related protein 1 expression levels. We evaluated samples from 257 patients with lung adenocarcinoma (LAD) to assess the associations of CAF-related protein expression patterns with prognosis. LAD cases were stratified using cluster analysis. To determine the utility of prognostic markers in LAD, univariate and multivariate analyses were performed. LAD cases were classified into subgroups 1 and 2. Subgroup 2 was shown to be significantly correlated with disease-free and overall survival using univariate and multivariate analyses in this group. Upregulation of podoplanin was identified as a single prognostic marker in this study by univariate and multivariate analyses. In addition, ZEB1 overexpression was correlated with disease-free survival. Our current results suggested that the specific CAF phenotype (e.g., the expression pattern of CAF-related proteins) could predict outcomes in patients with LAD. In addition, podoplanin upregulation may predict outcomes in these patients.

Intraoperative rapid immunohistochemistry with noncontact antibody mixing for undiagnosed pulmonary tumors.

Knowledge of the histologic type and primary origin of pulmonary tumors is essential when preparing a surgical strategy. Intraoperative diagnosis of hematoxylin and eosin (H&E)-stained frozen sections is the gold standard, but reliable pathology requires time-consuming immunohistochemistry (IHC) to distinguish among histological types/organ origins and to analyze molecular status. The aim of this study was to evaluate the clinical reliability of a new rapid-IHC technique for intraoperative diagnosis of pulmonary tumors. In total, 169 patients with undiagnosed pulmonary tumors were enrolled in a multicenter prospective observational study. At three institutes, pulmonary tumor samples were collected through core needle biopsy and/or surgery to determine surgical strategies. Using a new device for rapid IHC, we applied a high-voltage, low-frequency alternating current (AC) field, which mixes the available antibody as the voltage is switched on/off. Rapid IHC can provide tumor histologic type/origin diagnoses within 20 min, as opposed to the 3-6 h required for conventional IHC. No false diagnoses of malignancy were rendered in any of the cases when using simple H&E staining. With H&E staining alone, the overall definitive diagnosis rate, the rate of defined tumor origin, and the rate of determined histological type were 76.92%, 85.80%, and 90.53%, respectively. When rapid IHC was added, those rates were significantly improved to 88.76%, 94.67%, and 91.72%, respectively. By providing prompt and accurate intraoperative histological/molecular analysis, rapid IHC driven by AC mixing could serve as an effective clinical tool guiding the surgical strategy for undiagnosed pulmonary tumors.

The new IASLC grading system for invasive non-mucinous lung adenocarcinoma is a more useful indicator of patient survival compared with previous grading systems.

BACKGROUND: The International Association for the Study of Lung Cancer (IASLC) Pathology Committee recently proposed a new histological grading system for invasive lung adenocarcinoma (ADC). This study evaluated the usefulness of this grading system. METHODS: A total of 395 patients with ADC were examined. ADCs were reclassified based on comprehensive histological subtyping according to the IASLC grading system. We evaluated the following histological grading systems for invasive ADC: the architectural (Arch), Sica's grading, and IASLC grading systems. Multivariate analyses of overall and recurrence-free survival (RFS) based on these three grading systems were performed using Cox proportional hazards models. RESULTS: Multivariate analysis showed that all three grading systems were useful for predicting the outcomes of patients at all stages. However, the IASLC grading system was superior to the Arch and Sica's grading systems in differentiating grade 3 from grade 1 ADCs in terms of both overall survivals (IASLC vs. Arch vs. Sica's grading systems: hazard ratio [HR] = 3.77 vs. 3.03 vs. 2.63) and RFS (HR = 4.25 vs. 2.69 vs. 2.4). CONCLUSION: The newly proposed IASLC grading system was useful for predicting patient outcomes and was superior to the other grading systems in detecting high-grade malignancy.

Evaluation of pulmonary artery bleeding during thoracoscopic pulmonary resection for lung cancer.

BACKGROUND: Bleeding from the pulmonary artery (PA) can be fatal in video-assisted thoracoscopic surgery (VATS) for lung cancer. We evaluated intraoperative PA injury and assessed precautions for thoracoscopic anatomic pulmonary resection. METHODS: We retrospectively analyzed a total of 1098 patients who underwent radical surgery for lung cancer utilizing complete VATS from January 2010 to December 2021. RESULTS: A total of 16 patients (1.5%) had PA injury during VATS, while hemostasis was performed by conversion to thoracotomy in eight patients (50.0%). Although there was a significantly greater operation time and blood loss for patients in the PA injury group (318.4 vs. 264.9 min, p = 0.001; 550.3 vs. 60.5 g, p ≤ 0.001, respectively), there was no significant different for the chest tube insertion duration and length of postoperative hospital stay (4.9 vs. 7.8 days, p = 0.157; 10.6 vs. 9.9 days, p = 0.136, respectively). There was a significant difference observed for the surgical procedure related to the left upper lobectomy in the PA injury group (43.8 vs. 18.8%, p = 0.012), with the primary causative PA determined to be the left anterior segmental PA (A3 ) (31.3%). CONCLUSIONS: VATS is both feasible and safe for lung cancer treatment provided the surgeon performs appropriate hemostasis, although fatal vascular injury could potentially occur during VATS. Surgeons need to be aware of the pitfalls regarding PA dissection management.

High expression of fibroblast-activating protein is a prognostic marker in non-small cell lung carcinoma.

BACKGROUND: Fibroblast-activating protein (FAP) is expressed in cancer-associated fibroblasts (CAFs) in many human carcinomas and in some types of carcinoma cells. Here, we examined the proportion of FAP protein expression in non-small cell lung carcinoma (NSCLC) and investigated the correlation of FAP expression with clinicopathological background. METHODS: In total, 344 NSCLC tissues were examined. Tissue microarrays were constructed, and FAP expression was analyzed using immunohistochemistry. The status of FAP expression in tumor cells and CAFs was correlated with clinicopathological background, molecular features, and patient outcomes. RESULTS: A total of 280 patients (81.4%) had low FAP expression, and 64 patients (18.6%) had high FAP expression in tumor cells. In CAFs, 230 patients (66.9%) had low FAP expression, and 114 patients (33.1%) had high FAP expression. In multivariate analyses, high FAP expression in tumor cells was an independent predictive factor of both overall survival (OS; hazard ratio [HR] = 2.57, 95% confidence interval [CI]: 1.49-4.42, p < 0.001) and recurrence-free survival (RFS; HR = 2.13, 95% CI: 1.38-3.29, p < 0.001). Based on combinations of FAP expression in tumor cells and CAFs, patients with LowT /LowCAFs had better OS and RFS than did those in the other subgroups. By contrast, patients with HighT /HighCAFs had poor OS and RFS compared with those in the other subgroups. CONCLUSIONS: Overall, FAP expression in tumor cells and the combination FAP expression in tumor cells and CAFs were strongly associated with patient survival and may be useful predictive biomarkers for patient outcomes in NSCLC.

Correlation of tumor microenvironment-related markers with clinical outcomes in patients with squamous cell carcinoma of the lung.

Background: Squamous cell carcinoma (SCC) is the major histological type in lung cancer (LC). The tumor microenvironment (TME) drives tumor progression and metastasis. In the TME, cancer-associated fibroblasts (CAFs) play key roles in carcinogenesis. However, the roles of CAFs in lung SCC remain unknown. In this study, we evaluated whether the CAF phenotype was determined by various CAF-related proteins and whether CAF-related protein expression contributed to clinical outcomes in patients with lung SCC. Methods: We examined the associations of CAF- and epithelial-mesenchymal transition (EMT)-related markers expressed in CAFs, including α-smooth muscle actin (α-SMA), CD10, podoplanin, fibroblast-specific protein 1 (FSP1), platelet-derived growth factor receptor (PDGFR) α, PDGFRß, adipocyte enhancer-binding protein 1 (AEBP1), fibroblast activation protein (FAP), tenascin-C, Zinc finger E-box binding homeobox 1 (ZEB1), and twist homolog 1 gene (TWIST1), in 108 lung SCC tissues using immunohistochemistry. In addition, cluster analysis was used to identify objective expression patterns of immunohistochemical markers. Finally, the CD3/CD8 ratio was evaluated in order to identify the associations of CAF-related proteins with the CD3/CD8 ratio using immunohistochemistry. Results: SCC samples were classified into two subgroups (CAF-phenotype), which were significantly correlated with disease-free and overall survival using univariate and multivariate analyses. Moreover, high AEBP1 expression was identified as an independent prognostic marker in this cohort by univariate and multivariate analyses. The CD3/CD8 ratio was not correlated with the CAF-phenotype. Conclusions: The presence of a specific subgroup defined by multiple markers could be used for prediction of prognosis in patients with lung SCC. In addition, AEBP1 overexpression played key roles in prediction of a poor prognosis in patients with lung SCC.

No-drain management after thoracoscopic lung wedge resection with a novel intraoperative sealing test.

OBJECTIVE: Although previous studies have reported the safety of no-drain management after thoracoscopic wedge resection, most of those studies were non-inferiority trials. The aim of this study was to evaluate whether no-drain management with an optimal sealing test affects post-operative complications in patients after thoracoscopic wedge resection. METHODS: A total of 906 patients who underwent thoracoscopic lung wedge resection for various disorders except secondary pneumothorax between 2011 and 2020 were analyzed. According to intraoperative findings from the sealing test, patients were divided into groups with chest drain placement (Drain group, n = 514) or no-drain management (no-drain group, n = 392). Our intraoperative sealing test used a flexible drain (Blake®, 19-Fr; Ethicon, Somerville, NJ) connected to the chest drain bag (- 10 cmH2O) to monitor intrathoracic pressure and detect occult alveolar air leakage. Propensity score matching was conducted to balance baseline characteristics of the two groups and reduce selection bias. RESULTS: A total of 250 pairs were matched and standardized differences suggested proper matching had been achieved. Mean length of post-operative hospital stay (4.6 days vs. 3.2 days, p < 0.001) was significantly lower in the no-drain group. Total post-operative complication rates were significantly lower in the no-drain group (6.4% vs. 2.4%, p = 0.03). CONCLUSIONS: No-drain management after thoracoscopic wedge resection was associated with fewer post-operative complications and shorter hospital stay in selected patients. Our novel intraoperative sealing test may be useful for no-drain management of select patients.

[A Case of Laparoscopic Ileus Release for Intestinal Obstruction Due to Small Intestinal Metastasis Four Years after Penile Cancer Surgery].

We report a rare case of metastatic small intestine cancer originating from penile cancer triggered by intestinal obstruction, with some review of the literature. The case was a 78-year-old man at the first visit. Partial penile resection was performed for penile cancer. Histopathological findings were squamous cell carcinoma, and the surgical margin was negative. The stage at the time of the first surgery was T2N0M0, Stage Ⅱ. He came to the hospital with a complaint of abdominal pain 4 years after the operation. He was diagnosed with intestinal obstruction and was treated medically. He underwent medical treatment for 12 days, but did not improve, so he underwent laparoscopic ileus release. Surgical findings showed a neoplastic lesion in the abdominal cavity, and the site was obstructed, and partial resection of the small intestine including the neoplastic lesion was performed. Pathological examination revealed small intestinal metastasis of penile cancer. Postoperative intestinal obstruction improved and he was discharged without complications. After discharge, he underwent systemic chemotherapy at an outpatient clinic, but died of the primary disease 181 days after intestinal obstruction.

Stapler-lavage cytology using a new rapid immunocytochemistry for evaluating surgical margin status after pulmonary sublobar resection.

OBJECTIVE: Sublobar resection is considered the gold standard for selected patients with pulmonary metastasis or who are compromised in some way. However, an unfavorable outcome after sublobar resection is local/margin recurrence. The aim of this study was to evaluate the clinical reliability of a new rapid-stapler lavage immunocytochemistry (ICC) technique for assessing margin malignancy. The method uses non-contact alternating current (AC) mixing to achieve more stable staining. METHODS: Twenty-one patients who underwent sublobar resection, including 16 wedge resections, for pulmonary metastasis or lung cancer in a compromised host between September 2016 and December 2017 were retrospectively reviewed. All margin specimens were intraoperatively evaluated with HE staining of frozen sections and stapler lavage cytology using Papanicolaou staining and rapid-ICC. RESULTS: Rapid-stapler lavage ICC can be used to diagnose surgically safe margins within 20 min during sublobar resections. Although in all cases margins were diagnosed as cancer free based on HE staining of frozen sections, two of four patients diagnosed with malignant-positive margins based on rapid ICC experienced local/margin recurrence. CONCLUSIONS: Rapid-stapler lavage ICC with AC mixing could potentially serve as a clinical tool for prompt determination of margin malignant status after pulmonary sublobar resection.

Utility of mass spectrometry and artificial intelligence for differentiating primary lung adenocarcinoma and colorectal metastatic pulmonary tumor.

BACKGROUND: Rapid intraoperative diagnosis for unconfirmed pulmonary tumor is extremely important for determining the optimal surgical procedure (lobectomy or sublobar resection). Attempts to diagnose malignant tumors using mass spectrometry (MS) have recently been described. This study evaluated the usefulness of MS and artificial intelligence (AI) for differentiating primary lung adenocarcinoma (PLAC) and colorectal metastatic pulmonary tumor. METHODS: Pulmonary samples from 40 patients who underwent pulmonary resection for PLAC (20 tumors, 20 normal lungs) or pulmonary metastases originating from colorectal metastatic pulmonary tumor (CRMPT) (20 tumors, 20 normal lungs) were collected and analyzed retrospectively by probe electrospray ionization-MS. AI using random forest (RF) algorithms was employed to evaluate the accuracy of each combination. RESULTS: The accuracy of the machine learning algorithm applied using RF to distinguish malignant tumor (PLAC or CRMPT) from normal lung was 100%. The algorithms offered 97.2% accuracy in differentiating PLAC and CRMPT. CONCLUSIONS: MS combined with an AI system demonstrated high accuracy not only for differentiating cancer from normal tissue, but also for differentiating between PLAC and CRMPT with a short working time. This method shows potential for application as a support tool facilitating rapid intraoperative diagnosis to determine the surgical procedure for pulmonary resection.