Pulmonary metastases from pancreatic cancer have different clinico-radiological features compared with those from colorectal cancer.

BACKGROUND: Although pulmonary metastasectomy is a commonly-performed procedure, data are lacking on the feasibility and oncological efficacy of removal of pulmonary metastases from pancreatic cancer. In this study, we retrospectively compared features of pulmonary metastases from pancreatic cancer versus colorectal cancer (CRC, patients with CRC being common candidates for pulmonary metastasectomy) and outcomes of removing such metastases, with our aim being to identify specific features of the former. METHODS: Data on removal of 182 pulmonary metastases (29 from pancreatic and 153 from CRC) performed from January 2013 to April 2024 were included in this analysis. Radio-pathological findings were compared between these groups. The study cohort comprised 139 pulmonary metastasectomies in 119 patients (24 with pancreatic cancer and 95 with CRC) in whom R0 resection was achieved and follow-up data were available. RESULTS: Atypical radiological findings of pulmonary metastases, including polygonal-shape (P < 0.001), spiculae (P < 0.001), air bronchogram (P = 0.012), peripheral ground-glass opacities (P < 0.001), and pleural tags (P < 0.001) were present more frequently in metastases from pancreatic cancer than from CRC. Furthermore, pleural lavage cytology was more frequently positive in pulmonary metastases from pancreatic cancer than in those from CRC (P < 0.001). Disease-free survival was significantly shorter after the removal of metastases from pancreatic than from CRC (P < 0.001). CONCLUSIONS: Some pulmonary metastases from pancreatic cancer have atypical radiological features. Surgical interventions for these may enable diagnosis. The prognosis is significantly poorer after removing metastases from pancreatic cancer than from CRC. The therapeutic significance of our findings requires further investigation.

Angiopoietin-like 4 Is a Critical Regulator of Fibroblasts during Pulmonary Fibrosis Development.

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, and irreversible interstitial pneumonia caused by the excessive production and deposition of extracellular matrix components, including type I collagen. Activated fibroblasts, called α-SMA (α-smooth muscle actin)-expressing myofibroblasts, are the major source of type I collagen in pulmonary fibrosis (PF), but the mechanisms underlying disease progression have not been fully elucidated. Here, we obtained lung fibroblasts from patients with IPF from both nonfibrotic and fibrotic areas as determined by a lung computed tomography scan and compared gene expression between these areas by DNA microarray. We found that ANGPTL4 (angiopoietin-like 4) was highly expressed only in fibroblasts from the fibrotic area. ANGPTL4 was selectively expressed in the fibroblastic area of IPF lungs, where the myofibroblast marker α-SMA was also expressed. ANGPTL4 also regulates the gene expression of fibrosis-related markers, cell migration, and proliferation. In addition, ANGPTL4 expression in a murine model of PF induced by treatment with bleomycin was significantly induced in the lungs from the acute to the chronic phase. Single-cell transcriptome analysis during the course of bleomycin-induced PF revealed that Angptl4 was predominantly expressed in the activated fibroblasts and myofibroblasts. Moreover, the administration of recombinant ANGPTL4 to the bleomycin-induced fibrosis model significantly increased collagen deposition and exacerbated the PF. In contrast, the pathogenesis of PF in Angptl4-deficient mice was improved. These results indicate that ANGPTL4 is critical for the progression of PF and might be an early diagnostic marker and therapeutic target for IPF.

Outcome of Resected Lung Cancers with Subcentimeter Solid Component on Computed Tomography.

BACKGROUND: Although the opportunity to treat subcentimeter lung cancers has increased, the optimal surgical methods remain unclear. We performed a retrospective study to examine the clinical outcome of subcentimeter lung cancers. PATIENTS AND METHODS: In total, 118 patients who underwent curative resection for subcentimeter lung cancer from January 2005 to December 2013 were analyzed. Multivariate Cox proportional hazards models were used to calculate the hazard ratio to identify independent predictors of recurrence-free survival (RFS) and overall survival (OS). RESULTS: Anatomical resections were performed for 64 patients (59 lobectomies and 5 segmentectomies) and wedge resections for 54 patients. Recurrence developed in six patients who had consolidation-predominant tumors (consolidation/tumor [C/T] ratio of >0.5) and underwent wedge resections. The first recurrence patterns were regional recurrences in three patients, both regional and distant in one, and distant in two. Seventeen patients died of other causes. The multivariate analysis revealed that the C/T ratio was the independent predictor of RFS (p = 0.008) and OS (p = 0.011). CONCLUSION: Patients with subcentimeter lung cancer rarely developed recurrence. The C/T ratio was the independent prognostic factor, and all relapsed patients received wedge resections. Even for subcentimeter lung cancers, we should select the extent of pulmonary resection after thoroughly considering whether wedge resection (less invasiveness) is a reasonable alternative to anatomical resection (superior oncologic efficacy) considering the C/T ratio of the lesion.

Identification of fusion transcripts in sarcoma from archival formalin-fixed paraffin-embedded tissues: A next-generation sequencing approach.

Most sarcomas are highly aggressive, and cause necrosis and hemorrhage. The diagnosis of sarcoma is challenging because of the lack of specificity of immunohistochemical staining; however, molecular biological approaches, such as genetic mutation, chromosomal translocation, and gene amplification, are promising. In this study, we extracted RNA from formalin-fixed paraffin-embedded (FFPE) tissue derived from surgically resected specimens of sarcoma stored for various periods and performed next-generation sequencing (NGS) analysis by MiniSeq using the Archer Fusion-Plex Sarcoma Panel. RNA was extracted from 63 FFPE tissue samples, and the degree of RNA degradation was assessed. The number of reads and fragment lengths were evaluated by NGS analysis. RNA extraction and cDNA synthesis were successful in 56 cases and library preparation was possible. Fusion genes were detected in 16 of 63 archived FFPE tissue samples in this study. However, in 18 cases, fragmentation was strong, and high-quality libraries could not be obtained. Nevertheless, comprehensive analysis of fusion genes with high sequence specificity by NGS can be a powerful alternative to reverse transcription-polymerase chain reaction and fluorescence in situ hybridization methods.

Surgical treatment for secondary spontaneous pneumothorax: a risk factor analysis.

PURPOSE: While surgery is an effective treatment for secondary spontaneous pneumothorax (SSP), it can be difficult, because affected patients are usually in a poor general condition. The present study investigated the risk factors of postoperative complications after surgery for SSP. METHODS: Eighty-eight patients with SSP who underwent surgery from January 2006 to March 2018 were investigated. Clinical data were reviewed, and a multivariate analysis was performed. RESULTS: Eighty-four patients (95%) were males, and the median patient age was 72 years. Underlying lung diseases were chronic obstructive pulmonary disease in 58 patients (65.9%), interstitial pneumonia in 26 (29.5%), and others in 4 (4.5%). Postoperative complications developed in 21 patients (24%). Hospital mortality/prolonged length of stay occurred in 6 patients (7%). A multivariate analysis showed that the preoperative performance status (performance status 0-2 vs. 3, hazard ratio: 6.570, 95% confidence interval: 1.980-21.800) was an independent predictor of postoperative complications. CONCLUSION: Surgery for SSP contributed to early chest tube removal and favorable outcomes. However, rare fatal events occurred, and the patient performance status was a risk factor for postoperative complications. A careful evaluation of each patient's performance status is needed to determine the need for surgical intervention for SSP.

Isolation and culture of pleural mesothelial cells.

Purpose: Although the isolation of rat and mouse mesothelial cells has previously been reported, most mesothelial cells used for experimental studies are obtained from peritoneal cells. Here, we describe an optimized method for the isolation and in vitro propagation of rodent pleural mesothelial cells without the requirement for specialized surgical techniques. Materials and Methods: To harvest pleural mesothelial cells, the pleural space of 8-9-week-old rats or older mice was filled with 0.25% trypsin in ethylenediaminetetraacetic acid (EDTA) buffer for 20 min at 37 °C. Cells were then harvested, and incubated at 37 °C in a humidified atmosphere with 5% CO2. Immunofluorescence analysis of plated pleural mesothelial cells was performed using Alexa 546 (calretinin). To investigate optimal proliferation conditions, medium enriched with various concentrations of fetal calf serum (FCS) was used for pleural mesothelial cell proliferation. Results: By day 10, confluent cell cultures were established, and the cells displayed an obvious cobblestone morphology. Immunofluorescence analysis of the cells demonstrated that all stained positive for Alexa 546 (calretinin) expression. Mesothelial cells grew better in medium containing 20% FCS than with 10% FCS. Conclusions: This is a simple procedure for the efficient collection of primary pleural mesothelial cells, which were obtained in defined culture conditions from the euthanized rodent thoracic cavity using trypsin-EDTA treatment. The ability to easily culture and maintain identifiable pleural mesothelial cells from rodents will be helpful for future experiments using these cells.

Prognostic impact of underlying lung disease in pulmonary wedge resection for lung cancer.

BACKGROUND: Pulmonary wedge resection is an option for lung cancer patients with limited cardiopulmonary preservation. As the impact of underlying lung status on the prognosis of such patients remains unclear, we assessed this issue. METHODS: A total of 149 borderline surgical candidates with localized lung cancer who had undergone wedge resection were retrospectively investigated. Clinical variables related to perioperative morbidity, local control rate, and oncological outcomes based on underlying lung disease were analyzed. RESULTS: According to the risk analysis of postoperative complications, underlying lung disease did not influence the surgical morbidity. Postoperative recurrence occurred in 65 patients (locoregional recurrence in 36, distant metastasis in 12, and both simultaneously in 17). Multivariate analysis revealed that emphysema on computed tomography (CT) [hazard ratio (HR) 0.45; 95% confidence interval (CI) 0.21-0.99] was an independent indicator of locoregional recurrence. Forty-four patients died of lung cancer and 29 of other causes. Multivariate analysis demonstrated that interstitial lung disease on CT (HR 1.98; 95% CI 1.01-3.89) was a predictor of poor prognosis. CONCLUSION: Pulmonary wedge resection can be safely undergone by lung cancer patients regardless of pulmonary comorbidity, although underlying lung disease may influence the prognosis after wedge resection.

[Preoperative Detection of Pleural Adhesions Using Transthoracic Ultrasonography].

Recently, there has been an increase in the experience of lung surgery in cases with a history of thoracotomy or pneumonia. In these cases, pleural adhesion is often seen and makes the surgery to be difficult. Especially in thoracoscopic surgery, lung damage must be care at the 1st port insertion. In this report, the usefulness of the extent of pleural adhesion to the chest wall before surgery by using a transthoracic ultrasonography was assessed. Between April 2017 and September 2018, 32 patients underwent preoperative ultrasound examination, and 128 ports were evaluated whether had adhesions or not using lung sliding sign. All patients of 128, 24 adhesions were found at surgery, resulting in 14 true positive, 10 false negative, 0 false positive, and 104 true negative findings [sensitivity:58.3% (14/24), specificity: 100.0% (104/104), accuracy:92.2% (118/128)]. Especially, about the 1st port, accuracy was 93.8 % (30/32). In Conclusion, preoperative transthoracic ultrasonography could provide useful information on the pleural adhesion leading safe initial thoracoscopic access without lung injury.

Atrial natriuretic peptide prevents cancer metastasis through vascular endothelial cells.

Most patients suffering from cancer die of metastatic disease. Surgical removal of solid tumors is performed as an initial attempt to cure patients; however, surgery is often accompanied with trauma, which can promote early recurrence by provoking detachment of tumor cells into the blood stream or inducing systemic inflammation or both. We have previously reported that administration of atrial natriuretic peptide (ANP) during the perioperative period reduces inflammatory response and has a prophylactic effect on postoperative cardiopulmonary complications in lung cancer surgery. Here we demonstrate that cancer recurrence after curative surgery was significantly lower in ANP-treated patients than in control patients (surgery alone). ANP is known to bind specifically to NPR1 [also called guanylyl cyclase-A (GC-A) receptor]. In mouse models, we found that metastasis of GC-A-nonexpressing tumor cells (i.e., B16 mouse melanoma cells) to the lung was increased in vascular endothelium-specific GC-A knockout mice and decreased in vascular endothelium-specific GC-A transgenic mice compared with control mice. We examined the effect of ANP on tumor metastasis in mice treated with lipopolysaccharide, which mimics systemic inflammation induced by surgical stress. ANP inhibited the adhesion of cancer cells to pulmonary arterial and micro-vascular endothelial cells by suppressing the E-selectin expression that is promoted by inflammation. These results suggest that ANP prevents cancer metastasis by inhibiting the adhesion of tumor cells to inflamed endothelial cells.

Validating margin status in lung wedge resection for clinical stage I non-small cell lung cancer.

Stage I non-small cell lung cancer (NSCLC) is a localized disease without metastasis; therefore, it can be treated effectively with local therapies. Pulmonary resection is the most frequent treatment, performed as pulmonary wedge resection, segmentectomy, lobectomy, or pneumonectomy. Some retrospective clinical studies of pulmonary wedge resection suggest that its outcome may be inferior to that of anatomical pulmonary resection, whereas other recent studies, which assess surgical margin status, leveled acceptable outcomes. Since the outcome of pulmonary wedge resection for lung cancer may depend on tumor size, distance from the surgical margin to the tumor, tumor size/margin distance ratio, and margin cytology results, a prospective study assessing these parameters is ongoing. This will allow us to identify the clinical implications of these factors and predict which patients are likely to have a good outcome.

Prognostic Analysis of Surgical Resection for Pulmonary Metastasis from Hepatocellular Carcinoma.

INTRODUCTION: Pulmonary metastases are the most common among extrahepatic recurrences from hepatocellular carcinoma (HCC). It causes high risk of HCC-related death, despite recent progress in therapeutic options. However, a role of pulmonary metastasectomy as well as prognostic factors after metastasectomy has not been well established. We aimed to investigate survival outcomes and prognostic factors after pulmonary resection for metastases from HCC. METHODS: A series of 93 patients who underwent pulmonary resections for metastases from HCC between June 1990 and July 2013 from multi-institutional database were retrospectively evaluated. Perioperative clinicopathological data and their association with prognosis were investigated. RESULTS: Of 93 patients, 77 had one pulmonary metastasis, and 16 had two or more. Recurrence after pulmonary resection was noted in 60 patients (64.5 %). The estimated 5-year overall survival rate was 41.4 % with median survival time after pulmonary metastatectomy of 39.0 months. Univariate prognostic analysis showed that disease-free interval of ≥12 months was significantly associated with favorable outcomes in both overall survival (5-year rate, 59.3 vs. 28.7 %, p = 0.026) and disease-specific survival (5-year rate, 62.5 vs. 36.2 %; p = 0.038) after pulmonary metastatectomy. A multivariate analysis revealed that disease-free interval was an independent prognostic factor (HR = 2.020, 95 % CI, 1.069-3.816, p = 0.030). CONCLUSION: We have shown that a disease-free interval was an independent prognostic factor in patients who underwent pulmonary resection for metastasis from HCC. Also, pulmonary metastasectomy can be one of the therapeutic choices for select patients.

Perioperative circulating tumor cells in surgical patients with non-small cell lung cancer: does surgical manipulation dislodge cancer cells thus allowing them to pass into the peripheral blood?

PURPOSE: We herein evaluated the status of circulating tumor cells (CTC) dislodged from the tumor during surgery in patients who underwent pulmonary resection for non-small cell lung cancer (NSCLC) to assess the clinical implications. METHODS: Tumor cells in the peripheral arterial blood before surgery (Before) and immediately after lung resection (After) and in the blood from the pulmonary vein of the resected lung were detected using a size selective method. The clinicopathological characteristics and the prognosis were then analyzed according to the CTC status: no tumor cells detected (N), single tumor cell or total number less than 4 cells (S), and existence of clustered cells (C). RESULTS: According to the CTC status, the patients were classified into the following three groups: Before-C and After-C, Group I (n = 6); Before-S or N and After-C, Group II (n = 9); and Before-S or N and After-S or N, Group III (n = 8). Group III showed a high rate of p-stage IA, smaller tumor size, lower CEA level, lower SUVmax level, and a higher relapse-free survival rate than the other groups. CONCLUSIONS: CTCs were detected in patients after undergoing lung resection, some of which may have been dislodged by the surgical procedure. The presence of clustered CTCs after the operation indicated an unfavorable outcome.

[Lung Excision for Clinical Stage I Lung Cancer].

A strategy of indicating lung excision for high risk patients is discussed based on reviewing of treatments for clinical stage I lung cancer. According to clinical studies of lung excision or stereotactic body radiation therapy both results may be similar, while a multicenter randomized prospective study is on-going. Since the result of lung excision may be revealed to depend on tumor size, tumor location in the lung, distance from surgical margin to tumor, tumor size-margin distance ratio and margin cytology results, a prospective study is recommended, which will be able to assessed clinical implications of such factors to extract patients having good prognoses.

Impact of cardiopulmonary complications of lung cancer surgery on long-term outcomes.

PURPOSE: The impact of postoperative cardiopulmonary complications on long-term outcomes has not been established. We investigated the effects of acute postoperative cardiopulmonary complications not only on cancer recurrence, but also on cardiovascular or respiratory events in the chronic phase after lung cancer surgery. METHODS: From a prospective single-institution database of 496 consecutive patients, who underwent lung cancer surgery between August, 2008 and December, 2011, medical records, including information about cardiovascular or respiratory events and cancer recurrence in the chronic phase (>6 months) after surgery, were analyzed retrospectively. Results were compared between patients with vs. those without postoperative cardiopulmonary complications in the acute phase. RESULTS: Postoperative cardiopulmonary complications were identified in 90 (20%) patients. There were significantly more cardiovascular or respiratory events in the chronic phase after lung cancer surgery in the patients who had suffered postoperative cardiopulmonary complications in the acute phase than in those who had not (23 vs. 5%; p < 0.0001). CONCLUSIONS: Postoperative cardiopulmonary complications in the acute phase were associated with a higher incidence of cardiovascular or respiratory events in the chronic phase after lung cancer surgery. CLINICAL TRIAL REGISTRATION NUMBER: JPRN-UMIN2370.

[Additional Lobectomy after Pulmonary Excision for Non-invasive Lung Adenocarcinoma due to Malignant Positive Cytology at the Residual Lube].

A 67-year-old male was pointed out a pure ground grass opacity sized 1.7 cm in computed tomography (CT), which reminded unchanged size in CT findings for 18 months. This region was removed using pulmonary wedge resection with margin length of 0.5 cm and clustered pulmonary adenocarcinoma cells were revealed by cytological examination at the margin of the residual lung, thus additional left upper lobectomy was performed later.

Atrial natriuretic peptide inhibits lipopolysaccharide-induced acute lung injury.

OBJECTIVES: We recently reported that administration of atrial natriuretic peptide during the perioperative period has prophylactic effects with respect to not only cardiovascular but also respiratory complications following pulmonary resection. However, its mechanisms are not well understood. The objective of the present study was to investigate the mechanism of the prophylactic effects of atrial natriuretic peptide in an acute lung injury model. METHODS: For the evaluation of the early phase of pulmonary inflammation, in vitro and in vivo studies using lipopolysaccharide were used. In the in vitro study, the effects of atrial natriuretic peptide on the induction of E-selectin by lipopolysaccharide in human pulmonary artery endothelial cells were evaluated. In the in vivo study, the effects of atrial natriuretic peptide on lipopolysaccharide-induced inflammatory cell infiltration and cytokine levels including tumor necrosis factor-alpha and interleukin-6 in the bronchoalveolar lavage fluid in the lungs of C57/B6 mice were examined. The number of myeloperoxidase-positive staining cells in the tissue sections of the lung of lipopolysaccharide-administered C57/B6 mice was also evaluated. RESULTS: Atrial natriuretic peptide significantly attenuated the up-regulation of E-selectin expression induced by lipopolysaccharide in human pulmonary artery endothelial cells. There were significantly lower cell counts and levels of tumor necrosis factor-alpha and interleukin-6 in the bronchoalveolar lavage fluid of atrial natriuretic peptide-treated mice compared to control mice after lipopolysaccharide injection. In addition, there were significantly fewer myeloperoxidase-positive cells in atrial natriuretic peptide-treated mice than in control mice after lipopolysaccharide injection. CONCLUSIONS: Atrial natriuretic peptide had a protective effect in the lipopolysaccharide-induced acute lung injury model. Atrial natriuretic peptide may be of value in therapeutic strategies aimed at the treatment of acute lung injury such as pneumonia or acute respiratory distress syndrome.

Feasibility of aspirin continuation during the perioperative period for pulmonary resection in lung cancer patients: a retrospective study at a single institute in Japan.

PURPOSE: To evaluate the feasibility of aspirin continuation during the perioperative period for pulmonary resection in lung cancer patients. METHODS: A retrospective study was conducted in 46 patients who were taking aspirin and underwent pulmonary resection. The indications for aspirin were generally a cardiovascular or cerebrovascular comorbidity. Whether to continue or discontinue aspirin was determined based on the severity of the cardiovascular or cerebrovascular comorbidity, along with the patient's overall condition. The intraoperative and postoperative outcomes were compared between patients continuing and those discontinuing aspirin. RESULTS: Twenty patients continued (group C) and 26 patients discontinued (group D) aspirin. The length of the operation (226 ± 97 min in group C vs. 189 ± 90 min in group D), intraoperative bleeding (234 ± 232 vs. 204 ± 367 g) and average pleural discharge on postoperative days 1, 2 and 3 (331, 230 and 215 vs. 304, 210 and 174 ml/day) showed no significant differences between the two groups. The postoperative complication rates were also not significantly different between the two groups [eight patients (40%) in group C vs. nine patients (35%) in group D]. CONCLUSIONS: Continuous administration of aspirin during the perioperative period for pulmonary resection in lung cancer patients appears to be clinically feasible in the Japanese population.

Inhaled tiotropium to prevent postoperative cardiopulmonary complications in patients with newly diagnosed chronic obstructive pulmonary disease requiring lung cancer surgery.

PURPOSE: A new diagnosis of chronic obstructive pulmonary disease is often made during the evaluation of patients requiring lung cancer surgery. The objective of the present study was to evaluate the clinical effects of inhaled tiotropium on the postoperative cardiopulmonary complications in patients with untreated chronic obstructive pulmonary disease requiring lung cancer surgery. METHODS: A retrospective study involving 104 consecutive patients with moderate to severe chronic obstructive pulmonary disease who underwent a lobectomy for lung cancer at two specialized thoracic centers between April 2008 and October 2011 was performed. The results were compared between patients who did and did not receive inhaled tiotropium during the perioperative period. The primary endpoint was the incidence of postoperative cardiopulmonary complications. The postoperative white blood cell counts and C-reactive protein levels as biomarkers of inflammation were also examined. RESULTS: The incidence of postoperative cardiopulmonary complications was significantly lower in the tiotropium group than in the control group (18 vs. 48 %, P = 0.001). Patients in the tiotropium group also showed significantly lower white blood cell counts and C-reactive protein levels postoperatively. CONCLUSIONS: Inhaled tiotropium treatment during the perioperative period had a prophylactic effect on postoperative cardiopulmonary complications in patients with newly diagnosed chronic obstructive pulmonary disease requiring lung cancer surgery.

Surgery for pulmonary malignancies in patients with a previous history of head and neck squamous cell carcinoma.

PURPOSE: To examine the perioperative and long-term outcomes of surgery for malignancies of the lungs in patients with a history of head and neck squamous cell carcinoma (HNSCC) and to evaluate the risk factors associated with postoperative complications. METHODS: The data of 39 patients with a history of HNSCC who underwent pulmonary resection were reviewed. The perioperative and long-term outcomes were analyzed. RESULTS: Eight patients (21%) had difficult airways, and nine patients (23%) developed postoperative complications. A low body mass index (<18.5), a history of malignancy besides HNSCC and chronic obstructive pulmonary disease were each found to be significantly associated with the development of postoperative complications. The 5-year survival rate of all patients was 80%. CONCLUSIONS: The airway management of patients with a history of HNSCC should be carefully undertaken. Preoperative assessment of their nutritional status and careful prevention of air leakage during surgery are important. Because favorable outcomes can be achieved, aggressive surgical management should be considered for the treatment of pulmonary malignancies in patients with a history of HNSCC.