Dual Image Navigation to Secure Surgical Margins in Thoracoscopic Segmentectomy.

PURPOSE: Video-assisted thoracoscopic surgery (VATS) segmentectomy is being increasingly used for the management of non-small cell lung cancer. For non-palpable lesions, surgeons frequently find difficulty in ensuring a sufficient surgical resection margin. OBJECTIVE: The purpose of this study was to evaluate the role of intraoperative dual image navigation in combination with the infrared thoracoscopy with intravenous injection of indocyanine green (IRT-ICG) method and intraoperative computed tomography (CT) in detecting oncological margins. METHODS: This study involved 34 consecutive patients who underwent both IRT-ICG and intraoperative CT-assisted thoracoscopic segmentectomy between October 2017 and July 2021. The intersegmental line on the visceral pleura was visualized using the IRT-ICG method. The intersegmental line was marked by clipping, and an intraoperative CT scan was performed under bilateral lung ventilation. Intraoperative CT or three-dimensional CT reconstruction images were used by surgeons to confirm the correct anatomic segmental border and to secure a sufficient resection margin. RESULTS: A well-defined intersegmental line was observed in 91.2% of patients. In eight cases, the surgeon needed to make some modifications to the resection line to secure a sufficient surgical margin. The mean surgical margin assessed on gross examination by the pathologist was 23.4 ± 9.0 mm. Complete resection was achieved in all patients using this approach. CONCLUSIONS: Intraoperative dual image navigation combined with the IRT-ICG method and intraoperative CT scan enables surgeons to perform definitive VATS segmentectomy for non-palpable lesions.

[Mixed Squamous Cell and Glandular Papilloma in the Peripheral Lung:Report of a Case].

Pulmonary papillary tumors are usually occur in the upper respiratory tract, and solitary papilloma in the peripheral lung are extremely rare. Lung papillomas sometimes show the elevation of tumor marker or F18-fluorodeoxyglucose (FDG) uptake, and are difficult to distinguish from lung carcinoma. Here we report a case of mixed squamous cell and glandular papilloma in the peripheral lung. An 85-years-old man without smoking history had been presented with an 8-mm nodule in right lower lobe in chest computed tomographic (CT) 2 years before. Since the diameter of the nodule increased to 12 mm, and positron emission tomography (PET) revealed an abnormally increased FDG uptake in the mass (SUVmax 4.61). StageIA2 lung cancer (cT1bN0M0) was suspected and wedge resection of the lung to make a definitive diagnosis and for treatment was performed. The definite pathological diagnosis was mixed squamous cell and glandular papilloma.

Regeneration of emphysematous lungs using gelatin sheets that release basic fibroblast growth factor.

PURPOSE: Basic fibroblast growth factor (bFGF) induces regeneration and neovascularization of the lungs. We conducted this study to demonstrate the regeneration of emphysematous lungs achieved by gelatin sheets that slowly release bFGF into the visceral pleura in a canine model. METHODS: Porcine pancreatic elastase was used to induce bilateral lower lobe pulmonary emphysema in dogs. Slow-release bFGF gelatin sheets were attached to the visceral pleura of the left lower lobe via thoracotomy. The subjects were divided into two groups: one treated with gelatin sheets containing slow-release bFGF (bFGF+ group, n = 5), and the other, treated with only gelatin sheets (bFGF- group, n = 5). The subjects were euthanized after 28 days and histologic lung assessment was performed. The results were evaluated in terms of the mean linear intercept (MLI) and microvessel count. RESULTS: The MLI was significantly shorter in the bFGF+ group than in the bFGF- group; (110.0 ± 24.38 vs. 208.9 ± 33.08 µm; P = 0.0006). The microvessel count was not significantly different between the bFGF+ and bFGF- groups (12.20 ± 3.007 vs. 5.35 ± 2.3425; P = 0.075); however, it was significantly higher in the bFGF-attached lungs than in the emphysema group (12.20 ± 3.007 vs. 4.57 ± 0.8896; P = 0.012). CONCLUSIONS: Attaching gelatin sheets with slow-release bFGF to the visceral pleura induced lung regeneration and vascularization in a canine pulmonary emphysema model.

Safe pneumonectomy for locally advanced lung cancer after induction therapy.

PURPOSE: To assess the safety and long-term outcomes of pneumonectomy after IT (IT-Pn) versus upfront pneumonectomy without IT (U-Pn) for locally advanced non-small-cell lung cancer (NSCLC). METHODS: We reviewed the clinical records of 69 patients who underwent pneumonectomy as U-Pn (n = 30) or IT-Pn (n = 39) between 2000 and 2019 at our institution, RESULTS: U-Pn included patients with pathological N0 (n = 13), N1 (n = 11) and N2 (n = 6). Among the patients treated with IT-Pn, 18 had pathological N0 (including 7 with complete responses), 5 had N1, 14 had N2, and 2 had N3. It was suggested that 22 cases could be down-staged after IT. The 5-year overall survival (OS) was 28.1% in the U-Pn group and 43.1% in the IT-Pn group (p = 0.275), being 40.2% for IT-Pn with p-N2,3, but not reached for U-Pn with N2 (p = 0.307). The 90-day mortality was 6.7% for the U-Pn group and 5.1% for the IT-Pn group (p = 0.646). Major complications occurred in 25 patients (64.1%) treated with IT-Pn and 18 patients treated with U-Pn (60.0%; p = 0.602). CONCLUSIONS: Pneumonectomy for NSCLC can be performed safely after IT with favorable results. For patients with N2 disease, induction therapy followed by surgery may warrant further study.

[Surgical Approach for Treatment of Postoperative Bronchopleural Fistula and Pyothorax].

A bronchopleural fistula is a serious condition that can develop into pyothorax. The incidence of bronchopleural fistula depends on the surgical procedure. Bronchopleural fistulas are classified into early and late types based on the time of development following surgical intervention. Early-stage fistulas show poor prognosis and require prompt treatment. It is important to confirm the status of infection in the thoracic cavity to devise an optimal treatment plan. Bronchopleural fistula closure is challenging and may be unsuccessful in patients with uncontrolled infection. Immediate open window thoracostomy should be performed in patients with empyema. The window is closed after effective clearance of thoracic cavity infection. Prompt and systematic treatment improves prognosis.

[Anomalous V2 Preoperatively Identified by Three-dimensional Computed Tomography in a Patient with Primary Lung Cancer of Right Upper Lobe].

A 61-year-old woman was found to have multiple ground-glass nodules( GGNs) in both lungs by chest computed tomography (CT) scan. The lesion of the right S2 contained a partial solid component and was suspected to be minimally invasive adenocarcinoma. Three-dimensional CT showed two anomalous V2s descending dorsally to the intermediate bronchus and draining into the inferior pulmonary vein. Thoracoscopic segmentectomy of the right S2 was performed safely. The pathological diagnosis was adenocarcinoma in situ. Since aberrant pulmonary vessels increases the surgical risk during video-assisted thoracoscopic anatomical lung resection, preoperative three-dimensional CT is useful in performing safe surgical procedure.

Eicosapentaenoic acid ameliorates pulmonary hypertension via inhibition of tyrosine kinase Fyn.

Pulmonary arterial hypertension (PAH) is a multifactorial disease characterized by pulmonary arterial vasoconstriction and remodeling. Src family tyrosine kinases, including Fyn, play critical roles in vascular remodeling via the inhibition of STAT3 signaling. EPA is known to inhibit Fyn kinase activity. This study investigated the therapeutic potential and underlying mechanisms of EPA and its metabolite, resolvin E1 (RvE1), to treat PAH using monocrotaline-induced PAH model rats (MCT-PAH), human pulmonary artery endothelial cells (HPAECs), and human pulmonary artery smooth muscle cells (HPASMCs). Administration of EPA 1 and 2 weeks after MCT injection both ameliorated right ventricular hypertrophy, remodeling and dysfunction, and medial wall thickening of the pulmonary arteries and prolonged survival in MCT-PAH rats. EPA attenuated the enhanced contractile response to 5-hydroxytryptamine in isolated pulmonary arteries of MCT-PAH rats. Mechanistically, the treatment with EPA and RvE1 or the introduction of dominant-negative Fyn prevented TGF-ß2-induced endothelial-to-mesenchymal transition and IL-6-induced phosphorylation of STAT3 in cultured HPAECs. EPA and RvE1 suppressed Src family kinases' activity as evaluated by their phosphorylation status in cultured HPAECs and HPASMCs. EPA and RvE1 suppressed vasocontraction of rat and human PA. Furthermore, EPA and RvE1 inhibited the enhanced proliferation and activity of Src family kinases in HPASMCs derived from patients with idiopathic PAH. EPA ameliorated PAH's pathophysiology by mitigating vascular remodeling and vasoconstriction, probably inhibiting Src family kinases, especially Fyn. Thus, EPA is considered a potent therapeutic agent for the treatment of PAH.

Current status of surgery for clinical stage IA lung cancer in Japan: analysis of the national clinical database.

PURPOSE: As the number of cases of early lung cancer in Japan grows, an analysis of the present status of surgical treatments for clinical stage IA lung cancer using a nationwide database with web-based data entry is warranted. METHODS: The operative and perioperative data from 47,921 patients who underwent surgery for clinical stage IA lung cancer in 2014 and 2015 were obtained from the National Clinical Database (NCD) of Japan. Clinicopathological characteristics, surgical procedure, mortality, and morbidity were analyzed, and thoracotomy and video-assisted thoracic surgery (VATS) were compared. RESULTS: The patients comprised 27,208 men (56.8%) and 20,713 women (43.2%); mean age, 69.3 years. Lobectomy was performed in 64.8%, segmentectomy in 15.2%, and wedge resection in 19.8%. The surgical procedures were thoracotomy in 12,194 patients (25.4%) and a minimally invasive approach (MIA) in 35,727 patients (74.6%). MIA was divided into VATS + mini-thoracotomy (n = 13,422, 28.0%) and complete VATS (n = 22,305, 46.5%). The overall postoperative mortality rate was 0.4%, being significantly lower in the MIA group than in the thoracotomy group (0.3% vs 0.8%, P < 0.001). CONCLUSIONS: Our analysis of data from the NCD indicates that MIA has become the new standard treatment for clinical stage IA lung cancer.

[Perioperative Management for Lung Cancer in the Elderly Over 75 Years Old].

In Japan, where the population is aging, the number of elderly lung cancer cases is expected to increase. Therefore, we retrospectively compared and examined about elderly lung cancer. METHOD: There were 1,283 patients undergoing surgery for lung cancer between 2009 and 2018 at our institution. We classified them into 75~85 years old, 85 years old or older, and younger than 75 years, and examined the patient background, surgical procedure, and perioperative complications. RESULT: 96.2% of 75~85 years group and 100% of 85 years old or older group had some history. There was a significant difference between the ages of 85 years old or older in PS 1 and above. There was a significant difference in limited resection between the 2 elderly groups compared to younger than 75 years group. The perioperative complication rates were 75~85 years old group (23.2%), 85 years old or older (30.9%), and younger than 75 years group (23.2%), with no significant difference. There were significant differences in postoperative delirium and chronic respiratory failure in 75~85 years group and 85 years old or older compared with younger than 75 years group. We performed a multivariate analysis of risk factors for complications. Males, PS 1 or higher, approach[ thoracotomy, video-assisted thoracic surgery (VATS)], and limited resection were considered to be independent factors. The 5-year survival rate was 70.9% in 75~85 years group, 39.3% in 85 years old or older group, and 81.0% in younger than 75 years group, and was significantly lower in 85 years old or older group. CONCLUSION: Elderly patients need to be aware of postoperative delirium and chronic respiratory failure. It is possible that the complication rate can be reduced by performing a thorough evaluation of operative resistance and selecting an appropriate surgical procedure in the elderly.

[Empyema Secondary to Percutaneous Liver Drainage via Thoracic Cavity for Hepatic Abscess].

Percutaneous liver drainage is associated with few complications. We report a case of empyema secondary to passage of a drain through the chest cavity in a patient treated with percutaneous liver drainage for hepatic abscess. A 72-year-old man was diagnosed with a liver abscess and underwent percutaneous liver drainage via the 7th intercostal space. He developed fever 7 days after the drainage procedure and was diagnosed with empyema on chest computed tomography and underwent video-assisted thoracoscopic curettage. Intraoperatively, we observed the liver drainage tube penetrated the thoracic cavity and the diaphragm, and he was diagnosed with iatrogenic empyema. The patient's postoperative course was uneventful, and the chest drain was removed on the 3rd postoperative day. Percutaneous liver drainage is associated with the risk of penetration of the thoracic cavity and the diaphragm.

High-Pressure Carbon Monoxide and Oxygen Mixture is Effective for Lung Preservation.

(1) Background: Heme oxygenase-1 (HO-1) degrades heme and generates carbon monoxide (CO), producing various anti-inflammatory, anti-oxidative, and anti-apoptotic effects. This study aimed to confirm the effects of CO on the ischemia-reperfusion injury (IRI) of donor lungs using a high-pressure gas (HPG) preservation method. (2) Methods: Donor rat and canine lungs were preserved in a chamber filled with CO (1.5 atm) and oxygen (O2; 2 atm) and were ventilated with either CO and O2 mixture (CO/O2 group) or air (air group) immediately before storage. Rat lungs were subjected to heterotopic cervical transplantation and evaluated after reperfusion, whereas canine lungs were subjected to allogeneic transplantation and evaluated. (3) Results: Alveolar hemorrhage in the CO/O2 group was significantly milder than that in the air group. mRNA expression levels of HO-1 remained unchanged in both the groups; however, inflammatory mediator levels were significantly lower in the CO/O2 group than in the air group. The oxygenation of graft lungs was comparable between the two groups, but lactic acid level tended to be higher in the air group. (4) Conclusions: The HO-1/CO system in the HPG preservation method is effective in suppressing IRI and preserving donor lungs.

[Intraoperative Navigation System during Thoracoscopic Segmentectomy for Non-palpable Pulmonary Tumors;Infrared Thoracoscopy (IRT)-Indocyanine Green (ICG) and Intraoperative Computed Tomography(CT)-assisted Method].

OBJECTIVES: Recently, the use of video-assisted thoracoscopic surgery (VATS) segmentectomy for pulmonary malignancies has increased. For non-palpable lesions, securing a sufficient surgical margin is more likely to be uncertain. The purpose of this study was to evaluate the usefulness of our intraoperative navigation system in combination with the infrared thoracoscopy (IRT)-indocyanine green (ICG) method and intraoperative computed tomography (CT) during VATS segmentectomy for non-palpable pulmonary malignancies. METHODS: This study involved 12 consecutive patients who underwent both IRT-ICG and intraoperative CT-assisted thoracoscopic segmentectomy. Identification of the intersegmental line on the visceral pleura was visualized using IRT-ICG. The intersegmental line was marked by clipping, and intraoperative CT scan was performed under bilateral lung ventilation. The intraoperative CT images were used by the surgeons to confirm the correct anatomic segmental border and to secure a sufficient resection margin. RESULTS: A well-defined intersegmental line was observed in 83.3% of the patients. The rate of concordance between 3-dimensional (3D)-CT images reconstructed from intraoperative CT and preoperative simulation 3D-CT imaging was 91.7%. The mean surgical margin assessed on gross examination by the pathologist was 22.3 ± 4.5 mm. Complete resection was achieved in all patients using this approach. CONCLUSIONS: Imaging support including preoperative simulation, IRT-ICG and intraoperative CT enables surgeons to perform definitive VATS segmentectomy for non-palpable lesions.

[Efficacy of TS-1 as a Late-Line Treatment for Metastatic Breast Cancer].

We report 4 female patients with metastatic breast cancer who were administered TS-1 as a late-line treatment and showed favorable outcomes. Their average age was 66.3. The patients, all of whom had undergone prior treatment with both anthracyclines and taxanes, showed intrinsic Luminal A or B subtypes. After administration of TS-1 in the lines of 2 to 9 in metastatic settings, all patients showed a long progression-free survival with a favorable quality of life.

Hypertension and Proteinuria as Predictive Factors of Effects of Bevacizumab on Advanced Breast Cancer in Japan.

Bevacizumab (BV), an inhibitor of vascular endothelial growth factor, is used in combination with paclitaxel (PTX) to treat advanced breast cancer. Hypertension and proteinuria are characteristic adverse events of BV therapy. We assessed the potential of these adverse events as predictors of BV treatment responses. Our results revealed that groups that developed hypertension and proteinuria early (by day 56) had a stronger antitumor response (Fisher's exact test p<0.05). However, no significant difference was observed in progression-free survival (the Kaplan-Meier method and Log-rank test). As a reference, age, the treatment line, subtypes, liver and renal function, diabetes mellitus and hyperlipidemia history, body mass index, influencing concomitant medicine, average relative dose intensity and hematotoxicity did not significantly differ between groups with or without hypertension and with or without proteinuria. These results indicate the potential of the development of hypertension and proteinuria as predictors of improved outcomes with PTX plus BV therapy in patients with breast cancer. However, since both adverse events may preclude the continuation of treatment, their earlier management may be required.

[Tracheal Injury Successfully Treated without Surgery;Report of a Case].

A 73-year-old man was injured after crashing his automobile into a concrete wall, and was admitted to our hospital with breathing difficulties. Chest computed tomography showed extensive mediastinal emphysema, right traumatic pneumothorax, and a suspected tracheal injury at the membranous region. Because of the associated tracheomalacia, the site of the tracheal injury was difficult to find by bronchoscopy. In addition, as the patient's respiratory condition was stable, surgical treatment was not chosen. Due to the continuous air leakage from the right lung, the patient underwent surgery after mediastinal and subcutaneous emphysema improved. The postoperative course was uneventful.

[Utility of Prophylactic Administration of Pegfilgrastim in Breast Cancer Chemotherapy].

Febrile neutropenia(FN)is a frequent adverse event observed in cancer patients undergoing chemotherapy that may cause life-threatening infections. However, reducing the dose of anti-cancer drugs for breast cancer in adjuvant settings to prevent FN has been reported to adversely affect patient survival. Therefore, it is important to administer therapeutic agents as per their prescheduled regimens without delays or reductions in the dosage. From April 2015 to September 2017, pegfilgrastim was administered to 24 patients with breast cancer(primary prevention in 11 patients and secondary prevention in 13 patients)to prevent FN during chemotherapy in either adjuvant or metastatic settings. We were able to reduce the incidence of FN through prophylactic administration of pegfilgrastim without encountering serious adverse events. The inclusion of pegfilgrastim is considered essential for the safe administration of chemotherapy according to a preplanned schedule. Here, we discuss the indications, efficacy, and safety of the drug.

[Surgical Resection of T4 Category Lung Cancer].

Surgery still remains the main stream in the multimodality treatment for locally advanced lung cancer. On the other hand, more than 50% of non-small cell lung cancer are excluded for surgical indications, especially T4 category of lung cancer. In this study, we showed 5 year overall survival rate of both 50 clinical T4 cases and 30 pathological T4 cases are 35.6% and 41.9% respectively. Those could be compared with the non-surgical treatment results in the literature. Through this study and analysis of other reports, we might consider surgical indications for T4 category lung cancer are as follows;invasion to mediastinum, spine, trachea, carina and additional nodules in ipsilateral different lobes with N0-1 status(esophagus is not included in this study). For obtaining R0 resection to improve survival and reducing postoperative morbidity and mortality rate, prudent evaluations for patients' selection including pre-operative staging before surgery are mandatory.

Relationship between dose-volume parameters and pulmonary complications after neoadjuvant chemoradiotherapy followed by surgery for lung cancer.

PURPOSE: This study evaluated the relationship between dose-volume histogram (DVH) parameters and pulmonary complications after neoadjuvant chemoradiotherapy (NACRT) followed by surgery for lung cancer. We also examined a new DVH parameter, because the unresected lung should be more spared than the later resected lung. PATIENTS AND METHODS: Data from 43 non-small cell lung cancer patients were retrospectively analyzed. The DVH parameters of the lung were calculated from the total bilateral lung volume minus (1) the gross tumor volume (DVHg) or (2) the later resected lung volume (DVHr). Radiation pneumonitis (RP) and fistula, including bronchopleural and pulmonary fistula, were graded as the pulmonary complications. Factors affecting the incidences of grade 2 or higher RP (≥G2 RP) and fistula were analyzed. RESULTS: Sixteen patients (37 %) experienced ≥G2 RP and a V20 value of the total lung minus the later resected lung (V20r) ≥ 12 % was a significant factor affecting the incidence of ≥G2 RP (p = 0.032). Six patients (14 %) developed a fistula and a V35 value of the total lung minus the gross tumor (V35g) ≥ 19 % and a V40g ≥ 16 % were significant factors affecting the incidence of fistula (p = 0.002 and 0.009, respectively). CONCLUSION: These DVH parameters may be related to the incidences of ≥G2 RP and fistula.

[Video-assisted Thoracoscopic Segmentectomy Using Infrared Thoracoscopy with Indocyanine Green].

The maintenance of a good surgical view is mandatory in video-assisted thoracoscopic surgery (VATS). For routine segmentectomy, it is necessary to re-inflate the lung in order to identify the intersegmental borders. However, such re-inflation can occasionally obstruct the surgical view and can lead to prolongation of operation time, particularly in the context of VATS. Infrared thoracoscopy( IRT) with indocyanine green (ICG) is a new method of evaluating lung perfusion. There are 2 methods in IRT. One is based on ICG absorption, and the other is based on ICG fluorescence. In our experience, both of them were useful for identification of segmental borders. However, the former method was superior for the clarity of images. No complications attributable to IRT with ICG were observed. IRT with ICG is based on blood flow rather than on ventilation and can thus achieve anatomical segmentectomy without lung re-inflation. This method will be especially useful for VATS segmentectomy.