En bloc resection of gastrobronchial fistula associated with mesh infection.

A 50-year-old woman presented with chief complaints of fever and cough. She had a poorly controlled left lung abscess and a history of congenital left diaphragmatic hernia treated 9 years prior with composite mesh. Computed tomography showed suspected fistula formation between the left lower lung lobe and stomach, and the tract was visualized in a contrast study from an upper gastrointestinal endoscope. We suspected a gastrobronchial fistula associated with mesh infection and performed en bloc resection of the mesh and inflamed organ tissue, comprising resection of the left lower lung lobe and left diaphragm, partial gastrectomy, and splenectomy. The diaphragm was reconstructed using the latissimus dorsi and rectus abdominis muscles. To our knowledge, this is the first report describing this treatment strategy for gastrobronchial fistula associated with mesh infection. The patient's postoperative course was favourable.

Dislocation of a middle lobe torsion-preventing bridging structure with an absorptive sheet and fibrin glue: a case report.

BACKGROUND: Middle lobe torsion is a rare complication of right upper lobectomy. Middle lobe torsion can be critical; thus, various preventive measures are used. CASE PRESENTATION: A 77-year-old man underwent thoracoscopic right upper lobectomy with partial middle resection and S6 segmentectomy for right upper lobe lung cancer located at the confluence of the three lobes and lower lobe lung cancer. Inversion of the middle lobe was observed during lung expansion before chest closure. A bridging structure with an absorptive sheet and fibrin glue was placed in the basal section of the middle lobe under lung expansion to prevent torsion. On postoperative day 1, the patient was tachycardic and was found to have decreased lung field permeability. The patient underwent emergency surgery for suspected middle lobe torsion. Dislocation of the bridging structure between the basal segments of the middle lobe was confirmed, and the middle lobe was deviated cephalad. In addition, pulmonary congestion in S4 due to pressure stenosis of V4 caused by the deviation of the middle lobe was observed, and middle lobe resection was performed. The postoperative course was uneventful. CONCLUSIONS: This case suggested that the reinforcement method with an absorptive sheet and fibrin glue lacked sufficient strength to prevent middle lobe torsion. Stronger fixation should be considered if the middle lobe rotation is thought to be sufficiently strong when the lung is reinflated before chest closure.

Serum immunogloblins might be useful predictors of immune-related adverse events after immune checkpoint inhibitor usage in lung cancer.

We herein report a 79-year-old woman who underwent surgery had recurred non-small cell lung cancer and developed irAEs following ICI treatment. During ICI treatment, we conducted monthly measurements of the serum antibody levels in this patient, including those which were both tumor- (anti-p53 antibody) and nonspecific (immunoglobulins). Anti-p53 antibodies and IgM had not increased during ICI treatment, but the serum levels of IgG and IgA had gradually increased before the occurrence of irAEs. These results suggest that monitoring serum immunoglobulin levels might enable the early detection of ICI-induced immune responses in patients with lung cancer.

Thickened parietal pleural covering in intractable pneumothorax: A case report.

Introduction and importance: Choosing the optimal surgical approach for intractable pneumothorax can be challenging for surgeons. Case presentation: A case describing the management of intractable pneumothorax has been presented. Clinical discussion: Resection is not suitable in a stiff lung from repeated pleurodesis, and multiple air leakage points would make it more intricate.The ideal alternative is the use of another material to cover the entire lesion. Conclusion: A thickened parietal pleura covering is an effective surgical approach for intractable pneumothorax.

CD155 expression and its clinical significance in non-small cell lung cancer.

CD155 serves an important role in tumor progression by promoting cell proliferation and migration. CD155 is also involved in the immune evasion of tumor cells, which may cause the development and progression of tumors. Accordingly, CD155 has emerged as a novel target in cancer immunotherapy; however, its expression in lung cancer remains unclear. To assess CD155 expression and its prognostic significance, 96 patients with completely resected pathologic stage I adenocarcinoma of the lung were retrospectively reviewed. Immunohistochemical staining was performed to evaluate CD155 expression on tumor cells. Expression levels of programmed death-ligand 1 (PD-L1), another molecule participating in immune evasion, were also evaluated immunohistochemically. CD155 expression was positive in 37 patients (38.5%). CD155-positivity was associated with aggressive tumor behavior, such as pleural invasion and vascular invasion. In addition, CD155-positivity was a significant factor to predict a poor prognosis (5-year overall survival (OS) rate, 63.3% for CD155-positive patients vs. 93.1% for CD155-negative patients; P<0.001). Patients harboring tumors with positive CD155 and PD-L1 expression showed the poorest prognosis (5-year OS rate, 44.4% for both-positive patients vs. 85.4% for the other patients; P<0.001). The positive expression status of both CD155 and PD-L1 was a significant and independent unfavorable prognostic factor (hazard ratio, 3.86; 95% confidence interval, 1.51-9.89; P=0.004; in a multivariate analysis). In conclusion, CD155-positivity was associated with aggressive tumor behavior, and was a factor to predict a poor prognosis. Its prognostic impact was enhanced when combined with PD-L1 expression status. These results should be validated in a large-scale study.

Surgical strategy for malignant pleural mesothelioma: the superiority of pleurectomy/decortication.

PURPOSE: Both extrapleural pneumonectomy (EPP) and pleurectomy/decortication (P/D) are used for the surgical treatment of malignant pleural mesothelioma (MPM). This study aimed to compare the operative and clinical outcomes and survival between EPP and P/D. METHODS: We performed a retrospective analysis of the surgical and clinical data of 40 patients who underwent either EPP (n = 18) or P/D (n = 22) for MPM at our institution between January 2000 and December 2018. RESULTS: In comparison to EPP, P/D was associated with a higher intraoperative bleeding volume (1175 vs 1805 ml, p = 0.0020) and greater duration of postoperative thoracic drainage (3 vs 16 days, p < 0.0001). Adjuvant chemotherapy was more common after P/D (81.8%) than after EPP (33.3%; p = 0.0024). For epithelioid-type MPM, overall survival (OS) and recurrence-free survival (RFS) were significantly better in patients who underwent P/D in comparison to those who underwent EPP (p = 0.040 and p = 0.015, respectively), with no difference for the biphasic and sarcomatoid types of MPM. A Cox proportional hazards regression model identified P/D as a significant favorable prognostic factor for OS [hazard ratio (HR), 0.391; 95% confidence interval (CI), 0.175-0.871; p = 0.022] and RFS (HR, 0.418; 95% CI, 0.190-0.920; p = 0.030). CONCLUSIONS: Based on our findings, P/D may be superior to EPP for improving the prognosis of patients with resectable epithelioid-type MPM.

Salvage surgery following immuno-chemo-radiotherapy for advanced non-small cell lung cancer.

BACKGROUND: Salvage surgery following definitive radiotherapy or systemic treatment has become a feasible treatment option in selected patients with advanced initially unresectable non-small cell lung cancer. Recent clinical trials of neoadjuvant treatment have showed that surgery following immuno-chemotherapy is safely performed. Here, we present the first case of salvage surgery following immuno-chemotherapy with concurrent definitive radiotherapy for advanced lung large cell carcinoma. CASE PRESENTATION: A 44-year male was admitted to our hospital for salvage surgery. Ten months prior to this administration, he had been diagnosed with unresectable large cell carcinoma with malignant pericardial effusion (clinical stage IVA/T3N2M1A; no driver-gene alteration) originating from the right upper lobe (RUL). Due to rapid intrabronchial tumor growth causing severe dyspnea, emergency bronchial stenting in the right main bronchus using an expandable metallic stent had been performed. Thereafter, he had received immuno-chemotherapy with concurrent definitive radiotherapy. Despite dramatic radiographic response, he had suffered from persistent and refractory Pseudomonas aeruginosa lung infection associated with bronchial stent placement. As pericardial effusion had disappeared and no distant metastasis had developed, he was diagnosed with a potentially curable disease and was referred to our hospital. An extended sleeve resection was successfully performed, and pathological sections revealed that pathologic complete response was achieved with immuno-chemo-radiotherapy. The patient received no subsequent treatment, and is alive without tumor recurrence at 8 months after surgery. CONCLUSIONS: Salvage surgery following immuno-chemotherapy with concurrent definitive radiotherapy for advanced non-small cell lung cancer may be feasible in selected patients, and may be considered as a treatment option to control local disease.

The role of virtual-assisted lung mapping 2.0 combining microcoils and dye marks in deep lung resection.

OBJECTIVES: Virtual-assisted lung mapping 2.0 is a novel preoperative bronchoscopic lung mapping technique combining the multiple dye marks of conventional virtual-assisted lung mapping with intrabronchial microcoils to navigate thoracoscopic deep lung resection. This study's purpose was to evaluate the feasibility of virtual-assisted lung mapping 2.0 in resecting deeply located pulmonary nodules with adequate margins. METHODS: A multicenter, prospective single-arm study was performed from 2019 to 2020 in 8 institutions. The selection criteria were barely identifiable nodules requiring sublobar lung resections, nodules requiring resection lines reaching the inner 2/3 of the pulmonary lobe on computed tomography images in wedge resection, or the nodule center located in the inner 2/3 of the pulmonary lobe in wedge resection or segmentectomy. Resection margins larger than 2 cm or the nodule diameter were considered successful resection. Bronchoscopic placement of multiple dye marks and microcoil(s) was conducted 0 to 2 days before surgery. RESULTS: We analyzed 65 lesions in 64 patients. The diameter and depth of the targeted nodules and the minimum required resection depth reported as median (interquartile range) were 9 (7-13) mm, 11 (5-15) mm, and 30 (25-35) mm, respectively. Among 60 wedge resections and 5 segmentectomies, successful resection was achieved in 64 of 65 resections (98.5%; 95% confidence interval, 91.7-100). Among 75 microcoils placed, 3 showed major displacement after bronchoscopic placement. There were no severe adverse events associated with the virtual-assisted lung mapping procedure. CONCLUSIONS: This study demonstrated that virtual-assisted lung mapping 2.0 can facilitate successful resections for deep pulmonary nodules, overcoming the limitations of conventional virtual-assisted lung mapping.

Virtual-assisted lung mapping in sublobar resection of small pulmonary nodules, long-term results.

OBJECTIVES: The short-term efficacy of virtual-assisted lung mapping (VAL-MAP), a preoperative bronchoscopic multi-spot lung-marking technique, has been confirmed in 2 prospective multicentre studies. The objectives of this study were to analyse the local recurrence and survival of patients enrolled in these studies, long-term. METHODS: Of the 663 patients enrolled in the 2 studies, 559 patients' follow-up data were collected. After excluding those who did not undergo VAL-MAP, whose resection was not for curative intent, who underwent concurrent resection without VAL-MAP, or who eventually underwent lobectomy instead of sublobar resection (i.e. wedge resection or segmentectomy), 422 patients were further analysed. RESULTS: Among 264 patients with primary lung cancer, the 5-year local recurrence-free rate was 98.4%, and the 5-year overall survival (OS) rate was 94.5%. Limited to stage IA2 or less (≤2 cm in diameter; n = 238, 90.1%), the 5-year local recurrence-free and OS rates were 98.7% and 94.8%, respectively. Among 102 patients with metastatic lung tumours, the 5-year local recurrence-free rate was 93.8% and the 5-year OS rate was 81.8%. Limited to the most common (colorectal) cancer (n = 53), the 5-year local recurrence-free and OS rates were 94.9% and 82.3%, respectively. CONCLUSIONS: VAL-MAP, which is beneficial in localizing small barely palpable pulmonary lesions and determining the appropriate resection lines, was associated with reasonable long-term outcomes. SUBJ COLLECTION: 152, 1542.

Lung Autotransplantation for Bulky Superior Sulcus Tumor With Hilar Involvement.

Lung autotransplantation with ex vivo bench surgery is a useful surgical technique for centrally located and locally advanced lung cancer to spare lung parenchyma by avoiding pneumonectomy. Here, we present a patient with a bulky superior sulcus tumor with hilar involvement for which lung-sparing complete resection was achieved with autotransplantation. After concurrent chemoradiotherapy, en bloc resection, consisting left pneumonectomy combined with apical chest wall resection (1-4 ribs), back-table extended double-sleeve resection after lung preservation, and reimplantation of basal segment was performed. The postoperative course was uneventful, and the patient is alive without tumor recurrence at 18 months after surgery.

Prognostic impact of circulating tumor cells detected with the microfluidic "universal CTC-chip" for primary lung cancer.

Detecting rare circulating tumor cells (CTCs) in the bloodstream is extremely challenging. We had previously developed a novel polymeric microfluidic device, "CTC-chip," for capturing CTCs and have shown high capture efficiency in lung cancer cell lines by conjugating Abs against epithelial cell adhesion molecules (EpCAM). This study aimed to optimize the EpCAM-chip and clarify the prognostic impact of CTCs in lung cancer patients. Of 123 patients with pathologically proven lung cancer, both progression-free survival (P = .037) and cancer-specific survival (P = .0041) were predominantly poor when CTCs were detected before treatment. After classification into surgical and chemotherapy groups, progression-free survival was worse in CTC-positive patients in both groups (surgery, P = .115; chemotherapy, P = .012), indicating that the detection of baseline CTCs is a risk factor for recurrence and progression. Furthermore, we recovered captured CTCs using micromanipulators and undertook mutation analysis using PCR. Thus, the EpCAM-chip is a highly sensitive system for detecting CTCs that contributes to the prediction of recurrence and progression and enables genetic analysis of captured CTCs, which could open new diagnostic, therapeutic, and prognostic options for lung cancer patients.

Relationship between anti-acetylcholine receptor antibodies and the development of post-thymectomy myasthenia gravis in patients with thymoma: a single-center experience.

BACKGROUND: Approximately 15-29.6% of patients with thymoma have myasthenia gravis (MG). Some of these patients develop MG after thymectomy despite having no history of MG or related symptoms. Few previous studies have examined the risk factors for the development of post-thymectomy MG in patients with thymoma. Herein, we retrospectively reviewed our institutional experience with patients with thymoma who developed MG after thymectomy. METHODS: Twenty-six patients with thymoma but without MG, who were tested preoperatively for anti-acetylcholine receptor antibody (anti-AChR-Ab) levels, underwent surgical resection at our hospital between 2013 and 2020. Patients with thymic carcinoma were excluded from the study. We evaluated the association of outcomes with preoperative anti-AChR-Ab levels and post-thymectomy MG. We performed a χ2 test for bivariate analysis of categorical data. Differences were considered significant at P<0.05. RESULTS: The characteristics of the 26 patients (median age: 62 years; 8 men, 18 women) were as follows: World Health Organization (WHO) classifications AB (n=8), B1 (n=9), B2 (n=6), B3 (n=1), and others (n=2) and Masaoka stage I (n=12), II (n=9), III (n=3), and IVa (n=2). Among the 26 patients, only five had high (>0.3 nmol/L) preoperative anti-AChR-Ab levels. Post-thymectomy MG occurred in two of the five patients (40%) with high preoperative anti-AChR-Ab levels. A high preoperative serum anti-AChR-Ab titer was significantly associated with post-thymectomy MG (P=0.0267). The anti-AChR-Ab titer was also measured postoperatively in four of the five (80%) patients with high preoperative levels. The anti-AChR-Ab titer decreased in two of these four patients, and neither developed postoperative MG. CONCLUSIONS: Preoperative and postoperative anti-AChR-Ab positivity might be associated with post-thymectomy MG. Therefore, regular measurement of anti-AChR-Ab levels after thymectomy is required.

Splenic infarction after left upper lobectomy: a report of a case.

We report the case of a 70-year-old man who developed a splenic infarction due to a thrombus in the pulmonary vein (PV) stump after left upper lobectomy (LUL). Preoperative imaging showed a mass measuring > 5 cm in the upper lobe of the left lung, and sputum cytology revealed squamous cell carcinoma. Therefore, video-assisted thoracoscopic LUL was performed. The postoperative course was uneventful but biochemical blood tests showed an increased inflammatory response. Contrast-enhanced computed tomography revealed splenic infarction and a thrombus in the left superior PV stump. Prompt treatment with anticoagulants was administered, and the patient was discharged with mild recovery. However, the patient developed cerebral infarction after discharge and died 33 days after the surgery. Splenic infarction is a rare postoperative complication, with only three reported cases, including this report. However, this condition should be considered along with PV thrombus when evaluating an increased inflammatory response after LUL.

Novel circulating tumor cell-detection chip combining conventional podoplanin and EGFR antibodies for all histological malignant pleural mesothelioma.

In our previous study, a microfluidic system was developed based on podoplanin detection for capturing circulating tumor cells (CTCs), derived from malignant pleural mesothelioma (MPM). However, non-epithelioid MPM shows low podoplanin protein expression compared with that in epithelioid MPM; thus, some CTC populations may be missed. To overcome this limitation, a new CTC-detection chip was developed by combining the conventional podoplanin antibody (clone: NZ-1.2) with an epidermal growth factor receptor (EGFR)-targeted antibody (cetuximab). The cell-capture efficiency of the Cocktail-chip reached 100% in all the histological MPM cell lines. The median CTC-counts from 19 patients with MPM (epithelioid/non-epithelioid: 10/9) with the NZ-1.2- and Cocktail-chips were 1 and 3 (P=0.311) in 1 ml peripheral blood, 1.5 and 2 (P=0.332) in epithelioid MPM, and 1 and 3 (P=0.106) in non-epithelioid MPM, respectively. Overall, the Cocktail-chip showed an improved ability to detect more CTCs in patients with non-epithelioid MPM compared with that in the conventional NZ-1.2-chip, showing non-significant, but higher CTC detection. Furthermore, CTC-counts, determined using the Cocktail-chip were significantly correlated with the clinical stage of non-epithelioid MPM. In epithelioid MPM, the Cocktail-chip achieved a CTC-detection efficiency equivalent to that in the conventional NZ-1.2-chip. The Cocktail-chip enabled sensitive CTC detection of all histological MPM, including the non-epithelioid subtype, which may provide a foundation for the diagnosis, treatment, and prognosis of MPM progression.

Non-incisional pleurectomy/decortication for malignant pleural mesothelioma.

OBJECTIVE: Pleurectomy/decortication has been preferably employed as a curative-intent surgery for malignant pleural mesothelioma. However, visceral pleurectomy during pleurectomy/decortication provides technical challenges. For visceral pleurectomy, pleural incisions are commonly made to create a dissection plane between the visceral pleura and the lung parenchyma, which may cause tumor dissemination and may not allow en bloc complete resection of the entire pleura. To overcome such potential disadvantages, we have developed a novel surgical technique without any pleural incision (non-incisional pleurectomy/decortication) to achieve en bloc removal of the entire pleura. METHODS: A total of 36 consecutive patients who underwent non-incisional pleurectomy/decortication for malignant pleural mesothelioma from January 2017 through December 2020 in our institute were retrospectively reviewed to assess the feasibility. RESULTS: Macroscopic complete resection was achieved in 31 patients (86.1%) with non-incisional pleurectomy/decortication. In the majority of patients (n = 29), en bloc complete resection of the entire pleura was achieved (without pleural laceration in 10 and with some pleural laceration in 19 patients). The total operation time and the duration of visceral pleurectomy were significantly shorter as compared with those for conventional pleurectomy/decortication (median, 350 versus 506 min [P = 0.011], and 43 versus 97 min [P < 0.001], respectively). Among 36 patients who underwent non-incisional pleurectomy/decortication, postoperative complications developed in 13 patients (36.1%), and one patient died on the postoperative day 95 caused by aggressive tumor progression of residual tumor. CONCLUSIONS: Non-incisional pleurectomy/decortication is a fast and feasible technique to achieve en bloc macroscopic complete resection for malignant pleural mesothelioma.

Rapid Progression of Liver Fibrosis Induced by Acute Liver Injury Due to Immune-related Adverse Events of Atezolizumab.

A 72-year-old woman with advanced lung cancer had received systemic chemotherapy including atezolizumab. About three months after the initial administration of atezolizumab, her liver enzyme levels increased. The histopathological findings of the initial liver biopsy revealed acute inflammatory infiltrate, predominantly CD3+, CD4+ and CD8+ T lymphocytes, in the hepatic lobules. We diagnosed her with atezolizumab-induced immune-related acute hepatitis. Oral corticosteroid therapy successfully improved the elevation of serum aminotransferases. A sequential liver biopsy demonstrated the rapid progression of liver fibrosis. Because hepatocellular carcinoma occurs most often in advanced cases of chronic liver disease, we should pay close attention to immune-related acute hepatic injury when treating patients with advanced liver diseases using atezolizumab.

The surgical technique for complete resection of lung cancer invading the intrapericardial pulmonary vein and left atrium.

In patients with lung cancer invading the left atrium, performing complete resection is difficult. In many cases of complete resection, pneumonectomy is performed. We herein report two techniques in which complete resection with negative margins at the intrapericardial pulmonary vein and left atrium was achieved without pneumonectomy. In the first technique, the groove of the pericardium between the right and left atrium was dissected and an atrial cuff was made in a manner that elongated the intrapericardial pulmonary vein. In the second technique, traction was applied to the atrial cuff, and only the middle lobe vein of the elongated pulmonary vein was resected, to perform atrial cuff plasty. The upper lobe vein and inferior pulmonary vein could be preserved. These techniques of PV elongation and atrial cuff plasty are suitable for both achieving complete resection and lung preservation for lung cancer patients with invasion of the left atrium.

[Preoperative 4D-CT Provided Helpful Evaluation of Aorta Invasion of Left Lower Lobe Lung Cancer].

A 73-year-old woman was diagnosed by bronchoscopic examination with primary left lung cancer (Adenocarcinoma, cT3N0M0, stage IIB), which was closely adjacent to the descending aorta in contrast enhanced computed tomography (CT). This CT did not reveal any invasion of a tumor into the descending aorta, and a dynamic fourth dimension CT (4D-CT) indicated that there was no invasion of the aorta by this tumor, so we decided to perform surgery. The operative procedure was a left lower lobectomy and lymph node dissection with the use of a thoracoscope. An intraoperative finding was that the tumor had not invaded the aorta. There are few reports about the evaluation of vascular invasion using the dynamic 4D-CT. We consider that the dynamic 4D-CT gave very useful information about vascular invasion.

Perioperative pirfenidone treatment for lung cancer patients with idiopathic pulmonary fibrosis.

PURPOSE: To assess the efficacy and feasibility of perioperative pirfenidone treatment (PPT) in lung cancer patients with idiopathic pulmonary fibrosis (IPF). METHODS: The subjects of this retrospective review were 100 patients diagnosed with IPF, who underwent surgical resection for primary lung cancer between January 2011 and April 2018 at our institution. We compared the clinical outcomes of patients treated with pirfenidone (PPT group; n = 28) and those of patients not treated with pirfenidone (non-PPT group; n = 72). RESULTS: The Japanese Association for Chest Surgery (JACS) risk score was significantly higher in the PPT group (p = 0.020, 10.9 vs. 9.4); therefore, we subdivided the groups based on JACS risk score. In the low-risk group, the incidence of postoperative acute exacerbation (AE) both within the postoperative day (POD) 30 and 90 was 0.0% (0/6) and 6.5% (2/31) in the PPT and non-PPT groups, respectively (p = 0.522). In the intermediate/high-risk group, the incidence of postoperative AE was 4.5% (1/22) and 19.5% (8/41) within POD 30 (p = 0.106) and 4.5% (1/22) and 24.4% (10/41) within POD 90 (p = 0.048) in the PPT and non-PPT groups, respectively. No serious pirfenidone-related complications were observed. CONCLUSIONS: Based on our findings, PPT is an effective and feasible prophylactic treatment to reduce postoperative AE.

The impact of perioperative heparin bridging therapy in lung cancer surgery.

PURPOSE: The impact of perioperative heparin bridging (HB) for lung surgery in patients on anti-clotting drugs remains unclear. We performed a retrospective study to assess its effect on surgical safety by comparing HB and non-HB groups. METHODS: This study included 274 consecutive patients on anti-clotting drugs who underwent surgery for lung cancer. Of these, 77 received HB and 197 did not. Propensity score matching extracted 124 patients, consisting of 62 patients with HB and 62 patients without HB. Endpoints were surgical safety. RESULTS: There was no statistically significant difference in the outcomes of surgical safety outcomes between the HB and non-HB group after propensity-score matching, operative time (172 vs. 203 min, p = 0.131), volume of blood loss (60 vs. 70 ml, p = 0.335), need for intraoperative RBC transfusion (3.2 vs. 6.5%, p = 0.680), chest tube drainage volume on the 1st postoperative day (200 vs. 200 ml, p = 0.796), and chest tube placement duration (3 vs. 3 days, p = 0.606). CONCLUSIONS: The influence of perioperative HB on postoperative thromboembolic or bleeding events in lung cancer surgery is not obvious, but its surgical safety appears to be acceptable.