Case report: Pathological complete response of pregnancy associated pulmonary enteric adenocarcinoma to chemoradiotherapy.

Pulmonary enteric adenocarcinoma (PEAC) is a rare lung adenocarcinoma with morphological features similar to those of primary and metastatic colorectal adenocarcinoma. To date, only a few studies have reported the therapeutic effects of chemoradiotherapy on PEAC. This report describes the case of a 28-year-old woman with pregnancy-related PEAC who presented with left shoulder pain. A superior sulcus tumor was identified in the left thoracic cavity, and the biopsy indicated more than 50% intestinal differentiation components. Moreover, immunohistochemical staining revealed positive CDX2 and CK7 expression. Positron emission tomography-computed tomography, upper endoscopy, colonoscopy, and small intestinal capsule endoscopy revealed no gastrointestinal malignancies. The patient was diagnosed with locally advanced PEAC (clinical stage T4N0M0; stage IIIA). Therefore, the patient was treated with preoperative chemoradiotherapy and underwent gross total resection during surgery. Pathological evaluation of the specimen revealed no residual tumor, indicating that the chemoradiotherapy for PEAC was highly effective. One subsequent brain metastasis was also resected, and the patient has not experienced recurrence in 28 months since this resection and continues to be monitored regularly. This is the first pathologically confirmed report of the use of chemoradiotherapy (carboplatin [CBDCA] and paclitaxel [PTX]) for PEAC and its clinical efficacy. Unlike previous reports, the efficacy of this treatment is attributed to the use of PTX in preoperative chemotherapy and the p21- status of the patient, which may have increased sensitivity to chemoradiation therapy. Therefore, chemoradiotherapy (CBDCA + PTX) may be a viable treatment option for advanced intestinal lung adenocarcinoma.

Prognostic factors of resected pathological stage I lung adenocarcinoma: evaluating subtypes and PD-L1/CD155 expression.

We aimed to compare the prognostic impacts of adenocarcinoma subtypes, programmed death-ligand I (PD-L1), and CD155 expression on patients with resected pathological stage (p-stage) I lung adenocarcinoma. In total, 353 patients with completely resected p-stage I lung adenocarcinomas were retrospectively reviewed. The expression levels of PD-L1 and CD155 in tumour cells from each adenocarcinoma subtype were evaluated using several clinicopathological and histological features, such as the presence of a micropapillary pattern. A total of 52 patients (14.7%) had PD-L1-positive tumours, whereas 128 patients (36.3%) had CD155-positive tumours, with a tumour proportion score of 5% for both PD-L1 and CD155 expression. Compared with patients with other adenocarcinoma subtypes, those with solid-predominant adenocarcinomas were significantly more positive for PD-L1 and CD155. Multivariate analysis showed that PD-L1 expression status was significantly associated with progression-free survival and overall survival, whereas CD155 expression and the presence of a micropapillary pattern were not significantly associated with either parameter. Patients with PD-L1-positive tumours had poorer prognoses than those with CD155-positive tumours. Moreover, PD-L1 and CD155 were significantly expressed in solid-predominant adenocarcinomas. The results of this study suggest that immune checkpoint inhibitors can be used as adjuvants in the treatment of patients with p-stage I adenocarcinoma.

Prognostic impact of PD-L1 and TIGIT expression in non-small cell lung cancer following concurrent chemo-radiotherapy.

We investigated the effect of preoperative therapy for non-small cell lung cancer on programmed death-ligand 1 (PD-L1), programmed death-1 (PD-1), poliovirus receptor (CD155), and T cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif (ITIM) domain (TIGIT) expression and prognosis with the cases of 28 patients received preoperative concurrent chemo-radiotherapy (cCRT) and 27 received preoperative drug therapy. The post-treatment PD-L1 expression was higher in cCRT group than in the drug therapy (50.0% vs 5.0%, p = 0.000), whereas that of CD155 did not significantly differ (40.0% vs 60.0%, p = 0.131). The PD-1 expression was not significantly different between the cCRT and drug therapy groups (51.1% vs 42.9%, p = 0.076), while the TIGIT was significantly higher in the cCRT group (41.5% vs 34.0%, p = 0.008). The patients who received cCRT resulted in elevated PD-L1and TIGIT values had a worse prognosis (p = 0.008). The PD-L1 and TIGIT expression after cCRT was significantly higher than after drug treatment. The cCRT population with high expression of both had a significantly poorer prognosis, indicating elevation of PD-L1 and TIGIT after cCRT as a negative prognostic factor. Combination therapy with anti-PD-L1 and anti-TIGIT antibodies after cCRT may contribute to an improved prognosis.

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.

[Segmental Bronchoalveolar Lavage Provided a Favorable Clinical Course in a Case of Autoimmune Pulmonary Alveolar Proteinosis].

A 49-year-old man was diagnosed with autoimmune pulmonary alveolar proteinosis. Chest computed tomography (CT) showed typical CT findings of pulmonary alveolar proteinosis: thickening of septa with ground-glass opacities in both lung fields. The diagnosis of autoimmune pulmonary alveolar proteinosis (PAP) was based on findings of bronchoalveolar lavage (BAL) fluid with milky appearance and elevated serum titer of anti-granulocyte-macrophage colony-stimulating factor antibody. We decided to perform segmental BAL via bronchoscopy. The surgery was performed under a general anesthesia since the patient had severe hypoxemia and strong cough reflex. Following 3 repeated courses of therapy, his respiratory condition and the ground-glass opacity in both lung fields improved remarkably, with no recurrence in 3 years. There are only a few published case reports in the world of the usefulness of segmental BAL under general anesthesia for PAP. We consider that segmental BAL is a useful therapeutic method for PAP in cases with severe hypoxemia, such as the present patient.

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.

Three Cases of Resection of Late Recurrence of Breast Cancer that Required Differential Diagnosis of Primary Lung Cancer.

We report 3 cases of surgical resection for lung metastasis more than 15 years after initial surgery for breast cancer. Case 1: A 77-year-old woman was referred to our hospital because of a lung nodule in the left lower lobe detected in a computed tomography (CT) scan. She had undergone breast preservation therapy for breast cancer 15 years before the first visit. Left lower lobectomy was performed via video-assisted thoracoscopic surgery (VATS). The pathological diagnosis was lung metastasis of breast cancer, based on positive immunohistochemical staining of estrogen receptor (ER) and gross cystic disease fluid protein 15 (GCDFP-15). Case 2: An 88-year-old woman had undergone a mastectomy for breast cancer 23 years previously. A CT scan revealed a nodule in the upper lobe of the left lung. A wedge resection of the left upper lobe was performed. Because immunostainings for progesterone receptor (PgR) and GCDFP-15 were positive, the pathological diagnosis was metastasis of breast cancer. Case 3: A 78-year-old woman had undergone right mastectomy for the breast cancer 29 years previously. The patient was referred to our hospital because of a nodule in the right lung in a CT scan. Thoracoscopic right upper lobectomy was performed. The pathological diagnosis was lung metastasis of the breast cancer, with immunohistochemical positivity to ER, PgR, and focally to GCDFP-15. A differential diagnosis between primary lung cancer and metastasis of breast cancer on the basis of the findings of a CT scan is often difficult. It is important to obtain the previous clinical information about the breast cancer before VATS, even in patients with a long disease-free interval of more than 15 years.

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.

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.

[Two Resected Cases of Primary Pulmonary Mucosa-Associated Lymphoid Tissue Lymphoma, Differently Diagnosed in Chest Tomography Scan].

Case 1: A 81-year-old man was admitted to our hospital because of a mass shadow on chest x-ray examination. Chest computed tomography (CT) showed a 1.5 cm nodule in the middle lobe of the right lung. We suspected a primary lung cancer and performed video-assisted right middle lobectomy. Histopathological examination showed a white, elastic, hard and solid 30 × 10 × 10 mm nodule with infiltration of small-to-medium-sized lymphocytes that were positive for CD20 and CD79a, and negative for CD10 and Cyclin D1 in immunohistochemical staining. We diagnosed mucosa-associated lymphoid tissue (MALT) lymphoma. Case 2: A 67-year-old woman was admitted to our hospital because of a mass shadow in the right upper lobe on chest x-ray and chest CT. As the lesion had not grow in 1 year, the patient strongly wanted it resected, therefore we performed wedge resetion of the right upper lobe via video-assisted thoracic surgery. Histopathological examination showed a white, elastic, hard and solid 25 × 25 × 16 mm nodule with infiltration of small-to-medium-sized lymphocytes that had positive staining of CD20 and CD79a, and negative staining of CD10 and Cyclin D1. We diagnosed MALT lymphoma. Primary lung MALT lymphoma shows a variety of shadows on chest CT, similar to lung cancer and other inflammatory diseases. Local therapies such as surgery and radiation therapy are effective against early stage MALT lymphoma, but there is no consensus of a standard surgery.