Expression patterns of HNF4α, TTF-1, and SMARCA4 in lung adenocarcinomas: impacts on clinicopathological and genetic features.

INTRODUCTION: HNF4α expression and SMARCA4 loss were thought to be features of non-terminal respiratory unit (TRU)-type lung adenocarcinomas, but their relationships remained unclear. MATERIALS AND METHODS: HNF4α-positive cases among 241 lung adenocarcinomas were stratified based on TTF-1 and SMARCA4 expressions, histological subtypes, and driver mutations. Immunohistochemical analysis was performed using xenograft tumors of lung adenocarcinoma cell lines with high HNF4A expression. RESULT: HNF4α-positive adenocarcinomas(n = 33) were divided into two groups: the variant group(15 mucinous, 2 enteric, and 1 colloid), where SMARCA4 was retained in all cases, and the conventional non-mucinous group(6 papillary, 5 solid, and 4 acinar), where SMARCA4 was lost in 3/15 cases(20%). All variant cases were negative for TTF-1 and showed wild-type EGFR and frequent KRAS mutations(10/18, 56%). The non-mucinous group was further divided into two groups: TRU-type(n = 7), which was positive for TTF-1 and showed predominantly papillary histology(6/7, 86%) and EGFR mutations(3/7, 43%), and non-TRU-type(n = 8), which was negative for TTF-1, showed frequent loss of SMARCA4(2/8, 25%) and predominantly solid histology(4/8, 50%), and never harbored EGFR mutations. Survival analysis of 230 cases based on histological grading and HNF4α expression revealed that HNF4α-positive poorly differentiated (grade 3) adenocarcinoma showed the worst prognosis. Among 39 cell lines, A549 showed the highest level of HNF4A, immunohistochemically HNF4α expression positive and SMARCA4 lost, and exhibited non-mucinous, high-grade morphology in xenograft tumors. CONCLUSION: HNF4α-positive non-mucinous adenocarcinomas included TRU-type and non-TRU-type cases; the latter tended to exhibit the high-grade phenotype with frequent loss of SMARCA4, and A549 was a representative cell line.

Contralateral pneumothorax with postpneumonectomy syndrome: report of 18-year-old case.

We herein report a case of an 18-year-old male with left postpneumonectomy syndrome who underwent a bullectomy for right pneumothorax. The patient underwent a left pneumonectomy at the age of 1 year. At the age of 18 years, he developed right pneumothorax, and radiological findings revealed apical bullae in the right pleural cavity extending into the left atrophic thoracic cavity beyond the upper mediastinum. The right thoracoscopic bullectomy was successful. Modifications of selective lobar ventilation during surgery and thoracoscope position were described.

Matrix metalloproteinase­1 and microRNA­486­5p in urinary exosomes can be used to detect early lung cancer: A preliminary report.

The present study describes a novel molecular-genetic method suitable for lung cancer (LC) screening in the work-place and at community health centers. Using urinary-isolated exosomes from 35 patients with LC and 40 healthy volunteers, the expression ratio of MMP-1/CD63, and the relative expression levels of both microRNA (miRNA)-21 and miRNA-486-5p were measured. MMP-1/CD63 expression ratio was significantly higher in patients with LC than in the healthy controls {1.342 [95% confidence interval (CI): 0.890-1.974] vs. 0.600 (0.490-0.900); P<0.0001}. The relative expression of miRNA-486-5p in male healthy controls was significantly different from that in female healthy controls, whereas there was no significant difference in miRNA-21. Receiver operating characteristic curve (ROC) analysis of MMP-1/CD63 showed 92.5% sensitivity and 54.3% specificity, whereas miRNA-486-5p showed 85% sensitivity and 70.8% specificity for men, and 70.0% sensitivity and 72.7% specificity for women. The logistic regression model used to evaluate the association of LC with the combination of MMP-1/CD63 and miRNA-486-5p revealed that the area under the ROC curve was 0.954 (95% CI: 0.908-1.000), and the model had 89% sensitivity and 88% specificity after adjusting for age, sex and smoking status. These data suggested that the combined analysis of MMP-1/CD63 and miRNA-486-5p in urinary exosomes may be used to detect patients with early-stage LC in the work-place and at community health centers, although confirmational studies are warranted.

Diagnostic utility of trefoil factor families for the early detection of lung cancer and their correlation with tissue expression.

Trefoil factors (TFFs) are upregulated in numerous types of cancer, including those of the breast, the colon, the lung and the pancreas, suggesting their potential utility as biomarkers for screening. In the present study, the clinical relevance of serum or urinary TFFs as biomarkers were comprehensively evaluated and the correlation with TFF expression levels in lung cancer tissue was examined. Serum and urine were collected from 199 patients with lung cancer and 198 healthy individuals. Concentrations of serum and urinary TFF1, TFF2 and TFF3 were measured using ELISA and the potential of TFF levels to discriminate between cancer and non-cancer samples was evaluated. In 100 of the cancer cases, expression of TFF1-3 was analyzed using immunohistochemical staining of paraffin sections. Furthermore, the relationship between TFF levels and clinicopathological factors among these cancer cases was analyzed using immunohistochemistry of tissue specimens, quantified and statistically analyzed. While serum levels of all TFFs measured using ELISA were significantly higher in patients with lung cancer compared with those in healthy individuals, urinary TFFs were lower. Areas under the curve (AUC) of the receiver operating characteristic curves for serum/urinary TFF1, TFF2 and TFF3 were 0.709/0.594, 0.722/0.501 and 0.663/0.665, respectively. Furthermore, the combination of serum TFF1, TFF2, TFF3 and urinary TFF1 and TFF3 demonstrated the highest AUC (0.826). In the clinicopathological analysis, serum TFF1 was higher in the early pathological T-stage (pTis/1/2) compared with the later stage (pT3/4) and TFF2 was higher in the pN0/1 than the pN2 group. With regards to the histological types, urinary TFF1 was higher in squamous cell carcinoma than adenocarcinoma (AC), but TFF2 tended to be higher in AC. Using immunohistochemical analysis, although TFF1 and TFF3 expression showed positive correlation with serum concentrations, TFF2 was inversely correlated. In conclusion, serum and urinary TFF levels are promising predictive biomarkers, and their measurements provide a useful in vivo and non-invasive diagnostic screening tool. In particular, TFF1 and TFF3 could be surrogate markers of clinicopathological profiles of human lung cancer.

[Retrograde S(9+)10 Segmentectomy without Interlobar Fissurelectomy].

BACKGROUNDS: With increase of patients with a small-sized lung cancer, there is an increasing need for minimally invasive lung segmentectomy that can preserve respiratory function. We perform S(9+)10 segmentectomy with retrograde dissection of the pulmonary vein, bronchus, pulmonary artery, in order, without interlober fissurelectomy and staple dissection of the peripheral lung parenchyma. METHODS: Seven patients who underwent retrograde S(9+)10 segmentectomy between June, 2021 and May, 2022 in our hospital were retrospectively reviewed. RESULTS: No patient was converted to the open thoracotomy, without any complications including prolonged air leakage. The average operation time was 171 minutes( range 125 to 221), amount of bleeding was 25 ml( range 0 to 75). Median duration of chest tube insertion was 4 days( range 3 to 6), length of stay after surgery was 6 days (range 5 to 9). Pathologic stage showed pT1mi in 3 patients, pT1a in 3 patients, pT2a in 1 patient. No local recurrence was seen at this time. CONCLUSIONS: Retrograde S(9+)10 segmentectomy is feasible and facilitates interlobar procedure at the time of repeated segmentectomy or completion lobectomy.

[Surgical Case of the Primary Pulmonary Leiomyosarcoma:Report of a Case].

A 70-year-old man was referred for an abnormal chest shadow. Enhanced computed tomography (CT) revealed a well-circumscribed lung tumor of 53 mm in diameter in the left upper lobe with slight enhancement. Positron emission tomography-CT showed a high maximum standardized uptake value for the tumor but no metastasis in the lymph nodes or other organs. Although a definitive diagnosis could not be made by transbronchial biopsy, the tumor was highly suspected to be malignant based on the radiological findings, and a left upper lobectomy with mediastinal lymph nodes dissection was performed for definitive diagnosis and treatment. A pathological examination showed the tumor to be composed of mitotic spindle-shaped cells, which were positive for α-smooth muscle actin, desmin, and caldesmon. The MIB-1 labelling index was 60~70%. According to these pathologic findings, the tumor was identified as a leiomyosarcoma. Metastases to the skin of chest and hilar lymph nodes were noted six months after the surgery for which radiotherapy was performed.

[Thoracoscopic Surgery for Lung Cancer Invading the Superior Chest Wall].

We herein report a case of a 73-year-old man with lung cancer who underwent thoracoscopic right upper lobectomy with combined resection of the superior chest wall. His tumor was 48 mm in diameter and located in the posterior right lung apex involving the chest wall between ribs 1 and 3. The anterior aspects of the ribs 2 and 3 were separated using forceps under thoracoscopic vision. The first rib could be released from the tumor by peeling off the parietal pleura. An 8 cm incision was made posteriorly between the scapula and vertebrae to obtain the posterior aspect of the ribs 2 and 3. After separating the pulmonary vessels and bronchus, en bloc resection of the superior sulcus tumor was completed. Thoracoscopic chest wall resection of the superior sulcus tumor can be an alternative to the Paulson posterolateral-paravertebral thoracotomy approach, which can cause severe postoperative pain and limited range of motion of the shoulder joint.

Idiopathic megacolon complicated by life-threatening giant megacolon and respiratory failure due to diaphragmatic eventration: A case report.

INTRODUCTION AND IMPORTANCE: Giant megacolon requiring emergency surgery is rare. Eventration of the diaphragm associated with giant megacolon is also uncommon. CASE PRESENTATION: We report a 66-year-old male who presented with abdominal distention and progressive dyspnea. After resuscitation following cardiopulmonary arrest, the patient underwent emergent subtotal abdominal colectomy. Eventration of the diaphragm was found postoperatively and his respiratory condition was insufficient to allow liberation. Plication of both diaphragms was performed through left and right thoracotomy via the 8th intercostal space. Postoperatively the patient made a full recovery. CLINICAL DISCUSSIONS: Chronic constipation is a common health condition. A life-threatening condition secondary to chronic constipation is a rarely documented complication. Diaphragmatic eventration that was caused due to chronic megacolon in symptomatic patients requires surgical treatment. CONCLUSIONS: We describe a patient with giant megacolon and diaphragmatic eventration secondary to idiopathic megacolon. The patient underwent subtotal colectomy and diaphragmatic plication and recovered fully.

Immunoglobulin G4-related Pleuritis Complicated with Minimal Change Disease.

A 70-year-old woman with bilateral pleural effusion and respiratory failure was admitted to our hospital. Nephrotic syndrome due to minimal change disease had been diagnosed four months before admission. Because blood tests and a pleural fluid analysis did not reveal the etiology of her condition, we performed a video-assisted thoracoscopic pleural biopsy. No specific thoracoscopic findings were noted. The pathological findings revealed an increase in immunoglobulin G4 (IgG4)-positive cells; IgG4-related pleuritis was diagnosed. Her pleuritis improved with oral corticosteroid therapy. A further investigation was performed on previous kidney samples; however, the etiology of the nephrotic syndrome was not IgG4-related disease but minimal change disease.

TFF-1 Functions to Suppress Multiple Phenotypes Associated with Lung Cancer Progression.

INTRODUCTION: Trefoil Factor (TFF) is a member of a protein family comprised of three isoforms, of which TFF-1 exhibits antithetical functions; promotion or suppression of cell proliferation, survival and invasion, depending on the cancer type. However, the pathobiological function of TFF-1 in lung carcinoma has been still unclear. METHODS: We examined the expression and secretion of TFF-1 using cultured human lung carcinoma cells by immunoblotting, immunofluorescence, enzyme-linked immunosorbent assay and quantitative real-time PCR analyses. The effects of TFF-1 on various phenotypes were analyzed in two cell lines, including those transfected with cDNA encoding TFF-1. Cell proliferation and death were examined by hemocytometer cell counting and by colorimetric viability/cytotoxicity assay. Cell cycle profile, migration and invasion were also examined by flow cytometry, wound healing assay and Matrigel Transwell assay, respectively. The effect of TFF-1 overexpression was confirmed by additional transfection of TFF-1-specific siRNA. RESULTS: Endogenous TFF-1 protein expression and secretion into the media were observed exclusively in adenocarcinoma-derived cell lines. Forced overexpression of TFF-1 drove cell cycle transition, while the proliferation decreased by 19% to 25% due to increased cell death. This cell death was predominantly caused by apoptosis, as assessed by the activation of caspase 3/7. Cell migration was also suppressed by 71% to 82% in TFF-1-transfected cells. The suppressive effect of TFF-1 on proliferation and migration was restored by transfection of TFF-1 siRNA. Moreover, invasion was also suppressed to 77% to 83% in TFF-1-transfected cells. CONCLUSION: These findings reveal that TFF-1 functions as a suppressor of cancer proliferation by induction of apoptosis, cell migration and invasion and thus may provide a synergistic target for potential treatment strategies for human lung carcinoma.

Clinical case of lung spindle cell carcinoma markedly responsive to pembrolizumab.

A 52-year-old man underwent pneumonectomy of the left lung for previously diagnosed primary spindle cell carcinoma (pT4aN1M0, stage III B) with programmed death-ligand 1 expression (tumor proportion score ≥95%) and without epidermal growth factor receptor gene mutation and anaplastic lymphoma kinase fusion gene. However, brain metastasis and chest wall tumor relapse occurred. Considering insufficient improvement with gamma knife treatment for brain metastasis and combination chemotherapy (paclitaxel, carboplatin, and bevacizumab), pembrolizumab monotherapy and palliative irradiation therapy for chest metastases were started after brain tumor volume reduction using craniotomy. Brain edema and chest wall metastases markedly improved following a pseudoprogression of the brain edema accompanied by a performance status decline; this effect continued until 11 cycles of pembrolizumab administration.

Laser-Trélat sign improved after the resection of a tiny ground-grass nodule: a case report.

The Laser-Trélat sign refers to eruptive seborrheic keratoses accompanied by internal malignancies, mainly abdominal advanced ones. Detailed associations remain unclear, and the skin lesions do not improve with the treatment of internal malignancies in half of the patients. Herein, we report a rare case of Laser-Trélat sign that improved after resection of a 0.6-cm pulmonary ground-glass nodule: adenocarcinoma in situ. The patient requested the resection with the hopes of improving the skin lesions, though immediate resection was not indicated oncologically. With informed consent, despite possible failure in improving cutaneous diseases, thoracoscopic partial resection of the right lower lobe was performed. Fortunately, her seborrheic keratoses substantially improved after the resection, without exacerbation. To our knowledge, this is the first report describing such a clinical course. It is essential to inform patients regarding the indication of treatment for internal malignancy and its limitation in improving eruptive seborrheic keratoses.

An aberrant medial basal segmental pulmonary artery (A7b) behind the superior segmental pulmonary vein (V6) in a patient undergoing right superior segment (S6) segmentectomy.

Herein, we report the first case of a patient with lung cancer with an aberrant medial basal segmental pulmonary artery (A7b) behind the superior segmental pulmonary vein (V6) who underwent right superior segment (S6) segmentectomy via uniportal video-assisted thoracoscopic surgery (uVATS). A 56-year-old man with a right lower lobe pure ground-glass nodule (GGN), measuring 12 mm in diameter on computed tomography (CT) had an aberrant A7b branching from the basal pulmonary artery, which was located behind the V6 as detected on 3D CT. The right S6 segmentectomy, via uVATS, for the GGN was performed. The postoperative course was uneventful. The final pathological diagnosis was invasive adenocarcinoma (p-T1bN0M0, stage IA2) with no evidence of disease recurrence at 3-month follow-up. Thoracic surgeons should be aware of the possibility of damaging the A7b when dividing the V6 for S6 segmentectomy, especially during uVATS because of insufficient dorsal visibility.

[Metaplastic Thymoma Underwent Surgery:Report of a Case].

Metaplastic thymoma is a rare histologic variant of thymic epithelial tumors and is characterized by a biphasic growth pattern. We herein report the case of 44-year-old woman who underwent surgery for metaplastic thymoma. Computed tomography scan revealed a well-circumscribed mediastinal tumor: 56 mm in diameter with homogenous enhancement. The tumor was suspected to be a non-invasive thymoma, and thymomectomy with resection of the surrounding thymus was performed using thoracoscopy. The resected tumor measured 60 mm and was grossly well-encapsulated. The cut surface was gray to white and homogenous. Microscopically, the epithelial components took the form of an anastomosing nest to broad trabeculae intertwining with the bundle of spindle cells. Mitosis was not found and the Ki-67 index was < 1%. Cytokeratin 5/6 was strongly positive in the epithelial components composed of polygonal cells. Terminal deoxynucleotidyl transferase positive immature T cells were not observed. Based on these pathologic findings, the tumor was identified as metaplastic thymoma.

Intrapulmonary solitary fibrous tumour: a case report.

Solitary fibrous tumours (SFTs) mainly originate from the visceral pleura and may protrude to the thoracic cavity, but intrapulmonary SFTs are extremely rare. We describe a rare case of SFT arising in the right lung of an 83-year-old man who underwent surgical excision. Chest computed tomography (CT) revealed a 10-mm tumour in the lower lobe of the right lung. The size of tumour gradually increased and reached 17 mm 2 years after the first radiologic examination. Considering the possibility of malignancy, wedge resection of the right lower lobe was performed via video-assisted thoracic surgery. Microscopically, the tumour consisted mainly of spindle-shaped cells. Immunohistochemical staining indicated the tumour was positive for CD34, STAT6, vimentin and bcl-2, but negative for cytokeratins, D2-40 and S-100. Based on the histological findings, the tumour was diagnosed as SFT. The patient has been in good health for 6 months since the surgery.

Diaphragmatic paraganglioma protruding into the right thoracic cavity.

Paragangliomas in the diaphragm are extremely rare. We report the case of a 27-year-old woman with a nonfunctioning paraganglioma protruding superiorly from the right diaphragm. The patient underwent an anterior thoracotomy, and a supradiaphragmatic tumor (70 mm in diameter), which compressed the inferior vena cava and the right hepatic vein, was completely resected by combined partial resection of the right diaphragm and pericardium. To our knowledge, this is the first report of a paraganglioma situated both on the diaphragm and close to the inferior vena cava and hepatic vein. KEY POINTS.

[The Outcome of Second Anatomical Pulmonary Resection for Ipsilateral Metachronous Lung Cancer].

INTRODUCTIONS: When the first intervention for lung cancer is anatomical resection, the ipsilateral repeat anatomical resection for metachronous second lung cancer becomes technically challenging. Herein, we report the outcomes of second anatomical pulmonary resection for ipsilateral metachronous lung cancer at our institution. SUBJECTS: Sixteen consecutive patients[ 10 men and 6 women, average age 70( range 59~81) years] were reviewed in this retrospective study. These patients underwent ipsilateral repeat anatomical resection for metachronous second lung cancer between 2009 and 2020. RESULTS: All case required right-sided lung resections. The previous interventions of patients included upper lobectomy, lower lobectomy, middle lobectomy, S2 segmentectomy, and S6 and S10a segmentectomy in 9, 4, 1, 1, and 1 case, respectively. The second surgical interventions were middle lobectomy, S6 segmentectomy, upper lobectomy, lower lobectomy, S1 segmentectomy, and S2 segmentectomy, in 6, 4, 2, 2, 1, and 1 case, respectively. Postoperative complications occurred in three patients. The median follow-up period was 53.5 months. Three patients died during the follow-up period. Of the 13 patients still alive, 6 had recurrence. The five-year overall survival rate was 80%. CONCLUSIONS: Although only a few cases were assessed, the prognosis after second anatomical pulmonary resection for ipsilateral metachronous lung cancer at our institution was satisfactory.

[Completion Pneumonectomy for the Recurrence of Lung Cancer].

INTRODUCTIONS: The morbidity and mortality after completion pneumonectomy (CP) are reportedly high. We, herein, report the outcomes of CP at our institution. SUBJECTS: Nine consecutive patients [7 men and 2 women, average age of 72 years(range 44~84 years)] who underwent CP for recurrence of lung cancer during 2012~2018 were retrospectively reviewed. RESULTS: Right-sided sleeve CP was performed in two cases and left-sided CP in seven cases. The indications for surgery were lymph node metastasis of the cancer, pulmonary metastasis, and bronchial stump recurrence in 4, 3, and 2 cases, respectively. Postoperative complications occurred in six patients. One of the patients who underwent right sleeve pneumonectomy developed bronchopleural fistula and died 68 days after the surgery. The mean follow-up period was 33 months, and four patients died during follow-up. Of the 5 patients still alive, 4 had no recurrence and 1 had recurrence in the stump of the main bronchus. The five-year overall survival rate was 78%. CONCLUSIONS: Although only few cases were assessed, the prognosis after CP at our institution was relatively good.

An aberrant mediastinal medial basal segmental pulmonary artery (A7a) in a patient with lung cancer: a case report.

BACKGROUND: Mediastinal branching of the A7a from the right main pulmonary artery (PA) is extremely rare. Herein, we report a patient with an aberrant mediastinal A7a who underwent right basal segmentectomy for lung cancer. CASE PRESENTATION: A 73-year-old man was referred to our department for a right lower lobe nodule measuring 18 mm in diameter on computed tomography (CT). Three-dimensional (3D) CT revealed mediastinal A7a branching from the right main PA. As the patient had undergone colectomy for advanced ascending colon cancer, the nodule was suspected to be a metastasis from the colon primary, and thus, basal segmentectomy of the right lung was performed. Intraoperatively, the A7a was observed behind the V4+5 and middle lobe bronchus. The pathological diagnosis was combined small cell carcinoma with an adenocarcinoma component (p-T1cN0M0, stage IA3). The patient subsequently received adjuvant chemotherapy for colon cancer. At 1-year postoperative follow-up, there was no evidence of disease. CONCLUSION: This is the first report describing an aberrant mediastinal A7a branching from the right main PA. It is important to obtain accurate information about variations of the PA using 3D-CT for safe anatomical pulmonary resection.