Impact of Travel Distance on Surgical Outcomes of Patients Surgically Treated for Non-Small Cell Lung Cancer: A Single-Center Study in Ehime, Japan.

Travel burden is a poor prognostic factor for many cancers worldwide because it hinders optimal diagnosis and treatment planning. Currently, the impact of travel burden on survival after surgery for non-small cell lung cancer (NSCLC) in Japan is largely unexplored. We examined the impact of travel distance on the postoperative outcomes of patients with NSCLC in Ehime Prefecture, Japan. The data of 1212 patients who underwent surgical resection for NSCLC were retrospectively reviewed. Patients were divided into quartiles based on the travel distance from their home to the hospital (≤ 13 km, 13-40 km, 40-57 km, and > 57 km) in Ehime Prefecture. We found no significant differences among the quartiles in baseline clinicopathological characteristics, including sex, smoking status, histology, surgical procedure, clinical stage, and pathological stage. Overall survival (OS) and relapse-free survival (RFS) also were not significantly different among the travel distance quartiles. We conclude that travel distance did not impact OS or RFS among patients with NSCLC who underwent surgical resection at our institution.

Benign Mesothelial Cells in transbronchial biopsy specimens: A potential diagnostic pitfall for lung cancer.

Bronchoscopy is a common diagnostic procedure used to identify lung cancer. Specimens acquired through transbronchial biopsy are pivotal in the diagnosis and molecular characterization of this disease. The occurrence of benign mesothelial cells during a transbronchial biopsy (TBB) is relatively rare. Furthermore, these lesions can sometimes be erroneously identified as malignant, potentially resulting in unwarranted or inappropriate treatment for patients with and without lung cancer. In this retrospective analysis, we examined 619 TBB cases at our institute from 2019 to 2021. Benign mesothelial cells were identified via immunohistochemical studies in eight (1.3%) of 619 cases. These cells were classified into three patterns based on their cellular morphology: monolayer, lace, and cobblestone. Recognizing this phenomenon during the procedure is crucial to accurately distinguish benign mesothelial cells from their cancerous counterparts.

A Case of Mediastinal Localized Malignant Pleural Mesothelioma Successfully Treated by Chemotherapy and Conversion Surgery.

Localized malignant mesothelioma is a rare disease and little is known about its treatment strategy. We herein report a case of localized malignant pleural mesothelioma that had infiltrated into the anterior mediastinum, which was successfully treated using chemotherapy and conversion surgery. A 63-year-old man with a mediastinal tumor was referred to our hospital. Pathologic analysis of the biopsy specimen showed malignant mesothelioma. Significant tumor shrinkage by cisplatin and pemetrexed was observed and he underwent radical surgery via a median sternotomy. The patient has been disease free for 12 months.

Ruptured metastatic liver tumor secondary to a thymoma: a case report.

We report a case of rupture of a synchronous metastatic liver tumor secondary to a thymoma. A 56-year-old woman was referred to our hospital with acute abdomen. Computed tomography (CT) revealed a 10 cm diameter tumor in the left lateral segment of the liver, together with ascites, which was suggestive of intra-abdominal bleeding. She was in stable condition and hemostasis was confirmed by angiography. CT also revealed a mass in the anterior mediastinum. Elective laparoscopic left lateral segmentectomy was performed to make a pathological diagnosis and for radical resection. No peritoneal dissemination was observed and the liver tumor was curatively resected. The patient subsequently underwent thymectomy. The pathological diagnoses were thymoma with the liver metastasis. Currently, at 30 months post-treatment, she has had no tumor recurrence. Rupture of a metastatic liver tumor secondary to a thymoma is a rare condition; careful preoperative management and aggressive treatment might improve the patient's prognosis.

Quality of life after partial lung resection with uniportal versus 3-port video-assisted thoracoscopic surgery: a prospective randomized controlled study.

PURPOSE: The effect of uniportal video-assisted thoracoscopic surgery (uni-VATS) versus that of conventional VATS on postoperative quality of life (QOL) is unclear. This prospective randomized controlled study compared uni-VATS and conventional 3-port VATS in terms of QOL and patient satisfaction. METHODS: The subjects of this study were 84 patients with pulmonary nodules or bullous formation, randomized to undergo uniportal or conventional 3-port video-assisted thoracoscopic partial lung resection. The primary endpoint was postoperative pain, assessed using a numeric rating scale on postoperative day (POD) 1. RESULTS: No differences were found in the numeric rating scale on POD 1 after uni-VATS and conventional 3-port VATS. There were also no differences in blood loss, operative time, complication rate, surgical margin, analgesic requirement, vital capacity (VC), forced expiratory volume in 1 s (FEV1), the 6-min walk test (6MWT), C-reactive protein (CRP) levels, white blood cell count (WBC), or duration of chest tube drainage and hospital stay. Differences were found in the numeric rating scale on days 2, 3, 5, and 10 and in the patient satisfaction score on PODs 5 and 10. CONCLUSIONS: Uni-VATS is associated with less chest pain and better patient satisfaction in the short term but without differences in complication rates or surgical margins from the lesions. CLINICAL TRIAL REGISTRY NUMBER: University Hospital Medical Information Network Clinical Trial Registry (UMIN000015340 http://www.umin.ac.jp/english/ ).

A case of thoracic endometriosis-related pneumothorax in a menopausal woman.

Thoracic endometriosis-related pneumothorax (TERP) or thoracic endometriosis syndrome (TES) usually occurs in women of childbearing age and affects the right thorax. Menopausal and left-sided cases are rare. A case of left-sided TERP in a postmenopausal woman after adjuvant endocrine therapy for breast cancer is reported. A 51-year-old woman underwent video-assisted thoracic surgery for recurrent left pneumothorax. Immunohistological examination of the resected specimen from the apical bleb and a diaphragmatic blueberry spot demonstrated thoracic endometriosis. Even in the case of a left-sided pneumothorax in a menopausal woman, clinicians should be aware of the possibility of TERP.

Two cases of granuloma mimicking local recurrence after pulmonary segmentectomy.

BACKGROUND: Fluorodeoxyglucose (FDG)-positron emission tomography (PET)/CT is the most sensitive non-invasive imaging method for the detection of tumor metastasis and recurrence, but sometimes reveals false-positive results. Herein, we report two cases of false-positive results on PET/CT scans along with elevated serum carcinoembryonic antigen (CEA) levels, mimicking local recurrence after pulmonary segmentectomy. CASE PRESENTATION: Case 1; A 75-year-old woman underwent thoracoscopic left basal segmentectomy for primary lung cancer. Follow-up at 6 months after the surgery revealed serum CEA level elevation and chest CT showed a nodule measuring 25 × 22 mm in the residual left lower lobe. PET/CT revealed FDG uptake in the nodule diagnosed as local recurrence of lung cancer, and the patient underwent partial resection of the nodule. Microscopic examination of the resected specimen revealed granuloma caused by polyglycolic acid (PGA) sheet. Case 2; A 58-year-old man underwent VATS right S1 segmentectomy for lung metastasis from rectal carcinoma. Serum CEA levels gradually increased after surgery, and PET/CT revealed FDG uptake in the stump diagnosed as local recurrence of the lung metastasis. The patient underwent completion lobectomy 6 months after the segmentectomy, and the pathology of the resected specimen revealed an inflammatory granuloma caused by PGA suture. CONCLUSIONS: Although suture and stapler granulomas have been reported, granuloma caused by PGA sheets has never been reported. Postoperative recurrence of lung cancer should be diagnosed with not only PET/CT scans and serum tumor markers but also pathological findings, to avoid unnecessary treatment such as chemotherapy, radiation, and difficult reoperation.

Hoarseness after radical surgery with systematic lymph node dissection for primary lung cancer.

OBJECTIVES: Radical surgery with systematic upper mediastinal node dissection for primary lung cancer can cause recurrent laryngeal nerve (RLN) paralysis, but this is poorly reported. METHODS: We retrospectively reviewed the clinical data for consecutive patients who underwent radical surgery for primary lung cancer with an observation period of at least 12 months. During follow-up, hoarseness and vocal fold movement were assessed clinically and laryngoscopically, respectively. RESULTS: Of the 365 patients included in this study, 22 (6.0%) experienced hoarseness as a complication. All 22 patients who experienced hoarseness had undergone upper mediastinal node dissection. Although 1 of the 22 patients refused to undergo laryngoscopy, we assessed the vocal fold movement in the remaining patients (95.5%). Among these, 5 patients (23.8%) had right RLN paralysis, and 15 (71.4%) had left RLN paralysis and showed no sign of RLN paralysis. Over 1-24 months, vocal cord movement improved in 61.1% (11/18); and over 1-28 months, hoarseness improved in 72.7% (16/22). All patients with right RLN paralysis improved without further treatment. CONCLUSIONS: We conclude that extensive follow-up is necessary to discern whether hoarseness is a temporary or permanent complication of radical surgery in patients with primary lung cancer who have undergone systematic lymph node dissection.

Use of the forced-oscillation technique to estimate spirometry values.

PURPOSE: Spirometry is sometimes difficult to perform in elderly patients and in those with severe respiratory distress. The forced-oscillation technique (FOT) is a simple and noninvasive method of measuring respiratory impedance. The aim of this study was to determine if FOT data reflect spirometric indices. PATIENTS AND METHODS: Patients underwent both FOT and spirometry procedures prior to inclusion in development (n=1,089) and validation (n=552) studies. Multivariate linear regression analysis was performed to identify FOT parameters predictive of vital capacity (VC), forced VC (FVC), and forced expiratory volume in 1 second (FEV1). A regression equation was used to calculate estimated VC, FVC, and FEV1. We then determined whether the estimated data reflected spirometric indices. Agreement between actual and estimated spirometry data was assessed by Bland-Altman analysis. RESULTS: Significant correlations were observed between actual and estimated VC, FVC, and FEV1 values (all r>0.8 and P<0.001). These results were deemed robust by a separate validation study (all r>0.8 and P<0.001). Bias between the actual data and estimated data for VC, FVC, and FEV1 in the development study was 0.007 L (95% limits of agreement [LOA] 0.907 and -0.893 L), -0.064 L (95% LOA 0.843 and -0.971 L), and -0.039 L (95% LOA 0.735 and -0.814 L), respectively. On the other hand, bias between the actual data and estimated data for VC, FVC, and FEV1 in the validation study was -0.201 L (95% LOA 0.62 and -1.022 L), -0.262 L (95% LOA 0.582 and -1.106 L), and -0.174 L (95% LOA 0.576 and -0.923 L), respectively, suggesting that the estimated data in the validation study did not have high accuracy. CONCLUSION: Further studies are needed to generate more accurate regression equations for spirometric indices based on FOT measurements.

Two Young Women with Left-sided Pneumothorax Due to Thoracic Endometriosis.

Pneumothorax associated with thoracic endometriosis (TE) generally occurs in women around 30 years old and it usually affects the right pleural cavity. We herein report two cases of TE associated with left-sided pneumothorax in young women. The prevalence of TE in younger patients may be underestimated if these cases are treated as spontaneous pneumothorax. Pneumothorax occurring in younger patients has not been reported to show laterality. TE-related or catamenial pneumothorax in young women must therefore represent a different clinical entity from the condition seen in older patients.

Combined atypical carcinoid tumour and squamous cell carcinoma of the lung.

A 71-year-old man diagnosed with lung cancer in the right lower lobe with invasion to the middle lobe underwent right lower and middle lobectomy with mediastinal lymph node dissection. The cancer was pathologically diagnosed as stage IIB (pT3N0M0) with combined squamous cell carcinoma and an atypical carcinoid tumour. To the best of our knowledge, this is the first report of a combined atypical carcinoid tumour and non-small cell lung cancer. This case further expands the histological spectrum of combined neuroendocrine tumours.

A Case of Mediastinal Granular Cell Tumor with Horner's Syndrome.

Granular cell tumor (GCT) is found in various organs but is rare in the mediastinum. We report a case of mediastinal GCT in a 19-year-old woman who presented with left ptosis and miosis. CT and MRI revealed a 29-mm well-circumscribed tumor located close to the first thoracic vertebra with features suggesting a neurogenic tumor. The tumor was completely excised using single-port video-assisted thoracoscopic surgery. Histopathological and immunohistochemical analysis revealed that the tumor was a benign GCT. Postoperatively, left ptosis and miosis had improved slightly. To our knowledge, this is the first report regarding mediastinal GCT presenting with preoperative Horner's syndrome.

Pulmonary tumor thrombotic microangiopathy diagnosed antemortem and treated with combination chemotherapy.

A 29-year-old man developed a persistent dry cough. Chest high-resolution computed tomography (HRCT) revealed centrilobular ultrafine granular shadows scattered in all lung fields. A lung biopsy with video-assisted thoracoscopic surgery revealed findings compatible with pulmonary tumor thrombotic microangiopathy (PTTM). However, the primary tumor was not identified. Combination chemotherapy with S-1 and cisplatin decreased his cough and improved the chest HRCT findings. The illness, however, gradually became difficult to control. He eventually developed pulmonary hypertension and died. Typically, an antemortem diagnosis of PTTM cannot be made. In this case, the diagnosis of PTTM and combination chemotherapy improved the chest HRCT findings, respiratory symptoms, and prognosis.

Prognostic and predictive implications of HER2/ERBB2/neu gene mutations in lung cancers.

BACKGROUND: Activating mutation in the kinase domain of the human EGF receptor 2 (HER2) gene (also known as ERBB2 or neu) is reported to be present in a small fraction of lung adenocarcinomas. However its prognostic and predictive implications are not yet established. PATIENTS AND METHODS: We examined 504 Japanese lung cancer patients who underwent pulmonary resection for HER2 mutations by direct sequencing and evaluated their prognostic and predictive implications. Updated prognostic data of 14 Japanese patients with HER2 mutation from previous two reports were also gathered. RESULTS: HER2 mutations were identified in 13 of 504 cases (2.6%). Patients with HER2 mutations were common in female, nonsmokers and adenocarcinomas as those with EGFR mutations. When confined to the subgroup of nonsmokers with adenocarcinoma or adenosquamous cell carcinoma without EGFR mutations, the frequency of HER2 mutations was 14.1% (11/78). There was no difference in the overall survival of patients with HER2 mutations, compared with patients harboring EGFR mutations and patients harboring wild types for both EGFR and HER2. Within the patients with HER2 mutation, two of three with TP53 mutation and one of 13 without TP53 mutation died of the disease, suggesting negative prognostic role of the TP53 mutation. Three patients with HER2 mutations did not respond to platinum-based chemotherapy and EGFR-TKIs. Of note, one patient with the most common HER2 mutations, YVMA776-779ins, responded to trastuzumab plus vinorelbine after failure of multiple round of platinum-based chemotherapy and gefitinib. CONCLUSION: HER2 mutations are present in a subset of patients with lung cancer having distinct clinical features. HER2 mutations were not associated with the prognosis of patients with lung cancers. Patients with HER2 mutations might benefit from anti-HER2 therapy.

Molecular characterization of chronic obstructive pulmonary disease-related non-small cell lung cancer through aberrant methylation and alterations of EGFR signaling.

BACKGROUND: The aim of this study was to evaluate the molecular influence of chronic obstructive pulmonary diseases (COPD) on the pathogenesis of non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: The methylation profiles of 12 genes, and the epidermal growth factor receptor (EGFR) and KRAS mutations were determined for samples from 229 NSCLC patients. In addition, protein expression of EGFR and HER2 in 116 NSCLCs was analyzed based on the presence or absence of COPD. RESULTS: IL-12Rbeta2 and Wif-1 methylation and HER2 overexpression were more frequent events in the COPD group. Eighty nonmalignant lung tissues had no correlation with any molecular changes between the COPD and the non-COPD group. EGFR mutation was significantly higher in the non-COPD group, while EGFR expression was inversely correlated with %FEV1.0. In the COPD group, unmethylated SPARC and sFRP-2 genes or a negative CpG island methylator phenotype (CIMP) was a negative prognostic factor, while methylation of p16(INK4A) and WNT antagonist genes was a negative prognostic factor in the non-COPD group. CONCLUSIONS: Novel characteristics of COPD-related NSCLC were identified by examination of methylation profiles and alterations of EGFR signaling. In consideration of the high sensitivity to smoking in patients with COPD, NSCLC with COPD might be a distinct population of smoke-related NSCLC, the genetic profile of which is quite different from non-COPD NSCLC.

Solitary lung metastasis diagnosed 30 years after surgery for thyroid cancer.

A 75-year-old woman with a history of extrapulmonary malignancies (ie, thyroid cancer and colon cancer) underwent a lobectomy for a solitary nodule in the left lung. Pathologic examination showed a lung metastasis from papillary thyroid cancer treated 30 years earlier. Solitary metastasis to the lung from thyroid cancer is unusual, and our case presented the long interval from initial treatment to the identification of metastasis. A careful follow-up is mandatory, and one should keep in mind the delayed metastasis in the patient with differentiated thyroid cancer.

Oncogene mutations, copy number gains and mutant allele specific imbalance (MASI) frequently occur together in tumor cells.

BACKGROUND: Activating mutations in one allele of an oncogene (heterozygous mutations) are widely believed to be sufficient for tumorigenesis. However, mutant allele specific imbalance (MASI) has been observed in tumors and cell lines harboring mutations of oncogenes. METHODOLOGY/PRINCIPAL FINDINGS: We determined 1) mutational status, 2) copy number gains (CNGs) and 3) relative ratio between mutant and wild type alleles of KRAS, BRAF, PIK3CA and EGFR genes by direct sequencing and quantitative PCR assay in over 400 human tumors, cell lines, and xenografts of lung, colorectal, and pancreatic cancers. Examination of a public database indicated that homozygous mutations of five oncogenes were frequent (20%) in 833 cell lines of 12 tumor types. Our data indicated two major forms of MASI: 1) MASI with CNG, either complete or partial; and 2) MASI without CNG (uniparental disomy; UPD), due to complete loss of wild type allele. MASI was a frequent event in mutant EGFR (75%) and was due mainly to CNGs, while MASI, also frequent in mutant KRAS (58%), was mainly due to UPD. Mutant: wild type allelic ratios at the genomic level were precisely maintained after transcription. KRAS mutations or CNGs were significantly associated with increased ras GTPase activity, as measured by ELISA, and the two molecular changes were synergistic. Of 237 lung adenocarcinoma tumors, the small number with both KRAS mutation and CNG were associated with shortened survival. CONCLUSIONS: MASI is frequently present in mutant EGFR and KRAS tumor cells, and is associated with increased mutant allele transcription and gene activity. The frequent finding of mutations, CNGs and MASI occurring together in tumor cells indicates that these three genetic alterations, acting together, may have a greater role in the development or maintenance of the malignant phenotype than any individual alteration.