Risk factor of bronchopleural fistula after general thoracic surgery: review article.

OBJECTIVE: The aim of this article was to clarify recent risk factors for the early bronchopleural fistula after anatomical lung resection. METHODS: Reports on early bronchopleural fistula after anatomical lung resection in adults, including information on risk factors, published between 2006 and 2016 were reviewed and our institutional data were evaluated. The early period was defined as within 30 days from surgery or as described early in the manuscript. RESULTS: A total of seven retrospective observational articles were selected. Four articles investigated lobectomy and pneumonectomy, while the other three articles investigated only pneumonectomy. The surgical procedure, preoperative therapy, complications after surgery, right side, patient age, past history, and tumor residuals were mentioned as risk factors of bronchopleural fistula. Our data concluded that neoadjuvant therapy and a right lower lobe location were risk factors after a lobectomy, while a right side and complete pneumonectomy were risk factors after a pneumonectomy. CONCLUSIONS: Although recent studies have reached nearly the same conclusions as older reports, continuous research of potential risk factor is needed as therapeutic procedures continue to evolve.

A Grading System Combining Tumor Budding and Nuclear Diameter Predicts Prognosis in Resected Lung Squamous Cell Carcinoma.

For lung squamous cell carcinomas, there are no histologic findings that have been universally accepted as prognostic factors. Tumor budding and nuclear grade have been recognized as prognostic factors in other carcinomas. In this study, we investigated whether pathologic findings could determine clinical outcome in Japanese patients with lung squamous cell carcinomas. Tumor slides from surgically resected lung squamous cell carcinomas (1999 to 2012) were reviewed (n=216). Tumors were evaluated for histologic subtypes, differentiation, tumor budding, nuclear diameter, and mitosis. Recurrence-free survival (RFS) and overall survival (OS) were analyzed using the log-rank test and the Cox proportional hazards model. Tumor budding and large nuclei were independent prognostic factors of a worse RFS (P<0.001 and P=0.002, respectively) and a worse OS (P<0.001 and P=0.038, respectively) on multivariate analysis after adjustment for pathologic stage and lymphatic invasion. However, histologic subtypes, differentiation, and mitotic count did not correlate with prognosis. A grading system combining tumor budding and nuclear diameter was an independent prognostic factors of a worse RFS (grade 2 vs. 1, hazard ratio [HR]=2.91; P<0.001, and grade 3 vs. 1, HR=7.60, P<0.001) and a worse OS (grade 2 vs. 1, HR=2.15; P=0.014, and grade 3 vs. 1, HR=4.54, P<0.001). We found that a grading system combining tumor budding and nuclear diameter was a significant prognostic factor among Japanese patients with resected lung squamous cell carcinoma.

Phanerochaete sordida as a cause of pulmonary nodule in an immunocompromised patient: a case report.

BACKGROUND: Phanerochaete sordida is a species of wood rotting fungus, which can degrade lignin, cellulose and hemicellulose contained in wood and other hard-to-biodegrade organic substances. However, to date, there have been no other reports demonstrating that P. sordida can infect humans. CASE PRESENTATION: A 66-year-old Japanese man presented for a mass increasing in size on his left thigh. He had been suffering from rheumatoid arthritis for 18 years and chronic obstructive pulmonary disease for 20 years, for which he was being treated with 5 mg/day prednisolone and 8 mg/week methotrexate. The mass resection was performed two months later, and was diagnosed as malignant fibrous histiocytosis. However, a computed tomography examination for tumor recurrence after surgery showed a newly emergent pulmonary nodule. We therefore decided to resect the nodule by thoracoscopic procedure. Histopathological examination of the excised specimen showed that the lesion was a granuloma, with necrotic tissue and clumping of Aspergillus-like hyphae. Therefore, the nodule was diagnosed as a fungal infection and tissue specimens were cultured microbiologically. However, fungal growth was not observed. We consequently performed genetic analysis using a broad-range polymerase chain reaction. The 28S rRNA sequence demonstrated 100% homology with P. sordida using the NCBI BLAST program against the GenBank DNA databases. CONCLUSIONS: Using broad-range polymerase chain reaction, we identified P. sordida as the causative agent of a pulmonary nodule. These findings indicate that P. sordida may be an additional opportunistic causative organism of pulmonary infection in immunocompromised patients.

Nuclear grade based on transbronchial cytology is an independent prognostic factor in patients with advanced, unresectable non-small cell lung cancer.

BACKGROUND: In patients with resected non-small cell lung cancer (NSCLC), the prognostic value of nuclear grade has been demonstrated. However, among patients with advanced, unresectable NSCLC, the prognostic usefulness of cytological nuclear grade to the authors' knowledge remains unknown. In the current study, the authors used transbronchial cytology to investigate whether nuclear morphometry correlated with clinical outcomes in patients with advanced NSCLC. METHODS: The authors reviewed patients with advanced, unresectable NSCLC who were diagnosed on transbronchial cytology and were treated at the study institution from 2007 through 2015 (97 patients). Nuclear morphometry (including major diameter) was assessed by an image analysis system and small lymphocytes were used as a reference. Overall survival (OS) and progression-free survival (PFS) were estimated using the Kaplan-Meier method, and multivariate analyses were performed using the Cox proportional hazards regression model. RESULTS: In the multivariate analysis, according to the nuclear major diameter as assessed by an image analysis system, a nuclear major diameter >15 µm was an independent prognostic factor of worse OS (hazard ratio [HR], 1.05; P = .003) and PFS (HR, 1.04; P = 0.011). According to the nuclear major diameter as assessed by small lymphocytes, a major diameter of >5 small lymphocytes was an independent prognostic factor of worse OS (HR, 1.32; P<.001) and PFS (HR, 1.20; P = 0.001). A moderately significant correlation between nuclear diameter measurements by an image analysis system and small lymphocytes was observed (P<.001; correlation coefficient, 0.662). CONCLUSIONS: Nuclear grade based on nuclear diameter was found to be independently associated with prognosis in patients with advanced, unresectable NSCLC. Cancer Cytopathol 2016;124:630-40. © 2016 American Cancer Society.

Squamous Cell Lung Cancer Associated With Systemic Sclerosis.

We here describe a 50-year-old woman diagnosed with squamous cell lung cancer (SqLC) with underlying interstitial lung disease (ILD) 14 years after a diagnosis of systemic sclerosis (SSc). We reviewed the literature and collected 21 well-documented cases with SqLC associated with SSc including the present case. Several characteristics of SqLC associated with SSc have been found. First, the average age at diagnosis of SqLC is 57 years, which is much younger than that reported for patients without SSc. Second, SqLC could occur even in never or light smokers, although SqLC usually has a strong association with smoking history. Third, two-thirds of the available cases have ILD. In addition, SqLC developed in the area of ILD in most cases with ILD. Fourth, SqLC generally occurs after a long period from the diagnosis of SSc; the average of this interval reaches 12 years. It would be helpful to know these features so that physicians follow up and treat SSc patients adequately.

[Perioperative Management of Lung Cancer Patients with atrial fibrillation being treated by antiplatelet or anticoagulant therapy].

In an aging society, the high incidence of surgery for the patients with ischemic heart disease(IHD)or atrial fibrillation(Af) under antiplatelet or anticoagulant therapy is a great problem. Interruption of antiplatelet or anticoagulant oral agents in the perioperative period may increase the risk of coronary or cerebral events. We retrospectively reviewed the surgical outcomes for lung cancer patients with IHD or Af. We reviewed 135 patients with lung cancer(41~88 years;97 men) who had preoperative oral administration of antiplatelet or anticoagulant drugs for IHD or Af between 2005 and 2012 at 2 centers, and analyzed retrospectively the perioperative medications and complications. IHD, Af and vasospastic angina(VSA) were complicated in 94, 33 and 8 patients, respectively. Drugeluted and bare-metal stents had been placed in 18 and 19 patients. Oral agents were aspirin in 68 patients, ticlopidine in 10 patients, clopidogrel in 15 patients and warfarin in 25 patients. These agents were stopped 2 to 60 days before surgery. Perioperative heparinization was performed in 22 patients. Oral agents were restarted after confirmation of hemostasis and no need for further invasive treatment. The surgical procedures were lobectomy in 88 patients, segmentectomy in 19 and partial resection in 25. There were no hemorrhagic or thromboembolic complications in a perioperative period except 1 case of pulmonary hemorrhage and 1 case of cerebral infarction. No perioperative hospital death was documented. Short-term interruption of antiplatelet or anticoagulant drugs before lung cancer surgery and heparinization was acceptable from the view of perioperative outcomes.

Chemotherapy followed by surgery on the basis of biomarker examination for patients with advanced non-small cell lung cancer.

BACKGROUND/AIM: We have previously reported that low expression of excision repair cross-complementing-1 (ERCC1), class III ß-tubulin (tubulin), thymidylate synthase (TYMS) and ribonucleotide reductase-M1 (RRM1) is indicative of a favorable prognosis in patients with c-N2,3 non-small cell lung cancer (NSCLC) treated with surgery after induction chemoradiotherapy. In the present study, we prospectively explored the tailor-made treatment menu for induction chemotherapy according to the status of biomarkers, and evaluated the biomarker status pre- and post-chemotherapy. PATIENTS AND METHODS: Twenty-five patients with pathologically-proven NSCLC who were not appropriate candidates for initial surgery were enrolled (October 2010 to June 2012, stage IIIA/B/IV1a/1b;14/5/2/4 respectively). Immunohistochemistry was performed to evaluate intratumoral expression of biomarkers. Epidermal growth factor receptor (EGFR) mutation was evaluated by direct sequencing. Two to four cycles of chemotherapy were performed with or without concurrent radiation (50 Gy). RESULTS: Docetaxel (n=12), pemetrexed (n=4), S-1 (n=4), docetaxel-plus-bevacizumab (n=3), and pemetrexed-plus-bevacizumab (n=2), in combination with platinum were selected for the therapeutic regimen. Twenty-one (84.0%) patients exhibited good partial response, and underwent complete resection without major morbidity or mortality. Of these 21 patients, four achieved a pathologically-complete response (PCR), and 10 achieved a major pathological response. The 3-year overall survival rate was 58.7% for the 25 patients overall, and the 2-year overall survival rate was 73.6% for patients who underwent surgery. Among the 17 patients who underwent resection (except for four with PCR), the status of ERCC1, tubulin, TYMS, RRM1 and EGFR changed markedly after chemotherapy in six patients, eleven patients, eight patients, nine patients and one patient, respectively. CONCLUSION: Chemotherapy followed by surgery on the basis of biomarker examination is a challenging approach for patients with advanced NSCLC who otherwise have poor outcomes. Post-chemotherapy biomarker status changed markedly in many cases.

Innovative method using circulating tumor cells for prediction of the effects of induction therapy on locally advanced non-small cell lung cancer.

BACKGROUND: The existence of circulating tumor cells (CTCs) in patients with lung cancer has been reported. The purpose of this study was to assess whether CTCs are predictive of the pathological effects of induction chemoradiotherapy for patients with non-small cell lung cancer. METHODS: Patients who underwent induction chemoradiotherapy followed by surgery were compared with those who underwent surgery alone. Peripheral and pulmonary venous blood samples from the involved lobe were collected intraoperatively, and the number of CTCs was counted using the CellSearch™ system, an epithelial cell adhesion molecule-based immunomagnetic technique. RESULTS: Of the 9 patients who underwent induction therapy, 4 achieved pathological CR, 4 achieved major response, and 1 achieved minor response. All patients who underwent induction therapy and surgery alone were negative for CTCs in peripheral blood. In the induction therapy group, 4 patients showing pathological CR were negative for CTCs in pulmonary venous blood (pvCTCs) and 5 showing major/minor response were positive (mean, 57.8 cells). The numbers of CTCs in patients showing major/minor response were significantly higher than those in patients showing pathological CR (p = 0.012, Mann-Whitney U test). All 6 patients undergoing surgery alone were positive for pvCTCs (mean, 207.5 cells), showing a significant difference from those undergoing induction therapy (p = 0.038). CONCLUSIONS: The existence of CTCs in pulmonary venous blood reflects pathological non-CR, and therapeutic pathological response may be predicted by pvCTC measurement.

Progressive growth of primary synovial sarcoma of the lung.

An 80-year-old male was admitted because of a giant mass in the left lower lobe of the lung on a routine chest X-ray. Chest computed tomography verified this to be a well-defined heterogeneous mass as described with no associated lymphadenopathy. FDG-PET depicted moderately marginal FDG uptake. The patient underwent a left lower lobectomy and lymphadenectomy. Grossly, the tumor measured 60 × 50 mm and was uniformly filled with a pure white, pudding-like friable substance. No lymph node metastasis was observed microscopically. Histologically, the tumor showed a dense proliferation of rounded or spindled malignant cells with a frequent mitotic activity and an increased nuclear-to-cytoplasmic ratio. The immunohistochemical staining was positive for vimentin, negative for cytokeratin, keratin-wide, EMA, CD34. A SYT-SSX2 fusion gene transcript was detected as a result of RT-PCR analysis. Because of these results, the tumor was diagnosed as a monophasic synovial sarcoma.

Non-surgical closure of post-pneumonectomy empyema with bronchopleural fistula after open window thoracotomy using basic fibroblast growth factor.

Empyema with bronchopleural fistula (BPF) is one of the severest complications following pneumonectomy. Many papers have reported that it is difficult to cure, with a high rate of associated mortality. Closure of the fistula and an appropriate choice of obliteration materials are crucial for successful treatment. However, obliteration is sometimes impractical because of a lack of suitable materials, excessive surgical risk, or lack of patient willingness to undergo the procedure. We report a case of post-pneumonectomy empyema with BPF that was treated by non-surgical closure after open-window thoracotomy (OWT) with the use of basic fibroblast growth factor (bFGF), which was sprayed into the unepithelialized empyema cavity transiting from epidermis and surrounding the fistula. After spraying, the orifice of the OWT was covered by a film dressing. This procedure yielded successful results after two months.

Clear cell carcinoma originating from ectopic thymus.

Cancer of the mediastinum is known to be a relatively rare disease, and clear cell carcinoma in the mediastinum is especially rare. Ectopic thymus is not uncommon, but clear cell carcinoma originating from ectopic thymus has never been reported. We report a case of clear cell carcinoma originating from ectopic thymus in which there was a good response to steroid-supplemented chemoradiotherapy.

Obliteration of empyema space by vascularized anterolateral thigh flaps.

Closure of the fistula and an appropriate choice of obliterating agents are crucial for the treatment of empyema with bronchopleural fistula. The choice of the material to be used for obliteration of the pleural space is a difficult one in some patients, such as those with empyema, developing after omentectomy, laparotomy, posterolateral thoracotomy, and so forth. The use of free anterolateral thigh flaps for obliteration of the pleural space generally needs a satisfactory vascular network around the thorax. We report two successfully treated cases of empyema with bronchial fistula, which were otherwise difficult to manage, in which a free anterolateral thigh musculocutaneous flap anastomosed to the superior thyroid vessels used to obliterate the pleural space.

Characterization of two putative fibronectin-binding proteins of Clostridium perfringens.

Clostridium perfringens is a Gram-positive anaerobic pathogen that causes gas gangrene and food poisoning in humans and animals. Genomic analysis of C. perfringens strain 13 revealed that this bacterium contains two genes (CPE0737 and CPE1847) that encode putative fibronectin (Fn)-binding proteins (Fbps). These genes, named fbpA and fbpB, were found to be constitutively expressed in all three strains (13, NCTC8237, CPN50) of C. perfringens, isolated from gas gangrene of human, that were tested. Both fbpA and fbpB were cloned and His-tagged, recombinant FbpA (rFbpA) and recombinant FbpB (rFbpB) were purified by Ni(2+)-Sepharose column chromatography from transformed Escherichia coli. These recombinant Fbps were shown to bind to Fn, purified from human serum, in a ligand blotting assay. Additionally, Fn bound to these rFbps in a dose-dependent manner in an enzyme-linked immunosorbent assay. Furthermore, it was found that pre-incubation of Fn with either rFbpA or rFbpB inhibited the binding of Fn to C. perfringens cells.

Solitary fibrous tumor of the pleura presenting dry cough induced by postural position.

Solitary fibrous tumor of the pleura is one of the uncommon diseases. About 40% of solitary fibrous tumors of the pleura are of a visceral and peduncled type. Several visceral pleural tumors have motility. A proof of motility of the intrathoracic tumor is useful for preoperative diagnosis. We report a resected case of solitary fibrous tumor of the pleura presenting dry cough induced by postural position.

Mediastinal metastasis of the thyroid papillary carcinoma mimicking thymoma.

Mediastinal tumors are a common condition encountered by general thoracic surgeons, and the most frequent of such tumors is thymoma. However, metastatic mediastinal tumors are rare. Here we report a case of papillary carcinoma of the thyroid to the mediastinum that mimicked thymoma. The patient, a 60-year-old woman who had been treated for thyroid cancer 6 years previously, visited our hospital because of an abnormal shadow in the anterior mediastinum. Radiological findings and laboratory data did not suggest any recurrence of the thyroid cancer, but computed tomography examination revealed a thymoma-like mass. (18)F-Fluoro-2-deoxy-D: -glucose positron emission tomography revealed two lesions: an anterior mediastinal mass and a right breast nodule. We resected both tumors. Histological examination revealed that the mediastinal mass was a metastasis from the thyroid papillary carcinoma, whereas the nodule was an early breast cancer. At the 9-month follow-up examination the patient was well without evidence of recurrence of either cancer.

Mucoid impaction after segmental resection of lung.

Lung segmentectomy is generally considered as a standard procedure in general thoracic surgery. Anatomical variations of pulmonary segmentation may, however, make it difficult to determine the precise area of resection during segmentectomy. Incomplete pulmonary sub-lobar resection may produce unusual radiographic features. Herein, we report a case of bronchial atresia after lung segmentectomy.

Comparison of (18)F-FLT PET and (18)F-FDG PET for preoperative staging in non-small cell lung cancer.

PURPOSE: The nucleoside analog 3'-deoxy-3'-(18)F-fluorothymidine (FLT) has been introduced for imaging cell proliferation with positron emission tomography (PET). We prospectively compared the diagnostic efficacy of FLT PET with that of 2-deoxy-2-(18)F-fluoro-D-glucose (FDG) PET for the preoperative nodal and distant metastatic staging of non-small cell lung cancer (NSCLC). METHODS: A total of 34 patients with NSCLC underwent FLT PET and FDG PET. PET imaging was performed at 60 min after each radiotracer injection. The PET images were evaluated qualitatively for regions of focally increased metabolism. For visualized primary tumors, the maximum standardized uptake value (SUV) was calculated. Nodal stages were determined by using the American Joint Committee on Cancer staging system and surgical and histologic findings reference standards. RESULTS: For the depiction of primary tumor, sensitivity of FLT PET was 67%, compared with 94% for FDG PET (P = 0.005). Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy for lymph node staging on a per-patient basis were 57, 93, 67, 89, and 85%, respectively, with FLT PET and 57, 78, 36, 91, and 74%, respectively, with FDG PET (P > 0.1 for all comparisons). Two of the three distant metastases were detected with FLT and FDG PET. CONCLUSION: In NSCLC, FLT PET showed better (although not statistically significant) specificity, positive predictive value and accuracy for N staging on a per-patient basis than FDG PET. However, FDG PET was found to have higher sensitivity for depiction of primary tumor than FLT PET.

Lobar bronchial atresia demonstrating a cystic lesion without overinflation.

Congenital bronchial atresia (CBA) is an infrequent pulmonary anomaly characterized, in general, by a blindly terminating bronchus, mucoid impaction, and hyperinflation of the peripheral pulmonary parenchyma. We herein report an adult case of lobar bronchial atresia who showed no hyperinflation of the peripheral pulmonary parenchyma.