Interdisciplinary Treatment of Malignant Chest Wall Tumors.

BACKGROUND: Chest wall resections for malignant chest wall tumors (MCWTs), particularly those with full-thickness chest wall involvement requiring reconstruction, present a therapeutic challenge for thoracic and plastic reconstructive surgeons. The purpose of this study was to review our experience with chest wall resection for primary and metastatic MCWTs, with a focus on perioperative outcomes and postoperative overall survival (OS). METHODS: All patients who underwent surgical resection for primary and secondary MCWTs at our single institution between 2000 and 2019 were retrospectively analyzed. RESULTS: A total of 42 patients (25 male, median age 60 years) operated upon with curative (n = 37, 88.1%) or palliative (n = 5, 11.9%) intent were reviewed. Some 33 (78%) MCWTs were of secondary origin. Chest wall reconstruction was required in 40 (95%) cases. A total of 13 (31%) patients had postoperative complications and one (2.3%) died perioperatively. The 5-year postoperative overall survival rate was 51.9%. The postoperative 5-year survival rate of 42.6% in patients with secondary MCWTs was significantly lower compared to the figure of 87.5% in patients with primary MCWTs. CONCLUSIONS: In well-selected patients, chest wall resections for primary and secondary MCWTs are feasible and associated with good perioperative outcomes. For secondary MCWTs, surgery can also be performed with palliative intent.

Spread through Air Spaces (STAS) in Solitary Pulmonary Metastases from Colorectal Cancer (CRC).

BACKGROUND: Spread through air spaces (STAS) is a recently described route of tumor invasion associated with poor prognosis in primary lung cancer. Aim of this study was to investigate the presence of STAS and to assess its prognostic significance in patients undergoing pulmonary metastasectomy (PM) for solitary metastases from colorectal cancer (CRC). MATERIALS AND METHODS: All 49 CRC patients (30 male and 19 female, median age 66 years) who underwent PM between January 2008 and December 2015 were retrospectively analyzed. RESULTS: STAS was identified in 26.5% (n = 13) of resected specimens. Location of pulmonary lesions (central vs. peripheral) was assessed based on the available computed tomography imaging (n = 47, 96%). STAS was detected in all five patients with central metastases (100%) versus 7 of 42 (17%) with peripheral metastases (p = 0.0001). Locoregional recurrence occurred in STAS-positive patients (n = 4 of 13 vs. n = 0 of 36), all STAS-negative patients remained recurrence-free (p = 0.003). Median number of alveoli with STAS involvement was four (range from 2 to 9). There was statistically positive relationship between the number of alveoli invaded with STAS and locoregional recurrence of metastases (p = 0.0001). The presence of STAS is not a factor affecting the 5-year overall survival rate (p = 0.6651). CONCLUSION: We identified STAS as a frequent finding in resected CRC lung metastases and found insignificant association with outcome.

Surgery for Pulmonary Metastases: Long-Term Survival in 281 Patients.

BACKGROUND: Despite weak evidence, pulmonary metastasectomy (PM) is widely performed with intent to improve patient survival. Our single-institution analysis aims to evaluate outcomes and to identify factors influencing survival of patients undergoing PM for metastases from wide range of primary tumors. MATERIALS AND METHODS: All patients undergoing curative-intent PM between 2008 and 2018 were retrospectively analyzed. The impact of factors related to primary tumor, metastases, and associated therapy on overall survival (OS) was evaluated using univariable and multivariable Cox proportional hazard models. Cutoff values of continuous variables were determined by a receiver operating characteristic analysis. RESULTS: In this study, 281 patients (178 male, median age 61 years) underwent PM. Two (0.7%) perioperative deaths and 23 (8.2%) major complications occurred. Median interval between the treatment of primary tumor and PM was 21 months. Median size of largest metastasis was 1.4 cm. After the median follow-up of 29 months, 134 patients (47.7%) had died. Five-year OS rate after first PM was 47.1%. Complete resection was achieved in 274 (97.5%) patients. Multivariable analysis identified genitourinary origin (hazard ratio [HR]: 0.30, 95% confidence interval [CI]: 0.15-0.60, p = 0.0008) as independent positive survival prognosticator; incomplete resection (HR: 3.53, 95% CI: 1.40-8.91, p = 0.0077) and age at PM of ≥66 years (HR: 1.97, 95% CI: 1.36-2.85, p = 0.0003) were negative prognosticators. CONCLUSION: The use of PM as a part of multimodal treatment is in selected population justified. Our analysis identified age, primary tumor origin, and completeness of resection as independent survival prognosticators.

Survival and Prognostic Analysis after Pulmonary Metastasectomy for Head and Neck Cancer.

BACKGROUND: There is no consensus on the value of pulmonary metastasectomy (PM) for head and neck cancer (HNC). The aim of our single-institution study was to evaluate outcomes and to examine factors influencing 5-year survival of patients undergoing resections for HNC lung metastases. METHODS: All HNC patients undergoing curative-intent PM between January 2008 and December 2018 were retrospectively analyzed. The impact of factors related to primary tumor, metastases, and associated therapy on patient survival was evaluated using the univariable Cox proportional hazard model. Cutoff values of continuous variables were determined by a receiver operating characteristic analysis. RESULTS: In total, 44 patients (32 males and 12 females, with a median age of 65 years) underwent PM for metastatic HNC. There was one perioperative death, and major complications occurred in 2 (4.5%) patients. The median interval between the treatment of primary tumor and PM was 19.4 months (range: 0-151 months). Median size of the largest resected pulmonary lesion was 1.3 cm (range: 0.3-6.9 cm). Mean follow-up was 21 months (range: 0-123 months), and 5-year overall survival (OS) rate after the first PM was 41%. Resection was complete (R0) in all patients. Larger size of pulmonary metastasis (≥1.4 cm; hazard ratio: 4.49; 95% confidence interval: 1.79-11.27) was a significantly negative prognostic factor. CONCLUSION: Despite the lack of randomized controlled trials, PM for HNC is a reasonable therapeutic option with favorable survival in a selected population. In patients with larger pulmonary lesions, shorter OS after PM is to be expected.

Negative Pressure Wound Therapy Combined With Instillation for Sternoclavicular Joint Infection.

BACKGROUND: There is no consensus on the management of spontaneous sternoclavicular joint infection (SCJI). Negative pressure wound therapy (NPWT) has been widely accepted for SCJI. We reviewed our experience with the management of this condition comparing NPWT alone and NPWT combined with instillation and dwell time. METHODS: We retrospectively analyzed the data of patients with spontaneous SCJI treated in our thoracic unit. RESULTS: From March 2008 to October 2019, 27 patients (21 men and 6 women) underwent NPWT combined with muscle flap transfer after necrosectomy and chest wall resection for SCJI. The median age was 57.1 years (range, 35 to 85). Depending on management, the patients were divided into two groups: 16 patients with NPWT in group 1, and 11 patients with NPWT combined with instillation and dwell time in group 2. The severity of SCJI, extent of chest wall resection, and type of muscle flap were not significantly different (P = .35, P = .858, P = .705, respectively). Median duration of hospital stay and NPWT were shorter in group 2 (30 vs 25 days, and 20 vs 16 days, respectively). The required wound dressing changes were significantly lower in group 2 (P = .008). Statistical trend to higher bacterial eradication in group 2 was noted (P = .093). Postoperative complications including SCJI recurrence, wound seroma, and dehiscence were not significantly different between groups (P = .269). CONCLUSIONS: The NPWT combined with instillation and dwell time appears a useful strategy in patients with SCJI, leading to higher incidence of bacterial eradication and shorter wound care.

Major Pathologic Response after Induction Therapy Has a Long-Term Impact on Survival and Tumor Recurrence in Stage IIIA/B Locally Advanced NSCLC.

BACKGROUND: Major pathologic response (MPR) determines favorable outcome in locally advanced non-small cell lung cancer after induction therapy (IT) followed by lung resection. The aim of this retrospective study was to identify the prognostic relevance of MPR in long-term interval. METHODS: In 55 patients, the survival rate according to MPR and non-MPR was estimated by Kaplan-Meier method and compared using log-rank, Breslow, and Tarone-Ware tests. RESULTS: The IT included chemoradiation with 50.4 Gy (range: 45-56.4 Gy) combined with platinum-based chemotherapy in 52 patients (94.5%) and platinum-based chemotherapy in 3 patients (5.5%). Perioperative morbidity and 30-day mortality were 36 and 3.6%, respectively. The estimated 5-year postoperative and progressive-free survivals were statistically significantly improved in MPR versus non-MPR with 53.5 versus 18% and 49.4 versus 18.5%, respectively. According to the log-rank, Breslow, and Tarone-Ware tests, the MPR demonstrates prognostic significance in early, long-term, and whole postoperative interval. CONCLUSION: MPR is associated with a robust correlation to long-term postoperative and recurrence-free survival improvement, and can potentially simplify the multidisciplinary debate and allow further stratification of adjuvant treatment in multimodality therapy.

Pulmonary metastasectomy for sarcoma-survival and prognostic analysis.

BACKGROUND: Pulmonary metastasectomy (PM) has commonly been performed in patients with controlled metastatic sarcoma. We reviewed our single-institution experience with pulmonary resections for sarcoma to analyse clinical outcome and to identify prognostic factors associated with patient survival. METHODS: All sarcoma patients undergoing curative intent PM between 2008 and 2014 were retrospectively analysed. Factors related to primary tumour, metastases, applied therapy, systematic inflammation and preoperative nutritional condition, associated with survival after PM were evaluated using the univariable Cox proportional hazard model. Cut-off values of continuous variables were determined by a receiver operating characteristic (ROC) analysis. RESULTS: In total, 33 patients (19 male and 14 female, median age 55 years) underwent PM for metastatic sarcoma. There were no perioperative deaths; major complications occurred in 5 (15.2%) patients. The median interval between the treatment of primary tumour and PM was 16 months (range, 0-171 months). The median size of the largest pulmonary lesion was 1.3 cm. Mean follow-up was 37 months (range, 1-100 months) and the 5-year overall survival (OS) rate after first PM was 40.4%. Resection was complete (R0) in 31 (93.9%) patients. In univariable analysis, a shorter interoperative interval [<30 months, hazard ratio (HR) 5.05, 95% confidence interval (CI): 1.15-22.19] and grade 3 (G3) sarcoma (HR 3.52, 95% CI: 1.01-12.25) were significant negative prognosticators. CONCLUSIONS: Despite the lack of randomized controlled trials PM for sarcomatous disease is a reasonable therapeutic option with acceptable survival in a selected patient population. In sarcoma patients with a shorter interoperative interval and G3 tumour, shorter survival after PM can be expected.

Sternal resection and reconstruction for secondary malignancies.

BACKGROUND: Limited data on sternal and/or anterior chest wall resections for secondary malignancies exist. The purpose of this study was to examine the perioperative outcomes and postoperative overall survival (OS) in patients who underwent sternal and/or anterior chest wall resections for secondary sternal tumors (SSTs). METHODS: A retrospective analysis of all patients who underwent resection of SSTs at single institution between 2000 and 2016 has been performed. OS was estimated using the Kaplan-Meier method. RESULTS: Ten patients underwent sternal and/or anterior chest wall resection for SSTs with curative (70%) or palliative (30%) intent. Two (20%) patients underwent complete and 8 (80%) partial sternal and/or anterior chest wall resection. There were no perioperative deaths, major complications occurred in 3 (30%) patients. Tumor resection was complete (R0) in 5 (50%) patients. The 5-year OS rate was 40%. No OS difference in R0 vs. R1 resections was observed. CONCLUSIONS: Sternal and/or anterior chest wall resections for SSTs can be performed with low morbidity and mortality. Complete SST resection does not assure favorable OS. Sternal resections can be considered palliative treatment option in patients with stable stage IV disease with isolated sternal involvement.

Pathologic complete response after induction therapy-the role of surgery in stage IIIA/B locally advanced non-small cell lung cancer.

BACKGROUND: Pathologic complete response (pCR) is dominant prognostic factor determining favorable outcome in locally advanced non-small cell lung cancer (NSCLC) after induction therapy (IT). There is no non-operative diagnostics that adequately estimates the pCR. Aim of this retrospective study was to assess the correlation between clinical and pathological factors in patients with pCR. METHODS: Twenty-five patients with pCR after curative lung resection following IT were assessed using univariate and multivariate Cox regression and descriptive analysis. The survival rate was estimated by Kaplan-Meier method. RESULTS: The IT included chemoradiation with median doses of 50.4 Gy (range, 45-59.4 Gy) combined with platinum-based chemotherapy in 23 patients (92%) and induction platinum-based chemotherapy in 2 patients (8%). Clinical tumor stage before IT was IIIA in 21, IIIB in 4 patients. Mean interval between IT and surgery was 8.1±3.0 weeks. Perioperative morbidity and 30-day mortality was 32% and 4%, respectively. There was no significant correlation of pCR and different clinical and pathological factors. The estimated 5-year long-term survival (LTS) and progressive-free survival (PFS) was 57% and 54%, respectively. The median LTS and PFS was not reached. CONCLUSIONS: pCR in patients with locally advanced NSCLC following IT is an independent prognostic factor, without correlation with pathological and clinical factors. Non-operative accurate assessment of pCR is currently impossible. Surgical resection enables secure identification of pCR and might improve the patient stratification for additive therapy.

[Lung Resection after Definitive and Neo-Adjuvant Chemoradiation for Stage IIIA/B Locally Advanced Non-Small Cell Lung Cancer: a Retrospective Analysis]. / Lungenresektion nach definitiver und neoadjuvanter Radiochemotherapie im Stadium IIIA/B des lokal fortgeschrittenen nicht kleinzelligen Lungenkarzinoms: eine retrospektive Analyse.

BACKGROUND: The outcomes of so called "salvage" resections after definitive chemoradiation vs. curative resections after neoadjuvant chemoradiation therapy (IT-resection) in patients with stage IIIA/B locally advanced non-small cell lung cancer have rarely been compared. The aim of our study was to compare perioperative results, postoperative and recurrence-free survival and to identify relevant prognostic survival factors for both therapy strategies. PATIENTS AND METHODS: Between June 2008 and May 2017, 43 patients underwent pulmonary resection following induction therapy (group 1) and 14 patients underwent salvage resection after definitive chemoradiation (group 2). Retrospective analysis was performed of demographic factors, tumour stage and location, initial therapy, preoperative regression status, perioperative morbidity and mortality, postoperative and recurrence-free survival. RESULTS: In group 2, significantly higher radiation dose was applied (p < 0.001) and the interval between chemoradiation and lung resection was significantly longer (p = 0.02). In addition, significantly higher perioperative blood loss and more frequent blood transfusions were noted (p = 0.003 and 0.005, respectively). Perioperative morbidity and mortality were statistically comparable in the two groups (p = 0.72 and 0.395, respectively). Postoperative 5 year survival in group 1 was 55%, in group 2 48% (log-rank p = 0.353). Five year recurrence-free survival in group 1 was 53%, in group 2 42% (log-rank p = 0.180). Diffuse metastasis occurred mostly in group 2, whereas in group 1 oligometastasis was more frequently noted. CONCLUSION: Postoperative outcome after salvage resection seems statistically comparable to results following curative resection after induction therapy. Diffuse distant metastasis is frequently noted. Careful patient selection is required.

[Videothoracoscopic Sympathetic Clipping in a Patient With Azygos Lobe. Intraoperative Management to Avoid Potential Complications]. / Videothorakoskopisches Sympathikus-Clipping bei einem Patienten mit Lobus venae azygos. Intraoperatives Management zur Vermeidung von potenziellen Komplikationen.

INTRODUCTION: Sympathetic clipping in the presence of an azygos lobe is a rare combination. Anatomical relations between the sympathetic trunk and the mesoazygos impede surgical handling and can be associated with potential complications. INDICATION: We report the case of a 25-year old woman with grade III palmoplantar and axillary hyperhidrosis with azygos lobe incidentally found on preoperative chest X-ray. METHOD: Our intraoperative video shows a step-by-step approach to the sympathetic trunk in the presence of the azygos lobe, involving thoracoscopic looping and precise clip application onto the sympathetic trunk. Video-assisted reposition and expansion of the accessory lobe to avoid potential complications have been demonstrated. CONCLUSION: Videothoracoscopic sympathetic clipping in patients with lobus azygos is technically challenging. Potential complications can be avoided by coordinated surgical management.

Long-Term Survival after Salvage Surgery for Local Failure after Definitive Chemoradiation Therapy for Locally Advanced Non-small Cell Lung Cancer.

BACKGROUND: The incidence of local failure and residual tumor after definitive chemoradiation therapy (dCRT) for locally advanced non-small-cell lung cancer remains high, irrespective of applied radiation dose (>59 Gy). So-called salvage surgery has been suggested as a feasible treatment option after failure of definitive chemoradiation for locally advanced non-small cell lung cancer (NSCLC). Experience with salvage lung surgery (SLS) is limited, and long-term survival is rarely reported. Patient selection criteria for surgical lung salvage are not defined. The aim of this study was to assess postoperative survival and perioperative morbidity/mortality to identify prognostic factors and to define patient selection criteria. PATIENTS AND METHODS: Records of 13 consecutive patients with locally advanced NSCLC, who underwent SLS at a single institution between March 2011 and November 2016, were reviewed. Descriptive statistics were applied for patient characteristics and surgical and oncological outcome. Survival rates were calculated using the Kaplan-Meier method and were compared with the long-rank test. RESULTS: All patients initially received curative-intent definitive chemoradiation with median radiation doses of 66 Gy (range 59.4-72) and concurrent platinum-based chemotherapy. Clinical tumor stage before definitive chemoradiation was IIIA in 9, IIIB in 3, IV in 1 patients. Median interval between definitive chemoradiation and salvage surgery was 6.7 months. Perioperative morbidity and 30-days-mortality was 38% and 7.7%, respectively. The median postoperative survival and estimated 5-year survival rate were 29.7 months and 46%, respectively. CONCLUSION: SLS in patients with locally advanced non-small cell lung surgery following dCRT is feasible, prolongs long-term survival and allows local tumor control. Selection criteria remain undefined and patients should be considered surgical candidates during multidisciplinary team conference.

Forty-Two Years' Experience with Pulmonary Resections of Metastases from Colorectal Cancer.

Background Pulmonary metastasectomy is a commonly performed surgery in patients with controlled metastatic colorectal cancer (CRC). We reviewed our long-term single institution experience with lung resections for colorectal metastases to assess the factors influencing patient survival. Materials and Methods A cohort of 220 patients (138 men and 82 women; median age, 59 years) who underwent complete pulmonary metastasectomy for CRC with curative intent between 1972 and 2014 was retrospectively analyzed. The impact of factors related to primary tumor, metastases, and associated therapy on patient survival was assessed. Results Two postoperative inhospital deaths occurred. The median interoperative interval was 26 months. The overall 5-year survival rate after pulmonary metastasectomy was 49.4%. In univariable analysis, bilateral pulmonary metastases (log rank p = 0.02), multiple metastases (log rank p = 0.005), and stage IV UICC (the International Union Against Cancer) CRC at the time of initial presentation (log rank p = 0.008) were significantly associated with poor outcome. Multivariable Cox analysis demonstrated that stage IV CRC (p = 0.02) and multiple metastases (p = 0.0019) were statistically significant predictors of survival after the pulmonary metastasectomy. There was no significant difference in survival between patients with high versus low preoperative carcinoembryonic antigen serum level (p = 0.149), high versus low preoperative carbohydrate antigen 19-9 serum level (p = 0.291), and primary tumor location in rectum versus colon (p = 0.845). Conclusion Patients with unilateral metastasis and stages I to III primary tumor benefited most from pulmonary metastasectomy for CRC.

Should salvage surgery be considered for local recurrence after definitive chemoradiation in locally advanced non-small cell lung cancer?

BACKGROUND: Incidence of local relapse after definitive chemoradiation (>59 Gy) for locally advanced non-small-cell lung cancer (NSCLC) is high, irrespective of high dose radiation applied. Experience with salvage lung resections in patients with locally relapsed NSCLC after definitive chemoradiation is limited. We present our series of salvage lung resections for local NSCLC relapse after curative-intent chemoradiation for locally advanced tumor. METHODS: Nine consecutive patients with local tumor recurrence or persistence following definitive chemoradiation were reviewed. Kaplan-Meier analysis was used to assess patient survival. RESULTS: All patients received definitive radiation (median dose 66.2 Gy) with concurrent chemotherapy. Tumor stage prior to chemoradiation was IIIA in 8 patients and IV in 1. In 4 patients tumor invaded the chest wall, in 2 the spine and in 1 the aorta. Median interval between chemoradiation and salvage resection was 30.2 weeks. Nine patients underwent 9 resections (6 lobectomies, 1 bilobectomy, 1 pneumonectomy and 1 bi-segmentectomy). One death occurred on the 12th postoperative day. Median overall survival was 23 months; postoperative 3-year survival was 47 %. Median progression-free survival was 21 months. CONCLUSION: Salvage lung resection for locally recurrent or persisted NSCLC in selected patients with locally advanced NSCLC following definitive chemoradiation is a worthwhile treatment option.

[Effect of free fatty acids on CYP19A1 (aromatase) gene expression in human adipose tissue stromal vascular fraction cells].

Aromatase plays an important role in the estrogen biosynthesis. Its gen (CYP19A1) is expressed in preadipocytes (stromal vascular fraction, SVF) of adipose tissue. Estrogens are found to be protective for metabolism homeostasis, and cardiovascular system. Disturbed dietary and endogenous fatty acids (FAs) turnover is responsible for development of metabolic syndrome and it complications. Aim of the work was to investigate the effect of physiological concentrations of acids: arachidonic (AA), oleic (OA), palmitynoic (PA) and eikozapentaenoic (EPA) on CYP19A1 expression in differentiating human SVF, able to form adipocytes as well as endothelial cells. Material and Methods: Human (n=38 healthy woman) SVF cells were isolated from subcutaneous adipose tissue harvested intrasurgery. SVF cells were incubated in proadipogenic or angiogenic media to obtain adipocytes (Adipo-SVF) or endothelial (Angio-SVF) cells (confirmed by microarray). Changes in the CYP19A1 expression induced by 24hs incubation in the presence of FAs (10 ­ 30 µM )were monitored by the Real time PCR (qRT -PCR). Results: The aromatase gene expression correlated positively with BMI of patients, but only in group of obese or overweight women. The negative correlation was found in the group of young, slim women. The highest expression of aromatase was found in the fresh, not differentiated SVF. In differentiating to endothelial cells (Angio - SVF) OA inhibited (p=0.008), when n-3 polyunsaturated AA activated (p=0.003) the CYP19A1 gene expression. In differentiating to preadipocytes (Adipo-SVF) AA significantly (p=0.031) inhibited CYP19A1 expression. Conclusion: The changes in the aromatase gene expression in differentiating SVF has been confirmed. The different effect of the dietary FA (OA vs. AA) on the aromatase gene expression argue for the role of the locally formed proangiogenic estrogens.

Combined Clagett procedure, negative pressure therapy, and thoracomyoplasty for treatment of late-onset postpneumonectomy empyema necessitatis.

Late-onset post-pneumonectomy empyema necessitatis can occur many years after the surgery and is a life-threatening condition. A 58-year-old male presented with empyema necessitatis 18 years after undergoing pneumonectomy. He was successfully treated with a modified two-stage Clagett procedure and ambulatory negative pressure as the bridge between the stages. The 72-month follow-up was uneventful. The complete obliteration of the rigid and wide residual postpneumonectomy cavity was necessary to avoid re-recurrence of the infection.

Is salvage surgery for recurrent non-small-cell lung cancer after definitive non-operative therapy associated with reasonable survival?

A best evidence topic in thoracic surgery was written according to a structured protocol. The question addressed was whether salvage pulmonary resection is possible and worthwhile for patients with recurrence of non-small-cell lung cancer (NSCLC) after prior definitive non-operative therapy. A total of nine reports were identified using the reported search, of which four represented the best available evidence to answer the clinical question. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results of these papers are tabulated. All studies were retrospective. In total, 48 pulmonary salvage resections were performed in 47 patients after prior definitive radiation, chemoradiation or stereotactic body radiation therapy, of which 28 were lobectomies (including 1 sleeve lobectomy), 12 pneumonectomies, 4 bilobectomies and 4 sublobar resections (2 segmentectomies and 2 wedge resections). Postoperative complications ranged from 0 to 58% (mean from four studies 42.5%). Only one study reported any mortality (4%), the other three had zero mortality. Median postoperative survival was reported in two studies and ranged from 9 to 30 months. Experience with salvage lung resection for locally recurrent NSCLC, after prior definitive non-surgical treatment, remains limited. Therefore, this analysis was based on only 48 resections in 47 patients from four retrospective studies. Nevertheless, the published data suggest that salvage lung surgery for recurrent, previously non-operatively managed non-small-cell lung cancer is a worthwhile treatment option with good survival, acceptable morbidity and low mortality.

Occupational exposure to diisocyanates in polyurethane foam factory workers.

OBJECTIVES: The aim of the study was to evaluate health effects of occupational exposure to diisocyanates (DIC) among polyurethane foam products factory workers. MATERIAL AND METHODS: Thirty workers had a physical examination, skin prick tests with common allergens, allergen-specific immunoglobulin E (IgE) antibodies to diisocyanates and pulmonary function tests. Concentrations of selected isocyanates in the workplace air samples as well as concentration of their metabolites in the urine samples collected from the workers of the plant were determined. RESULTS: The most frequent work-related symptoms reported by the examined subjects were rhinitis and skin symptoms. Sensitization to at least 1 common allergen was noted in 26.7% of the subjects. Spirometry changes of bronchial obstruction of a mild degree was observed in 5 workers. The specific IgE antibodies to toluene diisocyanate (TDI) and 4,4'-methylenebis(phenyl isocyanate) (MDI) were not detected in any of the patients' serum. Cellular profiles of the collected induced sputum (ISP) did not reveal any abnormalities. Air concentrations of TDI isomers ranged 0.2-58.9 µg/m3 and in 7 cases they exceeded the Combined Exposure Index (CEI) value for those compounds. Concentrations of TDI metabolites in post-shift urine samples were significantly higher than in the case of pre-shift urine samples and in 6 cases they exceeded the British Biological Monitoring Guidance Value (BMGV - 1 µmol amine/mol creatinine). We didn't find a correlation between urinary concentrations of TDI, concentrations in the air and concentrations of toluenediamine (TDA) in the post shift urine samples. Lack of such a correlation may be an effect of the respiratory protective equipment use. CONCLUSIONS: Determination of specific IgE in serum is not sensitive enough to serve as a biomarker. Estimation of concentrations of diisocyanate metabolites in urine samples and the presence of work-related allergic symptoms seem to be an adequate method for occupational exposure monitoring of DIC, which may help to determine workers at risk as well as to recognize hazardous workplaces.

SMARCB1(INI1)-deficient sinonasal basaloid carcinoma: a novel member of the expanding family of SMARCB1-deficient neoplasms.

Poorly differentiated sinonasal carcinomas are a heterogenous group of aggressive neoplasms that encompasses squamous cell carcinoma including basaloid variant, lymphoepithelial carcinoma, sinonasal undifferentiated carcinoma, and neuroendocrine-type small cell carcinoma. We herein describe 3 cases of a hitherto unreported variant combining features of basaloid carcinoma with variable intermingled rhabdoid cells. Patients were 2 women (aged 28 and 35) and a man (52 y) who presented with sinonasal masses. All had advanced local disease with bone involvement (pT4). None had a history of irradiation or a family history of rhabdoid tumors. Treatment was surgery and adjuvant chemoradiation. One patient developed liver, lung, pleural, and pericardial metastases (63 mo) and is currently (70 mo) alive under palliative treatment. Another developed recurrent cervical lymph node metastases and died of disease 8.5 years later. The youngest patient was disease-free at last follow-up 7 years later. Histologic features were very similar in all 3 cases and showed intimate admixture of compact basaloid cell nests with peripheral palisading, perivascular pseudorosettes, and a few scattered rhabdoid cells. Rhabdoid cells were more extensive in the metastasis in 1 case but formed a minor inconspicuous component in the primary tumors in all cases. Striking features common to all cases were (1) basaloid "blue" appearance at low power, (2) papilloma-like exophytic component, (3) extensive pagetoid surface growth with prominent denuding features, and (4) replacement of underlying mucous glands mimicking an inverted papilloma. Clear-cut origin from benign papilloma and overt squamous differentiation were lacking. Diffuse (2) or partial (1) p16 expression was noted, but all cases lacked human papillomavirus DNA by molecular tests. In situ hybridization was negative for Epstein-Barr virus. Immunohistochemistry showed diffuse expression of pancytokeratin. CK5 and vimentin showed intermingling of CK5/vimentin basaloid and CK5/vimentin rhabdoid cells. Complete loss of nuclear SMARCB1 expression was seen in all cases including also the denuding carcinoma in situ-like surface lesions. To our knowledge, this variant of sinonasal carcinoma has not been reported before. The identical features in all 3 cases suggest a specific disease rather than a nonspecific dedifferentiated phenotype. Awareness of this rare variant and thus reporting of additional cases is necessary for defining its full morphologic and biological spectrum.