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Purpose: Local and distant failure rates remain high despite aggressive chemoradiation (CRT) treatment for Stage III non-small-cell lung cancer. We conducted preclinical studies of docetaxel's cytotoxic and radiosensitizing effects on lung cancer cell lines and designed a pilot study to target distant micrometastasis upfront with one-cycle induction chemotherapy, followed by low-dose radiosensitizing docetaxel CRT.Methods and Materials: A preclinical study was conducted in human lung cancer cell lines NCI 520 and A549. Cells were treated with two concentrations of docetaxel for 3 h and then irradiated immediately or after a 24-h delay. A clonogenic survival assay was conducted and analyzed for cytotoxic effects vs. radiosensitizing effects of docetaxel. A pilot clinical study was designed based on preclinical study findings. Twenty-two patients were enrolled with a median follow-up of 4 years. Induction chemotherapy consisted of 75 mg/m(2) of docetaxel and 75 mg/m(2) of cisplatin on Day 1 and 150 mg/m(2) of recombinant human granulocyte colony-stimulating factor on Days 2 through 10. Concurrent CRT was started 3 to 6 weeks later with twice-weekly docetaxel at 10 to 12 mg/m(2) and daily delayed radiation in 1.8-Gy fractions to 64.5 Gy for gross disease.Results: The preclinical study showed potent cytotoxic effects of docetaxel and subadditive radiosensitizing effects. Delaying radiation resulted in more cancer cell death. The pilot clinical study resulted in a median survival of 32.6 months for the entire cohort, with 3- and 5-year survival rates of 50% and 19%, respectively, and a distant metastasis-free survival rate of 61% for both 3 and 5 years. A pattern-of-failure analysis showed 75% chest failures and 36% all-distant failures. Therapy was well tolerated with Grade 3 esophagitis observed in 23% of patients.Conclusions: One-cycle full-dose docetaxel/cisplatin induction chemotherapy with recombinant human granulocyte colony-stimulating factor followed by pulsed low-dose docetaxel CRT is promising with regard to its antitumor activity, low rates of distant failure, and low toxicity, suggesting that this regimen deserves further investigation. [ABSTRACT FROM AUTHOR]

Purpose: We report the toxicity profile and pharmacokinetic data of a schedule-dependent chemoradiation regimen using pulsed low-dose paclitaxel for radiosensitization in a Phase I study for inoperable non-small-cell lung cancer.Methods and Materials: Paclitaxel at escalating doses of 15 mg/m(2), 20 mg/m(2), and 25 mg/m(2) were infused on Monday, Wednesday, and Friday with daily chest radiation in cohorts of 6 patients. Daily radiation was delayed for maximal G2/M arrest and apoptotic effect, an observation from preclinical investigations. Plasma paclitaxel concentration was determined by high-performance liquid chromatography.Results: Dose-limiting toxicities included 3 of 18 patients with Grade 3 pneumonitis and 3 of 18 patients with Grade 3 esophagitis. There was no Grade 4 or 5 pneumonitis or esophagitis. There was also no Grade 3 or 4 neutropenia, thrombocytopenia, anemia or neuropathy. For Dose Levels I (15 mg/m(2)), II (20 mg/m(2)), and III (25 mg/m(2)), the mean peak plasma level was 0.23 +/- 0.06 micromol/l, 0.32 +/- 0.05 micromol/l, and 0.52 +/- 0.14 micromol/l, respectively; AUC was 0.44 +/- 0.09 micromol/l, 0.61 +/- 0.1 micromol/l, and 0.96 +/- 0.23 micromol/l, respectively; and duration of drug concentration >0.05 micromol/l (t > 0.05 micromol/l) was 1.6 +/- 0.3 h, 1.9 +/- 0.2 h, and 3.0 +/- 0.9 h, respectively.Conclusion: Pulsed low-dose paclitaxel chemoradiation is associated with low toxicity. Pharmacokinetic data showed that plasma paclitaxel concentration >0.05 micromol/l for a minimum of 1.6 h was sufficient for effective radiosensitization. [ABSTRACT FROM AUTHOR]

BACKGROUND Castleman disease was first described in 1956 as mediastinal masses composed of benign lymphoid hyperplasia with germinal center formation and capillary proliferation closely resembling thymomas. It has been linked with many multi-system disorders, including myasthenia gravis. Cases of Castleman disease with corresponding myasthenia gravis have higher rates of postoperative myasthenic crisis, which are reported as high as 37.5%. We encountered a case of Castleman disease with myasthenia gravis that was discovered early and managed successfully with complete surgical resection and no postoperative myasthenic crisis. CASE REPORT A 25-year-old woman with an uncomplicated history presented with shortness of breath, numbness in hands, tiring with chewing, and fatigue. Myasthenia gravis was diagnosed with serology test results, and a 7.5×7.0-cm mediastinal mass was discovered in addition to the incidental finding of a persistent left superior vena cava, closely abutting the mass. Biopsy showed lymphoid proliferation, regressed germinal centers surrounded by small lymphocytes, and vascular proliferation, consistent with unicentric Castleman disease, hyaline-vascular type. The patient was successfully treated for Castleman disease with myasthenia gravis, and no postoperative myasthenic crisis occurred. CONCLUSIONS Castleman disease associated with myasthenia gravis can dramatically increase the risk of postoperative myasthenic crisis. Our literature review of all 16 cases of Castleman disease with myasthenia gravis since 1973 revealed that 18.75% of cases were associated with a postoperative myasthenic crisis. This association elicits the importance of prompt diagnosis of myasthenia gravis when evaluating mediastinal masses and the value of having neurology and anesthesiology staff aware of the increased risk of crisis.

Short-term extracorporeal membrane oxygenation is a useful adjunct to thoracic procedures. We report the cases of 2 middle-aged men who were supported with venovenous extracorporeal membrane oxygenation to facilitate tumor debulking and recanalization of the carina and mainstem bronchi. Neither patient had major complications or adverse events. These cases suggest that short-term extracorporeal membrane oxygenation is safe in patients undergoing complex resection or debulking of endobronchial lesions., (© 2021 by the Texas Heart® Institute, Houston.)

Rationale: Less invasive, nonsurgical approaches are needed to treat severe emphysema. Objectives: To evaluate the effectiveness and safety of the Spiration Valve System (SVS) versus optimal medical management. Methods: In this multicenter, open-label, randomized, controlled trial, subjects aged 40 years or older with severe, heterogeneous emphysema were randomized 2:1 to SVS with medical management (treatment) or medical management alone (control). Measurements and Main Results: The primary efficacy outcome was the difference in mean FEV 1 from baseline to 6 months. Secondary effectiveness outcomes included: difference in FEV 1 responder rates, target lobe volume reduction, hyperinflation, health status, dyspnea, and exercise capacity. The primary safety outcome was the incidence of composite thoracic serious adverse events. All analyses were conducted by determining the 95% Bayesian credible intervals (BCIs) for the difference between treatment and control arms. Between October 2013 and May 2017, 172 participants (53.5% male; mean age, 67.4 yr) were randomized to treatment ( n  = 113) or control ( n  = 59). Mean FEV 1 showed statistically significant improvements between the treatment and control groups-between-group difference at 6 and 12 months, respectively, of 0.101 L (95% BCI, 0.060-0.141) and 0.099 L (95% BCI, 0.048-0.151). At 6 months, the treatment group had statistically significant improvements in all secondary endpoints except 6-minute-walk distance. Composite thoracic serious adverse event incidence through 6 months was greater in the treatment group (31.0% vs. 11.9%), primarily due to a 12.4% incidence of serious pneumothorax. Conclusions: In patients with severe heterogeneous emphysema, the SVS shows significant improvement in multiple efficacy outcomes, with an acceptable safety profile.Clinical trial registered with www.clinicaltrials.gov (NCT01812447).

Thoracic surgeons traditionally have measured their outcomes in terms of mortality, complication rates, recurrence patterns, and long-term survival for their cancer patients. These metrics of quality continue to be important today, but increasingly surgeons are under scrutiny for resource utilization, patient experience, and cost effectiveness. Intelligent decisions about resource use require knowledge of utility, disutility, and cost -- information that is still limited and not easily implemented at the time treatment decisions are made. If we accept the proposition that lung cancer care requires a multidisciplinary team making best use of available resources to minimize unwarranted variation, maximize outcomes, and control costs, then three critical needs can be identified: consensus on goals, robust data, and alignment of incentives across disciplines., (© 2014 Wiley Periodicals, Inc.)

Disinfection by-products (DBPs) arise when natural organic matter in source water reacts with disinfectants used in the water treatment process. Studies have suggested an association between DBPs and birth defects. Neural tube defects (NTDs) in embryos of untreated control mice were first observed in-house in May 2006 and have continued to date. The source of the NTD-inducing agent was previously determined to be a component of drinking water. Tap water samples from a variety of sources were analyzed for trihalomethanes (THMs) to determine if they were causing the malformations. NTDs were observed in CD-1 mice provided with treated and untreated surface water. Occurrence of NTDs varied by water source and treatment regimens. THMs were detected in tap water derived from surface water but not detected in tap water derived from a groundwater source. THMs were absent in untreated river water and laboratory purified waters, yet the percentage of NTDs in untreated river water were similar to the treated water counterpart. These findings indicate that THMs were not the primary cause of NTDs in the mice since the occurrence of NTDs was unrelated to drinking water disinfection.

The removal of fluoride using red mud has been improved by acidifying red mud with hydrochloric, nitric and sulphuric acid. The acidification of red mud causes sodalite and cancrinite phases to dissociate, confirmed by the release of sodium and aluminium into solution as well as the disappearance of sodalite bands and peaks in infrared and X-ray diffraction data. The dissolution of these mineral phases increases the amount of available iron and aluminium oxide/hydroxide sites that are accessible for the adsorption of fluoride. However, concentrated acids have a negative effect on adsorption due to the dissolution of these iron and aluminium oxide/hydroxide sites. The removal of fluoride is dependent on the charge of iron and aluminium oxide/hydroxides on the surface of red mud. Acidifying red mud with hydrochloric, nitric and sulphuric acid resulted in surface sites of the form ≡SOH2(+) and ≡SOH. Optimum removal is obtained when the majority of surface sites are in the form ≡SOH2(+) as the substitution of a fluoride ion does not cause a significant increase in pH. This investigation shows the importance of having a low and consistent pH for the removal of fluoride from aqueous solutions using red mud., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Purpose: To determine the national surgical practice patterns of care for operable lung cancer patients treated with radiation., Materials and Methods: A nationwide survey of a stratified random sample of institutions was conducted for patients who had non-metastatic lung cancer, Karnofsky Performance Scores (KPS) > or =60, and who had received radiation therapy as definitive or adjuvant treatment. Among 541 patients, representing a weighted sample size of 42,335 patients nationwide, 131 (19.8%) underwent surgery as part of their therapy. Pearson chi statistics were used to analyze characteristics of this subset of patients., Results: Of the 131 patients who underwent surgery, 126 patients who had non-small cell lung cancer (NSCLC) were analyzed. Surgical patients were younger, had less weight loss, higher KPS, and higher forced expiratory volume within 1 second (FEV1) values than those treated without surgery. Surgical patients had more stage I/II (53.5% vs 32.2%; p = 0.0004) and less clinical N2/N3 disease (28.8% vs 47.5%; p = 0.002) than nonsurgical patients. Surgery consisted of lobectomy or bilobectomy in 63.2% of patients, pneumonectomy in 23.5%, and wedge resection in 5.9%. Of the patients, 80.4% received radiation in the adjuvant setting and 9.9% in the neoadjuvant setting., Conclusions: Patients with non-metastatic lung cancer who are treated surgically and with radiation have clinically less advanced disease than those treated with radiation alone. Most radiation therapy in this setting is administrated postoperatively and secondary to hilar and/or mediastinal nodal involvement undetected before surgery. Improved preoperative nodal staging and neoadjuvant approaches may alter these practice patterns.

Purpose: To determine the overall survival, progression-free survival, and toxicity associated with concurrent paclitaxel/carboplatin and thoracic radiotherapy for completely resected patients with stage II and IIIA non-small-cell lung cancer (NSCLC)., Patients and Methods: Eighty-eight eligible patients had surgical resection for pathologic stage II or IIIA disease and received postoperative paclitaxel and carboplatin. Concurrent thoracic radiotherapy at 50.4 Gy in 28 fractions for 6 weeks (1.8 Gy/d, 5 days/wk) was given during cycles 1 and 2. A boost of 10.8 Gy in six fractions was given for extracapsular nodal extension or T3 lesions., Results: Treatment compliance was acceptable, with 93% compliance for radiation therapy and 86% for chemotherapy completion. The median duration of follow-up was 56.7 months (range, 17 to 61 months). The median overall survival time was 56.3 months, with 1-, 2-, and 3-year survival rates of 86%, 70%, and 61%, respectively. The 1-, 2-, and 3- year progression-free survival rates were 70%, 57%, and 50%, respectively. Brain metastasis occurred as the sole site of first failure in 11%, and 9% failed in other metastatic sites as first failure. Of the 43 patients who died, the cause of death was the treated cancer in 31 (35%). Local failure was a component of first failure in 15% of patients. Toxicities were acceptable. An overall survival comparison to Eastern Cooperative Oncology Group 3590 is favorable., Conclusion: The mature results of this trial suggest an improved overall and progression-free survival in this group of resected NSCLC patients, compared with previously reported trials. A phase III trial comparing this treatment regimen with standard therapy seems warranted.

Purpose: To compare the outcome of treatment of mediastinoscopy-verified N2 non-small-cell lung cancer treated with induction chemotherapy followed by either surgery or radiotherapy (RT), with both options followed by consolidation chemotherapy., Methods and Materials: A randomized Phase III trial for Stage IIIA (T1-T3N2M0) non-small cell lung cancer was conducted by the Radiation Therapy Oncology Group (RTOG) and Eastern Cooperative Oncology Group between April 1990 and April 1994. After documentation of N2 disease by mediastinoscopy or anterior mediastinotomy, patients received induction chemotherapy with cisplatin, vinblastine, and mitomycin-C. Mitomycin-C was later dropped from the induction regimen. Patients were then randomized to surgery or RT (64 Gy in 7 weeks) followed by cisplatin and vinblastine., Results: RTOG 89-01 accrued 75 patients, of whom 73 were eligible and analyzable. Twelve patients received induction chemotherapy but were not randomized to RT or surgery thereafter. Forty-five patients were randomized to postinduction RT or surgery. Of the analyzable patients, 90% had a Karnofsky performance score of 90-100, 18% had weight loss >5%, 37% had squamous cell histologic features, and 54% had bulky N2 disease. The distribution of bulky N2 disease was uniform among the treatment arms. The incidence of Grade 4 toxicity was 56% in patients receiving mitomycin-C and 29% in those who did not. Only 1 patient in each group had acute nonhematologic toxicity greater than Grade 3 (nausea and vomiting). No acute Grade 4 radiation toxicity developed. The incidences of long-term toxicity were equivalent across the arms. Three treatment-related deaths occurred: 2 patients in the surgical arms (one late pulmonary toxicity and one pulmonary embolus), and 1 patient in the radiation arm (radiation pneumonitis). Induction chemotherapy was completed in 78% of the patients. Complete resection was performed in 73% of 26 patients undergoing thoracotomy. Consolidation chemotherapy was completed in 75% of the patients. No statistically significant difference was found among the treatment arms. The overall progression-free survival rate was 53% at 1 year and 17% at 3 years. The median progression-free survival was 14 months. No difference in the 1-year survival rate (70% vs. 66%) or median survival time (19.4 vs. 17.4 months) between the surgery and RT arms. The median survival in the patients receiving induction chemotherapy only was 8.9 months. Mitomycin-C had no impact on survival (p = 0.75). No statistically significant difference was noted in the time to local failure between the surgical and RT arms., Conclusion: The patient accrual to this trial made its results inconclusive, but several observations are notable. In this trial, histologic confirmation of N2 disease in the surgical and nonsurgical arms eliminated the usual biases from clinical staging. In this setting, local control and survival were essentially equal between the surgical and RT arms. The 3- and 5-year survival rates of nonsurgical therapy were comparable to published surgical trials of N2 disease.

Chylothorax is an unusual complication of surgical procedures within the chest. Early recognition is important so that appropriate conservative measures can be applied. Operative intervention after a short course of supportive therapy will control most chyle fistulas. Methods of diagnosis in the postoperative setting and literature supporting various treatment options are the focus of this article.

Purpose: To assess frequency and significance of enlarged nonpalpable supraclavicular lymph nodes by using chest computed tomography (CT) and supraclavicular ultrasonography (US) in patients at initial diagnosis of lung cancer., Materials and Methods: Fifty-five patients with no prior malignancy who presented with suspected and subsequently proven lung cancer of any stage or a proven but potentially resectable lung cancer were prospectively selected after chest CT. Chest CT and other radiologic findings were reviewed and tabulated. Standardized US technique was used to identify and guide needle biopsy of enlarged supraclavicular lymph nodes (> or =0.5 cm short axis)., Results: Twenty-two (40%) of 55 patients had supraclavicular abnormalities detected at CT and/or US. In 18 (82%) of the 22 patients, supraclavicular abnormalities were recognizable at CT. Seventeen of 22 patients had malignant nodes, and five patients had benign nodes (n = 3), a cyst (n = 1), or an indeterminate lesion (n = 1) at US-guided supraclavicular needle sampling. There were no complications. Supraclavicular metastases (31% of patients) were about as common as the combined number of patients with indeterminate (n = 13) and probably or proven malignant (n = 6) adrenal nodules (35% of patients). Supraclavicular metastases were often associated with mediastinal adenopathy or suspected extrapulmonary nonnodal metastases (P <.05)., Conclusion: In many patients with lung cancer, chest CT that includes the neck base followed by US-guided sampling of enlarged supraclavicular lymph nodes is a simple and safe method for simultaneously establishing a tissue diagnosis and tumor nonresectability.

Background: Postoperative air leaks are a major cause of morbidity after lung resections. This study was designed to evaluate the efficacy and safety of a new synthetic, bioresorbable surgical sealant in preventing air leaks after pulmonary resection., Methods: In a multicenter trial, 172 patients undergoing thoracotomy were randomized intraoperatively in a 2:1 ratio to receive surgical sealant applied to sites at risk for air leak after standard methods of lung closure (treatment group) or to have standard lung closure only (control group). The primary outcome variable was the percentage of patients free of air leakage throughout hospitalization. Secondary outcome variables were the control of air leaks intraoperatively and the time to postoperative air leak cessation. Time to chest tube removal, time to hospital discharge, and safety outcomes were also evaluated., Results: Air leaks were identified before randomization in 89 of 117 patients in the treatment group and in 39 of 55 patients in the control group. Application of the sealant resulted in control of air leaks in 92% of treated patients (p < or = 0.001). A significantly higher percentage of treated patients than control patients remained free of air leaks during hospitalization (39% versus 11%, p < or =0.001). The mean times to last observable air leak were 30.9 hours in the treatment group and 52.3 hours in the control group (p = 0.006). In the treatment group, trends were observed for reduced time to chest tube removal and earlier discharge. No significant difference was identified in postoperative morbidity and mortality between the two groups., Conclusions: Air leaks after lung resection occur in most patients. The application of this novel surgical sealant appears to be effective and safe in preventing postoperative air leaks.

Background: Palliation of malignant dysphagia can be achieved by insertion of an endoprosthesis. Recently, metallic self-expanding prostheses have been introduced that offer the advantage of a lower complication rate over their plastic counterpart., Methods: Thirteen patients with dysphagia due to inoperable carcinoma of the esophagus were treated with coated Wallstent (Schneider (USA) Inc, Minneapolis, MN) endoprostheses, which were placed under fluoroscopic control. All patients were given general anesthesia during the procedure., Results: After successful insertion of all endoprostheses, the dysphagia of 12 of the patients improved while in the hospital. Average length of stay was 4.4 days. Two patients required a second stent because of migration or tumor overgrowth. Seven patients died with a mean survival of 54 days (range, 14 to 144 days), and 6 are alive a mean of 112 days (range, 32 to 263 days) after treatment., Conclusions: Coated Wallstent insertion is an effective, single treatment that quickly improves the patients' quality of life. Its effect on survival is yet to be established when used as a last resort in patients with inoperable esophageal carcinoma and poor general condition.

Four patients with chronic empyema after pneumonectomy have undergone successful obliteration of the empyema tract with a deepithelialized transverse rectus abdominis myocutaneous flap. The deepithelialized skin island has provided sufficient bulk for tract obliteration. Rotation of the skin island into the long axis of the rectus muscle has added considerable length to this flap, allowing it to reach the apex of the thoracic cavity. A recurrent loculation developed 4 months after the obliteration procedure in one patient. This was successfully treated with open pleural drainage and a second Clagett procedure. Over a mean follow-up period of 35 months, all four patients are free of further infectious sequelae. Chest roentgenograms have confirmed eradication of the tracts in all four patients.

The management of chylothorax requires a thorough understanding of the anatomy and pathophysiology of the major thoracic lymphatics, prompt diagnosis, and (with rare exception) conservative management, including evacuation of the pleural space, nutritional support, and measures to reduce chyle production. A minority of chylothoraces will fail to resolve with these measures. Surgical intervention is then required to prevent chronic metabolic deterioration and death.

A 41-year-old woman with recurrent attacks of postprandial abdominal pain was found on endoscopic retrograde cholangiopancreatography and subsequent computed tomographic scan to have an enteric duplication within the substance of the pancreas with communication to the pancreatic duct. Celiotomy demonstrated a noncontiguous gastric duplication cyst. Internal drainage was curative.