Bronchial epithelial-myoepithelial carcinoma

Epithelial-myoepithelial tumor is extremely rare as a pulmonary neoplasm. Only 20 cases have been reported to date, of which 14 were malignant. We report a case of intrabronchial epithelial-myoepithelial carcinoma in a 73-year-old man with a history of heavy smoking. The tumor was well-circumscribed and caused distal airway obstruction. Histologically, the tumor showed glandular and solid architecture. The glands were composed of an inner layer of epithelial cells and an outer layer of myoepithelial cells. The solid areas consisted of spindle-shaped myoepithelial cells. Immunohistochemical staining was positive for p53 and c-Kit (CD117). Focal atypia and increased mitotic activity were present, but no vascular invasion or nodal metastasis was identified.     

Functional evidence of decreased tumorigenicity associated with monochromosome transfer of chromosome 14 in esophageal cancer and the mapping of tumor-suppressive regions to 14q32

Despite the abundant evidence of high allelic loss of chromosome arm 14q in human cancers, tumor-suppressor genes mapped to this chromosome have yet to be identified. To narrow the search for candidate genes, we performed monochromosome transfer of chromosome 14 into an esophageal carcinoma cell line, SLMT-1 S1. Statistically significant suppression of the tumorigenic potential of microcell hybrids containing the transferred chromosome 14 provided functional evidence that tumor-suppressive regions of chromosome 14 are essential for esophageal cancer. Tumor segregants emerging in nude mice during the tumorigenicity assay were analyzed by detailed PCR-microsatellite typing to identify critical nonrandomly eliminated regions (CRs). A 680-kb CR mapped to 14q32.13 and an approximately 2.2-Mb CR mapped to 14q32.33 were delineated. Dual-color BAC FISH analysis of microcell hybrids and tumor segregants verified the selective loss of the 14q32.13 region. In contrast, similar transfers of an intact chromosome 11 into SLMT-1 S1 did not significantly suppress tumor formation. These functional complementation studies showing the correlation of tumorigenic potential with critical regions of chromosome 14 validated the importance of the 14q32 region in tumor suppression in esophageal cancer. The present study also paved the path for further identification of novel tumor-suppressor genes that are relevant to the molecular pathogenesis of esophageal cancer.     

High-performance liquid chromatographic method for quantification of busulfan in plasma after derivatization by tetrafluorothiophenol

A high-performance liquid chromatographic (HPLC) method was developed and validated for the determination of busulfan in plasma. Busulfan was extracted in toluene, derivatized by 2,3,5,6-tetrafluorothiophenol to obtain di-TFTP-butane, the derivatization product was then re-extracted in toluene and injected into the HPLC system with ultraviolet detection (wavelength: 275 nm). Recovery from extraction was 80%, the limit of quantification was 50 ng/ml and linearity ranged from 50 to 2000 ng/ml. In addition, forty-two samples obtained from pediatric patients treated with busulfan were analyzed by the HPLC and GC-MS assays based on the same derivatization procedure. The correlation between the di-TFTP-butane concentrations was highly significant (p<0.0001), demonstrating that the two methods were in good agreement.     

Clinical utility of the AJCC 8th edition pT1 subclassification and impact on practice patterns in stage I seminoma

BackgroundThe American Joint Committee on Cancer 8^th edition staging guidelines for testicular cancer established a 3 cm cutoff to subclassify stage T1 seminomas (<3 cm = pT1a and ≥3 cm = pT1b). The efficacy of this cutoff in predicting metastatic disease and impact on treatment patterns have not been studied.MethodsWe retrospectively reviewed patients with pT1 testicular seminoma in the National Cancer Database from 2004 to 2016. Receiver operating curves were used to determine the efficacy of the 3 cm tumor cutoff in identifying metastatic disease, and multivariable regression was used to compute the effect of tumor size on the rate of adjuvant therapy among Stage I patients.ResultsA total of 10,134 patients with pT1 seminoma were evaluated. The current size cutoff of 3 cm for subclassification did not exhibit high discrimination in identifying metastatic disease (area under receiver operating curve: 0.546). Surveillance has grown as the preferred treatment after orchiectomy ?32.1% in 2004 to 81.2% in 2015. However, the rate of adjuvant therapy for pT1, Stage I seminomas associated positively with tumor size even with adjustment for year of diagnosis. For tumors above 3 cm, the odds ratio stabilized around 1.9. By using the 3 cm cutoff to guide adjuvant therapy, up to 85% of T1b patients may be overtreated.ConclusionThe 3 cm cutoff for subclassification of Stage I seminoma does not predict metastatic recurrence but is associated with increased receipt of adjuvant therapy. A 3 cm cutoff and the pT1a/b classification may therefore contribute to overtreatment in many young patients with a long life expectancy for whom minimizing adverse effects should be prioritized.     

Efficacy and tolerability of anti-asthma herbal medicine intervention in adult patients with moderate-severe allergic asthma

BACKGROUND: Chinese herbal medicine has a long history of human use. A novel herbal formula, anti-asthma herbal medicine intervention (ASHMI), has been shown to be an effective therapy in a murine model of allergic asthma. OBJECTIVE: This study was undertaken to compare the efficacy, safety, and immunomodulatory effects of ASHMI treatment in patients with moderate-severe, persistent asthma with prednisone therapy. METHODS: In a double-blind trial, 91 subjects underwent randomization. Forty-five subjects received oral ASHMI capsules and prednisone placebo tablets (ASHMI group) and 46 subjects received oral prednisone tablets and ASHMI placebo capsules (prednisone group) for 4 weeks. Spirometry measurements; symptom scores; side effects; and serum cortisol, cytokine, and IgE levels were evaluated before and after treatment. RESULTS: Posttreatment lung function was significantly improved in both groups as shown by increased FEV(1) and peak expiratory flow findings (P<.001). The improvement was slightly but significantly greater in the prednisone group (P<.05). Clinical symptom scores, use of beta(2)-bronchodilators, and serum IgE levels were reduced significantly, and to a similar degree in both groups (P<.001). T(H)2 cytokine levels were significantly reduced in both treated groups (P<.001) and were lower in the prednisone-treated group (P<.05). Serum IFN-gamma and cortisol levels were significantly decreased in the prednisone group (P<.001) but significantly increased in the ASHMI group (P<.001). No severe side effects were observed in either group. CONCLUSION: Anti-asthma herbal medicine intervention appears to be a safe and effective alternative medicine for treating asthma. In contrast with prednisone, ASHMI had no adverse effect on adrenal function and had a beneficial effect on T(H)1 and T(H)2 balance.     

Mutational analysis of the PTEN/MMAC1 gene in primary oesophageal squamous cell carcinomas.

AIM: To investigate whether PTEN/MMAC1 mutations play a role in the carcinogenesis of oesophageal squamous cell carcinoma. METHODS: A panel of 33 primary oesophageal squamous cell carcinoma tumour samples and 20 corresponding morphologically normal tissues was examined for mutations in all nine exons of the PTEN/MMAC1 gene by means of polymerase chain reaction single strand conformational polymorphism analysis (PCR-SSCP) and direct DNA sequencing methods. RESULTS: Only one of 33 oesophageal squamous cell carcinomas showed an aberrant SSCP band. Further sequencing analysis of this sample revealed an 802 -29 T-->C substitution in intron 7. PTEN/MMAC1 mutations were not found in the mutational "hot spot" in exon 5, even after direct sequencing of six oesophageal squamous cell carcinoma samples and three normal tissues. However, a deletion of one nucleotide T at position 492 +8 in intron 5 was seen in all samples. CONCLUSION: These results suggest that PTEN/MMAC1 mutations do not play a major role in the carcinogenesis of oesophageal squamous cell carcinoma.     

Myocardial infarction complicating gastrointestinal hemorrhage

OBJECTIVE: To determine the frequency of and risk factors for myocardial infarction (MI) in patients admitted to an intensive-care unit (ICU) with gastrointestinal (GI) hemorrhage and to ascertain the effects on mortality and lengths of stay. MATERIAL AND METHODS: Demographic, laboratory, and outcome data were determined for all patients admitted to a medical ICU with GI hemorrhage between April 1996 and January 1997. Serial creatine kinase with isoenzyme levels and electrocardiograms were interpreted blindly by a senior cardiologist. RESULTS: For 83 consecutive admissions to the ICU because of GI hemorrhage, the patients' mean (+/- standard error) age was 65.0 +/- 1.7 years and APACHE II (acute physiology and chronic health evaluation) score was 15.7 +/- 0.8. In-hospital death occurred in 16 patients (19%). Patients who did not survive had a lower admission systolic blood pressure (99.2 +/- 4.5 versus 115.0 +/- 4.0 mm Hg; P = 0.01) than did those who survived. Eleven of 83 patients (13%) fulfilled both enzymatic and electrocardiographic criteria for MI. Ten patients (12%) had electrocardiographic evidence of myocardial ischemia but did not meet criteria for MI. Patients with MI were older (74.4 +/- 4.0 versus 61.7 +/- 2.0 years; P < 0.05), had a higher acuity of illness (APACHE II score, 21.6 +/- 3.0 versus 14.6 +/- 0.7; P < 0.05), and had more coronary risk factors (2.3 +/- 0.3 versus 1.4 +/- 0.1; P < 0.05) in comparison with those without MI or ischemia. Patients with MI also had longer ICU (8.6 +/- 2.4 versus 3.3 +/- 0.4 days; P < 0.05) and hospital (16.3 +/- 3.4 versus 9.1 +/- 0.8 days; P < 0.05) lengths of stay. Patients older than 65 years had a threefold increased risk (risk ratio, 4.0; 95% confidence interval, 0.9 to 17.4) and those with two or more risk factors for coronary artery disease had a ninefold increased risk of MI (risk ratio, 10.2; 95% confidence interval, 1.4 to 76.1) in comparison with those who were younger or who had fewer coronary risk factors, respectively. MI complicating GI hemorrhage did not significantly affect the risk of in-hospital mortality (risk ratio, 1.5; 95% confidence interval, 0.5 to 4.4). CONCLUSION: MI occurs frequently in patients with GI hemorrhage admitted to an ICU. Age more than 65 years and two or more risk factors for coronary artery disease identify patients who are at greatest risk for occurrence of MI, which is associated with longer ICU and hospital stays.