Histologic Diversity of Thymic Epithelial Tumors in Patients with Myasthenia Gravis

Background and Objective: Thymic epithelial tumors (TETs) include thymic carcinomas and thymomas, the latter of which can be further categorized by the World Health Organization (WHO) histologic classification based on the morphology of epithelial cells and the ratio of lymphocyte to epithelial cells (WHO types A, AB, B1, B2, and B3). TETs are rare malignancies with an incidence of 0.15 per 100,000 person-years in the United States. While their etiologies remain unknown, these tumors are associated with distinctly high rates of autoimmune disorders and paraneoplastic syndromes. The most common comorbid autoimmune disorder is myasthenia gravis (MG), affecting approximately 30% of patients with thymoma; thus, evaluating the risk of MG in patients with TETs of various histologies is important clinically. For the present retrospective study, we created a database of patients with TETs and examined prevalence of each histologic subtype in patients with MG. Methods: Drs. Patrick Loehrer, Kenneth Kesler, and colleagues have collaborated at the Indiana University Simon Cancer Center to care for over 1000 patients with TETs. The electronic health records of these patients were accessed via Cerner and used to input demographic, diagnostic, and histologic data into a REDCap database. The TETs were further categorized by WHO classification, and heterogenous tumors were categorized by their most aggressive histologic type (i.e. mixed type B2 and B3 categorized as B3). Results: Of 1023 total patients in the REDCap database, 626 were found to have sufficient documented information regarding TET diagnosis and histology as well as the presence or absence of MG (thymoma – 468; thymic carcinoma – 158). 112 of these patients carried diagnoses of both MG and a TET confirmed by pathology report (thymoma – 110; thymic carcinoma – 2). 77 (68.75%) patients were diagnosed with MG prior to TET, while 30 (26.79%) were diagnosed with MG after TET (p < 0.0001). The greatest prevalence of WHO histologic type in patients with thymoma and MG was Type B3 (36, 32.14%), followed by Type B2 (33, 29.46%), Type B1 (19, 16.96%), Type A (7, 6.25%), and Type AB (7, 6.25%) (X2 = 37.41, p < 0.0001). Notably, only 2 of 158 (1.27%) total patients with TC had comorbid MG in contrast to 110 of 468 (23.50%) with thymoma and MG; this suggests a uniquely favorable microenvironment of thymoma in patients with MG. Clinical Impact and Implications: A distinct link exists between myasthenia gravis and thymoma, particularly those of more aggressive WHO histologic types (Type B3 and Type B2). Future work will aim to determine whether histologic classification has a predictive value for tumor prognosis in patients with and without MG. Furthermore, patterns of gene expression associated with thymoma in patients with and without MG may elucidate the etiologic mechanisms for the development of this autoimmune disorder

Trends in Metastases among Patients with Masaoka-Koga Stage IV Thymic Epithelial Tumors

Background: Thymic epithelial tumors (TET’s), including thymomas (5 histological subtypes) and thymic carcinomas, are rare tumors with an estimated incidence of 0.15 per 100,000 person-years in the United States. While their etiologies remain largely unknown, some are associated with uniquely high rates of paraneoplastic syndromes and an elevated risk of secondary malignancies. And, though thymomas were once thought to be benign tumors, it is now well-documented that all TET\u27s can metastasize. The gold-standard in TET staging, the Masaoka-Koga system, defines metastatic disease as Stage IV, further specifying pleural/pericardial metastases as Stage IVa and lymphatic/hematogenous metastases as IVb. Unfortunately, little is known about patient prognosis as it relates to metastasis location. Here, we assemble and analyze one of the largest single-institution databases of TET patients in the world and seek to examine trends in metastases and their correlation with patient prognosis. Methods: Files of 1023 TET patients seen at Indiana University Hospital were accessed via Cerner, after which a standardized information list including demographics, diagnostics, tumor histology, treatments used, disease course, and patient outcome at last follow-up was extracted and input into a RedCap database. Results: Stage IV disease cases were filtered, yielding a total of 428 patients. Of these patients, 122 (29%) had carcinoma, making carcinoma the single largest histology represented in Stage IV. Locations of metastases also varied, with 284 patients (66%) having pleural metastases, 171 (40%) having lung, 71 (17%) liver, 58 (14%) bone, 56 (13%) pericardium, 37 (9%) neck lymph nodes, 12 (3%) brain, and 5 (1%) kidney. Moreover, 98 (23%) patients presented in stage IVb without any pleural/pericardial metastases. At last follow-up, 10% (19) of Stage IVa patients had no recurrence compared to only 3% (7) of IVb patients. Potential Impact: These data altogether suggest that disease spread outside the thorax occurs much more commonly than previously reported, and that rates of metastasis vary with tumor histology. Future analysis will elucidate the exact differences in the patterns of spread among histological types, how these patterns correlate with prognosis

Ruthenium polypyridyl complexes and their modes of interaction with DNA : is there a correlation between these interactions and the antitumor activity of the compounds?

Various interaction modes between a group of six ruthenium polypyridyl complexes and DNA have been studied using a number of spectroscopic techniques. Five mononuclear species were selected with formula [Ru(tpy) L1L2](2-n)?, and one closely related dinuclear cation of formula [{Ru(apy)(tpy)}2{l-H2N(CH2)6NH2}]4?. The ligand tpy is 2,20:60,200-terpyridine and the ligand L1 is a bidentate ligand, namely, apy (2,20-azobispyridine), 2-phenylazopyridine, or 2-phenylpyridinylmethylene amine. The ligand L2 is a labile monodentate ligand, being Cl-, H2O, or CH3CN. All six species containing a labile L2 were found to be able to coordinate to the DNA model base 9-ethylguanine by 1H NMR and mass spectrometry. The dinuclear cationic species, which has no positions available for coordination to a DNA base, was studied for comparison purposes. The interactions between a selection of four representative complexes and calf-thymus DNA were studied by circular and linear dichroism. To explore a possible relation between DNA-binding ability and toxicity, all compounds were screened for anticancer activity in a variety of cancer cell lines, showing in some cases an activity which is comparable to that of cisplatin. Comparison of the details of the compound structures, their DNA binding, and their toxicity allows the exploration of structure–activity relationships that might be used to guide optimization of the activity of agents of this class of compounds

Could salvage surgery after chemotherapy have clinical impact on cancer survival of patients with metastatic urothelial carcinoma?

The clinical impact of salvage surgery after chemotherapy on cancer survival of patients with metastatic urothelial carcinoma is controversial. We aimed to verify the clinical role of salvage surgery by analyzing the long-term outcome in patients with urothelial carcinoma treated by chemotherapy. Between 2003 and 2010 at a single institution, 31 of 47 patients (66%) with metastatic urothelial carcinoma showed objective responses (CR in 4, PR in 27) after multiple courses of cisplatin/gemcitabine/paclitaxel-based chemotherapy, and a cohort of patients with partial response (PR) were retrospectively enrolled. Twelve (10 male and 2 female, median age 64.0 years) of 27 patients with PR underwent salvage surgeries after the chemotherapy: metastatectomy of residual lesions (10 retroperitoneal lymph nodes, 2 lung), and 6 radical surgeries for primary lesions as well. Progression-free survival and overall patient survival rates were analyzed retrospectively and compared with those of patients without salvage surgery. All 12 patients achieved surgical CR. Pathological findings of metastatic lesions showed viable cancer cells in 3 patients. In univariate analysis, sole salvage surgery affected overall survival in 27 patients with PR to the chemotherapy (P = 0.0037). Progression-free survival and overall survival rates in patients with salvage surgery were better than those in 15 PR patients without the surgery (39.8 vs. 0%, and 71.6 vs. 12.1% at 3 years, P = 0.01032 and 0.01048; log-rank test). Salvage surgery for patients with residual tumor who achieve partial response to chemotherapy could have a possible impact on cancer survival

Late gastrointestinal tissue effects after hypofractionated radiation therapy of the pancreas

Background To consolidate literature reports of serious late gastrointestinal toxicities after hypofractionated radiation treatment of pancreatic cancer and attempt to derive normal tissue complication probability (NTCP) parameters using the Lyman-Kutcher-Burman model. Methods Published reports of late grade 3 or greater gastrointestinal toxicity after hypofractionated treatment of pancreatic cancer were reviewed. The biologically equivalent dose in 1.8 Gy fractions was calculated using the EQD model. NTCP parameters were calculated using the LKB model assuming 1–5 % of the normal tissue volume was exposed to the prescription dose with α/β ratios of 3 or 4. Results A total of 16 human studies were examined encompassing a total of 1160 patients. Toxicities consisted of ulcers, hemorrhages, obstructions, strictures, and perforations. Non-hemorrhagic and non-perforated ulcers occurred at a rate of 9.1 % and were the most commonly reported toxicity. Derived NTCP parameter ranges were as follows: n = 0.38–0.63, m = 0.48–0.49, and TD50 = 35–95 Gy. Regression analysis showed that among various study characteristics, dose was the only significant predictor of toxicity. Conclusions Published gastrointestinal toxicity reports after hypofractionated radiotherapy for pancreatic cancer were compiled. Median dose was predictive of late grade ≥ 3 gastrointestinal toxicity. Preliminary NTCP parameters were derived for multiple volume constraints

Examining Patient Conceptions: A Case of Metastatic Breast Cancer in an African American Male to Female Transgender Patient

An African American male to female transgender patient treated with estrogen detected a breast lump that was confirmed by her primary care provider. The patient refused mammography and 14 months later she was diagnosed with metastatic breast cancer with spinal cord compression. We used ethnographic interviews and observations to elicit the patient’s conceptions of her illness and actions. The patient identified herself as biologically male and socially female; she thought that the former protected her against breast cancer; she had fears that excision would make a breast tumor spread; and she believed injectable estrogens were less likely than oral estrogens to cause cancer. Analysis suggests dissociation between the patient’s social and biological identities, fear and fatalism around cancer screening, and legitimization of injectable hormones. This case emphasizes the importance of eliciting and interpreting a patient’s conceptions of health and illness when discordant understandings develop between patient and physician

Cervical mature teratoma 17 years after initial treatment of testicular teratocarcinoma: report of a late relapse

BACKGROUND: Late relapses of testicular germ cell tumor are uncommon. We report a case of cervical mature teratoma appeared 17 years after treatment of testicular teratocarcinoma. CASE PRESENTATION: A 20- year- old patient underwent left sided orchiectomy followed by systemic therapy and retroperitoneal residual mass resection in 1989. He remained in complete remission for 200 months. In 2005 a huge left supraclavicular neck mass with extension to anterior mediastinum appeared. Radical surgical resection of the mass was performed and pathologic examination revealed mature teratoma. CONCLUSION: This is one of the longest long-term reported intervals of a mature teratoma after treatment of a testicular nonseminoma germ cell tumor. This case emphasizes the necessity for follow up of testicular cancer throughout the patient's life