Neoplasm Recurrence, Local
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Pubmed
Journal: Leukemia & lymphoma
July/14/2015
Abstract

We previously reported that bortezomib indirectly modulates transcription of DNA methyltransferase 1 (DNMT). We designed a phase I study of azacitidine (a direct DNMT inhibitor) plus bortezomib in acute myeloid leukemia (AML) to determine safety and tolerability. Twenty-three adults with relapsed/refractory AML received azacitidine 75 mg/m(2) daily on days 1-7. Bortezomib was dose escalated from 0.7 mg/m(2) on days 2 and 5 to 1.3 mg/m(2) on days 2, 5, 9 and 12. The target dose was reached without dose limiting toxicities. Infection and/or febrile neutropenia were frequent. Patients received a median of 2 cycles of therapy (range, 1-12+). Five of 23 patients achieved remission, including two with morphologic and cytogenetic complete response (CR) and three with CR and incomplete count recovery (CRi). Of CR/CRi responders with cytogenetic abnormalities at baseline, three of four achieved cytogenetic CR. The combination of azacitidine and bortezomib was tolerable and active in this cohort of poor-risk previously treated patients with AML.

Pubmed
Journal: Carcinogenesis
December/16/2013
Abstract

Although estrogen receptor beta (ERβ) has been implicated in prostate cancer (PCa) progression, its potential role in health disparity of PCa remains elusive. The objective of this study was to examine serum estrogens and prostate tumor ERβ expression and examine their correlation with clinical and pathological parameters in African American (AA) versus Caucasian American (CA) men. The circulating 17β-estradiol (E2) was measured by enzyme immunoassay in blood procured from racially stratified normal subjects and PCa patients. Differential expression profile analysis of ERβ was analyzed by quantitative immunohistochemistry using ethnicity-based tissue microarray encompassing 300 PCa tissue cores. In situ ERβ expression was validated by quantitative reverse transcription-PCR in matched microdissected normal prostate epithelium and tumor cells and datasets extracted from independent cohorts. In comparison with normal age-matched subjects, circulating E2 levels were significantly elevated in all PCa patients. Further analysis demonstrates an increase in blood E2 levels in AA men in both normal and PCa in comparison with age- and stage-matched counterparts of CA decent. Histochemical score analysis reveals intense nuclear immunoreactivity for ERβ in tumor cores of AA men than in CA men. Gene expression analysis in microdissected tumors corroborated the biracial differences in ERβ expression. Gene expression analysis from independent cohort datasets revealed correlation between ERβ expression and PCa progression. However, unlike in CA men, adjusted multivariate analysis showed that ERβ expression correlates with age at diagnosis and low prostate-specific antigen recurrence-free survival in AA men. Taken together, our results suggest that E2-ERβ axis may have potential clinical utility in PCa diagnosis and clinical outcome among AA men.

Pubmed
Journal: Thorax
October/31/2001
Abstract

BACKGROUND

Small cell lung cancer (SCLC) represents about 20% of primary lung tumours and the costs associated with the management of SCLC can be significant. The main objective of this study was to obtain information on current patterns of care and associated resource use and costs for patients with SCLC from initial diagnosis and treatment phase, throughout disease progression and terminal care.

METHODS

A 4 year retrospective patient chart analysis (1994-7) was conducted on a consecutive series of 109 patients diagnosed with SCLC in two Newcastle hospitals. For this consecutive series of patients all details about care received including tests and procedures, treatment, and medication from diagnosis till death were recorded. Pathways of care and forms were designed to enable resource use to be captured for different disease phases. Unit costs were determined from a variety of sources including the Newcastle Hospitals NHS Trust Finance Department and the British National Formulary.

RESULTS

The average total cost per patient calculated for the full cohort of 109 patients was pound 11,556. Initial treatment was the most resource use intensive constituting 48.2% of the total cost. The major cost element throughout all disease phases was hospitalisation. Twenty eight percent of the total costs of care occur after recurrence of the disease until death, of which 73% are generated by terminal care.

CONCLUSIONS

The results of this retrospective medical chart analysis show that the costs of care of SCLC are considerable, although the variability between patients in terms of the type and quantity of resource use is very high. Analyses such as this provide a useful insight into resources used in actual clinical practice.

Pubmed
Journal: Journal of vascular and interventional radiology : JVIR
February/7/2016
Abstract

OBJECTIVE

To investigate the prognostic value of R.E.N.A.L. (radius, exophytic/endophytic, nearness to collecting system or sinus, anterior/posterior, and location relative to polar lines) nephrometry score after percutaneous ablation of renal cell carcinoma (RCC).

METHODS

A retrospective 5-year study was performed. Participants were 87 consecutive patients (median age, 67.1 y; 59.7% male, 40.3% female) with 101 biopsy-proven RCCs who underwent percutaneous ablation (54.0% cryoablation, 46.0% radiofrequency ablation). Follow-up computed tomography or magnetic resonance imaging was performed in all cases (mean follow-up, 34.6 mo ± 23.5). R.E.N.A.L. scores were analyzed to determine the association of the score with treatment outcomes and complications.

RESULTS

All tumors corresponded to stage 1A disease. Mean tumor size was 2.05 cm (range, 0.7-3.9 cm), and 50.5% of the lesions measured > 2 cm. Nephrometry score was > 8 in 31.4% of lesions. Overall recurrence rate was 16.8%, first-year recurrence rate was 7.9%, and complication rate was 9.9%. A nephrometry score > 8 was associated with increased complications after percutaneous ablation (P < .0001), increased overall recurrence (P < .0001), and increased risk of first-year recurrence (P < .0001). Immediate complications were associated with tumor size > 2 cm (P < .0001) and risk of local recurrence (P < .001). Age, gender, and percutaneous ablation technique were not correlated with recurrence or immediate complications. Patients undergoing cryoablation had a higher nephrometry score with no significant differences in recurrence rate compared with RF ablation (P = .199).

CONCLUSIONS

A R.E.N.A.L. nephrometry score ≥ 8 predicts recurrence and complications after percutaneous renal ablation.

Pubmed
Journal: Japanese journal of clinical oncology
December/7/1995
Abstract

Sixty cases of primary malignant tumor of the nasal cavity treated in our hospital between 1962 and 1993 were reviewed. Males were affected 2.8 times more frequently than females. The age at the first consultation ranged from 11 to 92 years, with a mean of 55.1 years. The peak distribution was seen in the 6th decade. Twenty-six cases were epithelial malignancies (squamous cell carcinoma 15; adenocarcinoma 3; adenoid cystic carcinoma 3; undifferentiated carcinoma 3; mucoepidermoid carcinoma 1; malignant mixed tumor 1), while 34 cases were non-epithelial malignancies (malignant melanoma 14; malignant lymphoma 14; plasmacytoma 3; olfactory neuroblastoma 2; rhabdomyosarcoma 1). The most common symptom on presentation was nasal obstruction (66.7%), followed by epistaxis (55.0%). The first recurrence was local in 19 patients, whereas cervical lymph node metastasis occurred in three patients, bone metastasis in two, intraperitoneal metastasis in two, and brain metastasis in one. The overall five-year cumulative survival rate was 48.0%. The five-year survival rates for squamous cell carcinoma, malignant melanoma, and malignant lymphoma were 57.0%, 31.0%, and 40.0%, respectively.

Pubmed
Journal: The Journal of laryngology and otology
December/26/2007
Abstract

BACKGROUND

Inverted papillomas are relatively rare, benign epithelial tumours of the nasal cavity which generate considerable interest because they are locally aggressive, have a tendency to recur and are associated with malignancy.

OBJECTIVE

To review our experience of the management of inverted papillomas, and to review the literature in order to evaluate recurrence rates, rates of synchronous and metachronous carcinoma, and outcomes of treatment, both endoscopic and conventional.

METHODS

We retrospectively reviewed all cases of inverted papilloma that presented to our unit, a tertiary referral centre, over a 20-year period from 1985 to 2005. A Medline review of the literature was performed to identify published case series of inverted papillomas. We undertook a critical analysis of the literature.

RESULTS

We treated 65 patients with inverted papilloma over the 20-year period, with a mean follow up of five years (range one to 20 years). Fifty-eight patients initially underwent nasal biopsy, often with polypectomy. Thirty-six had endoscopic surgery, with five (14 per cent) suffering recurrence, whilst 16 had a lateral rhinotomy and medial maxillectomy, of which four (25 per cent) suffered a recurrence. Seven septal inverted papillomas required local resection, with no subsequent recurrences. There were seven (11 per cent) synchronous and two metachronous malignancies.Sixty-three case series with adequate data were identified from the literature. There were 163 (7.1 per cent) cases of synchronous carcinoma, out of 2297 cases. Metachronous carcinomas were reported in 74 out of 2047 cases, representing a transformation rate of 3.6 per cent. However, the true population base for these figures is uncertain, given that many series were reported from tertiary centres, where recurrent and problematic cases are likely to be over-represented. The recurrence rates were 12.8 per cent for endoscopic procedures, 17.0 per cent for lateral rhinotomy with medial maxillectomy, and 34.2 per cent for limited resections such as nasal polypectomy and Caldwell-Luc approaches. No significant association between atypia or dysplasia and recurrence or malignant transformation was found. The mean time taken to develop a metachronous carcinoma was 52 months (range six to 180 months). The estimated malignant potential for recurrent disease was up to 11 per cent.

CONCLUSIONS

Patients with inverted papilloma should undergo thorough surgery to remove all mucosal disease, most probably by the endoscopic, endonasal route when complete resection is possible. Cases demonstrating atypia or dysplasia may be treated by the endoscopic route. Recurrent disease and metachronous carcinoma can develop after a prolonged period of time. Long-term follow up is recommended to detect recurrence, as disease can become quite extensive before it becomes symptomatic.

Pubmed
Journal: Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico
May/25/2014
Abstract

OBJECTIVE

The long-term survival of patients with completely resected stage I non-small cell lung cancer (NSCLC) is not optimal because of undetected lymph node micrometastasis at the time of surgery. The aim of this study is to evaluate the role of survivin and livin mRNA expression in histopathologically negative lymph nodes of stage I NSCLC patients as markers of micrometastasis.

METHODS

Clinical data and tissue samples of primary tumor and lymph nodes were collected from 44 patients with stage I NSCLC. Reverse-transcriptase-PCR (RT-PCR) was used to detect survivin and livin mRNA expression in these tumor and lymph node samples.

RESULTS

Survivin mRNA was detected in all tumors, and livin mRNA was detectable in 39 of the 44 primary tumors. The cut-off values of survivin and livin mRNA levels for diagnosing micrometastasis in lymph nodes were set up according to the expression of survivin and livin mRNA in control lymph nodes. Fifteen (34.1 %) of 44 stage I NSCCL patients had micrometastasis in lymph nodes by survivin and/or livin mRNA positive expression. Survival analysis showed higher rate of cancer recurrences and tumor-related death in patients with lymph node micrometastasis (P < 0.001 and P = 0.001, respectively). Tumor-free survival and overall survival were significantly worse in patients with lymph node micrometastasis compared with those without such micrometastasis (P = 0.007 and P = 0.01, respectively).

CONCLUSIONS

RT-RCR assay for survivin and livin mRNA can be considered as useful diagnostic tool for the detection of lymph node micrometastasis for stage I NSCLC patients.

Pubmed
Journal: HNO
October/14/2003
Abstract

Paragangliomas are tumours of neuroectodermal origin and hormonally active in rare instances. They are very unusual in the paranasal sinuses. We report on the first case--as far as we know--of a recurrent nasal paraganglioma, which started to produce ACTH after a period of ten years and resulted in Cushing's syndrome. Resection of the tumour normalised ACTH and cortisol secretion.

Pubmed
Journal: American journal of rhinology
March/24/2004
Abstract

BACKGROUND

The purpose of this work is to evaluate our results in the treatment of the nasal inverted papillomas with an endoscopic approach using a retrospective case series.

METHODS

Between 1993 and 2000 we treated 27 patients with nasal inverted papillomas. All patients underwent endoscopic nasal surgery under general anesthesia. None of the inverted papillomas extended outside of the paranasal sinuses. All tissue samples underwent polymerase chain reaction and hybridization in situ to detect genetic sequences of the human papilloma virus and Epstein Barr virus.

RESULTS

The study population consisted of 16 men and 11 women with a median age of 52 years (range, 22-77 years). Ten patients (37%) had undergone a previous nasal surgery. The median follow-up was 5 years (range, 2-8 years). None of the patients presented with bilateral nasal involvement or a synchronous carcinoma. Seven patients underwent an additional surgical approach (two endoscopic approaches via a Caldwel-Luc approach, four sublabial approaches via a Caldwel-Luc approach, and one external ethmoidectomy). There were no surgical complications. Two patients (7%) had recurrent papilloma 4 and 6 years after surgery and again underwent endoscopic resection. The amplification both by polymerase chain reaction and hybridization in situ for human papilloma virus and Epstein Barr virus were negative in the specimens from all patients.

CONCLUSIONS

According to the literature and our own experience, we believe that the initial surgical management of primary and recurrent inverted papillomas limited to the nasal cavity and paranasal sinuses should be endoscopic sinus surgery.

Pubmed
Journal: Lung cancer (Amsterdam, Netherlands)
April/21/2004
Abstract

OBJECTIVE

Bronchioloalveolar carcinoma (BAC) is a subtype of lung adenocarcinoma whose incidence is raising. Bronchioloalveolar carcinoma has a tendency to involve diffusely the lung. No agreement exists about whether diffuse bronchioloalveolar carcinoma has a multicentric or unicentric origin. The purpose of this work is to evaluate the correlation between intrapulmonary spread of bronchioloalveolar carcinoma and its histologic and immunohistochemical characteristics.

METHODS

Surgical specimens of 20 bronchioloalveolar carcinomas with radiologically proved evolution from focal to diffuse disease were retrieved and reviewed. Patterns of pulmonary spread were defined on the basis of CT and MR imaging examinations. Immunohistochemical studies were performed to investigate the expression of gelatinase A and alpha2-integrin. Correlation between immunohistochemical results and patterns of pulmonary spread was evaluated. Statistical evaluation was performed by using Fisher Exact Test.

RESULTS

Three histological subtypes of bronchioloalveolar carcinoma were found: mucinous (11 cases), non-mucinous (3 cases), and mixed adenocarcinoma with prominent bronchioloalveolar pattern (6 cases). Three patterns of pulmonary spread were depicted radiologically: parenchymal opacification (11 cases), multiple nodules (7 cases) and mixed pattern (2 cases). Eleven out of 12 mucin-producing versus none out of 8 non-mucin producing cancers developed parenchymal opacification. The difference was statistically significant (P<0.028). A statistically significant difference was also found between the development of parenchymal opacification and the level of alpha2-integrin: 11 out of 13 tumors with negative alpha2-integrin versus none out of 7 with positive alpha2-integrin immunoreactivity (P>0.033).

CONCLUSIONS

Diffuse bronchioloalveolar carcinoma may develop from a prior focal cancer. Mucinous subtype is the most prone to develop diffuse disease with parenchymal opacification, probably representing aerogenous spread. Low levels of alpha2-integrin receptors were found in bronchioloalveolar carcinoma which developed parenchymal opacification.

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