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Biomedical subjects

D Hardisson

Publications and source records attributed to D Hardisson.

At least 19 recordsLinked to original sources

Breast cancer prognosis determined by gene expression profiling: a quantitative reverse transcriptase polymerase chain reaction study.

PURPOSE: We sought to reproduce with quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR) the results obtained with a 70-gene expression profile that has been described previously in breast cancer. PATIENTS AND METHODS: Frozen breast cancer samples from patients who were operated on were used to isolate tumor RNA. Ninety-six patients with stage I to II disease were included. Median age was 57 years (range, 27 to 80 years). Forty-eight patients had lymph node-negative and 48 lymph node-positive disease. qRT-PCR amplifications were performed and the results were correlated with clinical data. RESULTS: After a minimum follow-up of 5 years, 25 patients had a relapse. The gene profile divided patients into two groups with poor and good prognosis. Significant differences with regard to grade of differentiation, size and hormone receptors were seen between the two groups. The gene profile was significantly associated with relapse-free survival and overall survival in the whole group of 96 patients. Multivariate analysis showed that only lymph node status and gene profile were significantly correlated to overall survival. CONCLUSION: qRT-PCR reproduced the results obtained with microarrays for a prognostic gene profile in women with early-stage breast cancer.

Adult↗

Fine needle aspiration cytology of mammary carcinoma with osteoclast-like giant cells.

Carcinoma with osteoclast-like giant cells (OCGC) is an uncommon neoplasm characterized by giant cells, prominent vascularization, haemorrhage and areas of cribriform epithelial growth with moderate atypia. Multinucleated giant cells (MGC) have been described in several other breast lesions raising an interesting differential diagnosis, mainly with benign disorders. Due to its rarity few cases have been described cytologically. We retrospectively reviewed 13 fine needle aspiration samples from nine patients with this variant of carcinoma. Nine corresponded to breast tumours and four to axillary, liver, subcutaneous and mediastinal metastatic lesions. The expression of CD68 by giant cells was evaluated immunocytochemically in six cases. All patients had a complete pathological study of the breast neoplasm. Smears showed a double component of epithelial and giant cells. Epithelial clusters were predominantly of intermediate size with irregular contours. Most were cohesive but others showed cellular dissociation with scarce to moderate cellular pleomorphism. Giant cells had well defined, deeply stained cytoplasm and round to elongated morphology. Two metastatic cases were devoid of them. Haemosiderin-laden macrophages were common in smears from breast tumours. In the six cases tested CD68 was expressed in MGC. Cytological features of mammary carcinoma with OCGC correlate closely with the histological ones. Most cases are clearly recognizable as malignant but in others cytological atypia may be minimal, mimicking a benign lesion. In difficult cases the presence of haemosiderin-laden macrophages and the histiocytic nature of the MGC are helpful diagnostic features.

Adult↗

New insights in beta-tubulin sequence analysis in non-small cell lung cancer.

Scarce data are available regarding the molecular mechanisms implicated in paclitaxel resistance. There is controversial data about beta-tubulin mutations role in paclitaxel resistance. We have conducted this trial to address the influence of beta-tubulin mutations in paclitaxel resistance in advanced non-small cell lung cancer (NSCLC). A group of 15 patients were biopsied and diagnosed of stages IIIB and IV NSCLC. Tumor specimens were used for DNA isolation and exon 4 of HM40 beta-tubulin isotype was amplified and automatically sequenced, using both intronic and exonic primers. Next, the chemotherapy schedule consisted of weekly paclitaxel (100 or 150 mg/m(2) x 6) followed 2 weeks later by cisplatin 100 mg/m(2) on day 1, gemcitabine 1000 mg/m(2) on days 1 and 14, and vinorelbine 25 mg/m(2) on days 1 and 14, every 28 days. Using exonic primers, gene sequence alterations were found in 13/15 (87%) patients, including transitions (codons 180 and 182) and one silent transversion (codon 195). Also, three transversions (codons 231, 234, and 235) were found in all patients and controls. All alterations disappeared when sequenced with intronic primers. Our results suggest that point mutations demonstrated with exonic primers but not with intronic ones are probably due to beta-tubulin pseudogenes present in advanced NSCLC specimens. Even so, when these beta-tubulin pseudogenes are found there is a clear relation with clinical response. Although these changes could be relevant in paclitaxel resistance, this observation must be proven in future clinical trials to resolve "the tubulin dilemma".

Adenocarcinoma↗

[Bronchocentric granulomatosis and pulmonary hydatidosis].

Bronchocentric granulomatosis is a non-specific necrotizing granulomatous reaction in the bronchi and bronchioles. In asthmatic patients, bronchocentric granulomatosis is considered a hypersensitivity reaction to intrabronchial fungi. However, in non-asthmatic patients the possible etiology has not been identified. We report the case of a 46-year-old woman with bronchocentric granulomatosis associated with pulmonary hydatidosis. The likely immuno-pathogenic mechanisms leading to bronchial lesions are briefly discussed.

Bronchi↗

Post-transplant lymphoproliferative disease in tonsils of children with liver transplantation.

OBJECTIVE: To assess the incidence and characteristics of post-transplant lymphoproliferative disease (PTLD) in tonsils of the liver transplanted children. METHODS: All patients under 14 years of age recipients of a liver transplant at the institution and operated on for tonsillectomy under suspicion of malignancy were included in this study. RESULTS: Seven patients underwent surgery on their tonsils under suspicion of PTLD. One case of B-cell lymphoma, and three cases of polymorphic diffuse B-cell hyperplasia were found. This represents an incidence of 1.4% of PTLD in the tonsils of the 283 pediatric liver transplants performed at the hospital. CONCLUSION: The incidence of PTLD in tonsils after liver transplantation is very low at the institution. However, it is very important to follow-up allograft recipients for early diagnosis of this entity.

Child↗

Graft-vs-host disease as a cause of enlargement of the epiglottis in an immunocompromised child.

We report a rare case of dyspnea due to enlargement of the epiglottis in a severely immunocompromised patient. The child underwent a previous tracheostomy at another hospital because of respiratory distress under the diagnosis of acute epiglottitis. The patient was subsequently decannulated without incident. One year later, the child developed a new episode of dyspnea with inspiratory stridor. A new tracheostomy was neccessary, and a biopsy specimen of the enlarged epiglottis was taken to confirm the diagnosis of graft-vs-host disease. The therapeutic measures in these situations are discussed below, and a review of the current literature concerning the etiology and management of epiglottic enlargement is performed.

Child, Preschool↗

Primary osteosarcoma of the uterine corpus: report of a case with immunohistochemical and ultrastructural study.

BACKGROUND: Primary uterine osteosarcoma is extremely rare, with only 15 cases reported in the literature. CASE: A 41-year-old woman presented with abnormal vaginal bleeding due to a large tumor arising from the uterine corpus. Histologically, the tumor showed the features of a malignant mesenchymal neoplasm with osteoid formation and lacked an epithelial component. Immunohistochemical and ultrastructural studies showed no evidence of epithelial differentiation. The tumor was excised and the patient received chemotherapy and radiation therapy postoperatively, but the tumor recurred locally at the 8-month follow-up. CONCLUSION: Osteosarcoma as a primary uterine tumor is exceedingly rare and should be distinguished from carcinosarcoma, which shows different macroscopic and histologic features. Prognosis of this neoplasm is very poor with an average life expectancy of 5 months.

Adult↗

Crohn's disease limited to the appendix.

BACKGROUND: Crohn's disease confined to the vermiform appendix is rare. In our study, the incidence was 0.2% of all patients diagnosed with Crohn's disease at La Paz University Hospital, Madrid, Spain, in 20 years. METHODS: Here we review the clinical records of 10 patients with isolated appendiceal Crohn's disease. RESULTS: Preoperative diagnosis was acute appendicitis in all 10 cases, and all patients underwent appendectomy. Postoperative complications were limited to an enterocutaneous fistula in 1 patient. There was no evidence of recurrence during a mean follow-up period of 14.5 years (range 2 to 25 year). CONCLUSIONS: We conclude that Crohn's disease when confined to the appendix is less aggressive than in other sections of the intestine, with a low recurrence rate and incidence of postoperative fistula.

Adolescent↗

The prognostic significance of P-cadherin in infiltrating ductal breast carcinoma.

We have immunohistochemically investigated P-cadherin (P-CD) expression in a series of 210 infiltrating ductal carcinomas (IDC) in an attempt to assess the biological and prognostic relevance of P-CD in patients harboring IDCs. Although only 74/210 (35%) of IDCs expressed P-CD in >5% of tumor cells (P-CD-positive carcinomas), categorical analyses revealed that P-CD-positive IDCs were larger (26 +/- 21 cm versus 22 +/- 11 cm, P =.0568), of higher histological grade (P =.0001), and had more lymph node metastases (P =.0327) than P-CD-negative breast carcinomas. In addition, P-CD-positive tumors were negative for estrogen (P =.0001) and progesterone receptors (P =.0001) and showed reduced E-cadherin expression (P =.0276) more frequently than P-CD-negative tumors. Univariate analysis carried out in 171 patients demonstrated that P-CD expression was also an indicator of poor prognosis (chi(2) = 8.292, P =.004), extent of lymph node metastasis (chi(2) = 20.854, P =.0000), histological grade (chi(2) = 12.908, P =.0016), and negative progesterone receptors (chi(2) = 4.116, P =.042). However, only histological grade and nodal metastases emerged as independent prognostic markers in the multivariate analysis. These results suggest that although P-CD expression may be involved in the progression of IDCs, its value as an independent prognostic factor remains to be established.

Adult↗

Factors related to nerve injury and hypocalcemia in thyroid gland surgery.

To identify potential risk factors related to complications after thyroidectomy, a study was designed that included 675 patients. Recurrent laryngeal nerve (RLN) paralysis, hypocalcemia, serohematoma, wound infection, and postoperative hemorrhage were evaluated. The rate of paralysis of the RLN was calculated on nerves at risk for hypocalcemia (n = 890) in patients undergoing bilateral procedures or unilateral procedures if they had previously undergone a contralateral operation (n = 321). Multivariate analysis was used to identify the relationships between the variables included in the study. All statistical tests received the same level of significance of 0.05. Permanent hypocalcemia occurred in 2.2% of the patients, whereas unilateral paralysis of the RLN developed in 0.9%. Mortality was 0.1% in this series. The RLN paralysis had a significant relationship with preoperative diagnosis of malignancy (P < 0.03). Likewise, hypocalcemia was related to sex and surgical procedure (P < 0.03). Serohematoma was linked with age (P < 0.001), and hemorrhage was associated with previous radiation of the neck (P < 0.03).

Adolescent↗

Pilomatrix carcinoma: a clinicopathologic study of six cases and review of the literature.

Pilomatrix carcinoma, the malignant variant of pilomatrixoma, is a rare entity. The authors report on six patients with pilomatrix carcinoma and review the pertinent literature. The lesions showed a predilection for elderly individuals (mean age, 61 years) with a male:female ratio of 5:1, and they presented as dermal or subcutaneous tumors located on the head and neck (5 neoplasms) and chest (1 neoplasm). Tumors varied in size from 0.6 cm to 2.5 cm (mean, 1.78 cm). None of the lesions recurred after wide local excision. On scanning magnification, all tumors showed the architectural features of a malignant neoplasm (asymmetry and poor circumscription, presence of several markedly sized and variably shaped basaloid aggregations, and ulceration). The tumors were composed of pleomorphic basaloid cells with prominent nucleoli and frequent atypical mitoses accompanied by central areas with keratotic material, shadow cells, and foci of necrosis. The tumor nests were surrounded by a desmoplastic stroma and infiltrated the adjacent tissues. Vascular or perineural infiltration was not observed. In one case, the basaloid cells contained abundant melanin pigment in their cytoplasms. Pilomatrix carcinoma is a neoplasm of low-grade malignancy that should be distinguished from the conventional pilomatrixoma and its variants (aggressive pilomatrixoma and proliferating pilomatrixoma), matricoma, and basal cell carcinoma with matrical differentiation. Clinicians and pathologists should be aware of the occurrence of pilomatrix carcinoma because of its potential for distant metastases.

Adult↗

Sarcomatoid carcinoma of the pyriform sinus with brain and subcutaneous metastases: an unusual metastatic spread pattern.

A 63-year-old man presented a polypoid tumor in the laryngeal space involving the right pyriform fossa. The patient underwent a total laryngectomy with bilateral functional neck dissection, and the diagnosis of sarcomatoid carcinoma with malignant fibrous histiocytoma-like stroma was established. The tumor showed an uncommon behavior, with distant metastases to the brain and to the subcutaneous tissue of the abdominal wall. The patient died 1 year after the development of the metastases. Despite its polypoid pattern of growth, sarcomatoid carcinoma of the larynx may behave very aggressively. It is important for clinicians to be aware of the possibility of distant subcutaneous and brain metastases in sarcomatoid tumors of the laryngeal space. If such metastases develop, the prognosis is ominous, with an average life expectancy of 3 months.

Abdominal Neoplasms↗

Postoperative radiotherapy in patients with positive nodes after functional neck dissection.

A study was designed to assess the usefulness of postoperative radiotherapy (RT) in patients with surgically treated laryngeal and hypopharyngeal cancer with histologically proven positive neck nodes. Patients underwent operation between 1984 and 1995, with functional neck dissection (FND) being part of the treatment in all cases. The selection criteria included squamous cell carcinoma, negative margins for the primary tumor, and no previous treatment. For evaluation purposes, patients were divided into 2 groups: surgery alone versus surgery with postoperative RT. Eighty-three patients fulfilled the inclusion criteria and entered the study. All but 1 of the patients were men. The mean age was 58 years (range, 35 to 77 years). A multivariate analysis was used to analyze the prognostic parameters selected by univariate analysis, eg, age, alcohol, tumor location, T and N stages, and presence or absence of extracapsular spread and a desmoplastic pattern. Postoperative RT was not selected by univariate analysis as a prognostic factor, but was included in the multivariate analysis in order to assess its impact on survival and recurrence rates. Using the statistical method of multivariate analysis, we could not find evidence of a benefit to survival or local recurrence rates with postoperative RT in this series. Patients younger than 55 years and those with extracapsular spread had a decreased survival rate and a higher neck recurrence rate, irrespective of the treatment method.

Adult↗

Extracapsular spread and desmoplastic pattern in neck lymph nodes: two prognostic factors of laryngeal cancer.

The influence of extracapsular spread (ECS) and a desmoplastic pattern (DP) of metastatic cervical lymph nodes in patients with laryngeal cancer is presented. The study includes 128 patients surgically treated between 1984 and 1992 for squamous cell carcinoma of the larynx with pathologically proven lymph node metastasis. The results were studied from 2 major standpoints: survival and recurrence. The 3-year survival rates were as follows: patients without ECS 73.4%, and with ECS 28.9% (p < .001); patients without a DP 76.9%, and with a DP 43.3% (p < .03). Also, the 3-year recurrence rates in the neck showed significant differences: patients without ECS 10.7%, and with ECS 49.6% (p < .001); patients without a DP 10%, and with a DP 31.6% (p = .1142). Postoperative radiotherapy did not appear to improve the outcome.

Actuarial Analysis↗