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Biomedical subjects

A G Ayala

Publications and source records attributed to A G Ayala.

At least 19 recordsLinked to original sources
PubMed1996

Conventional and dedifferentiated parosteal osteosarcoma. Diagnosis, treatment, and outcome.

BACKGROUND: Dedifferentiated parosteal osteosarcoma (dd-POS) designates high grade transformation, of conventional low grade parosteal osteosarcoma (c-POS). The paradigm of preoperative diagnosis, neoadjuvant chemotherapy, and wide local excision has not been adequately evaluated for dd-POS, as it has been for conventional high grade intramedullary osteosarcoma. METHODS: A retrospective review was conducted of 28 patients treated at the authors' institution between January 1980 and December 1992 for an osteosarcoma arising on the surface of the bone diagnosed as either c-POS or dd-POS. The clinicopathologic features, diagnosis, treatment, and patient outcome were analyzed. RESULTS: A dedifferentiated component was identified in 12 of 28 tumors (43%). Neither the presence of radiolucencies (77% in c-POS and 100% in dd-POS, P = 0.06) nor medullary invasion (42% in c-POS and 50% in dd-POS, P = 0.28) distinguished dd-POS from c-POS. However, all patients who presented with focal hypervascularity on an arteriogram defined the high grade component of dd-POS that was confirmed by selective needle biopsy. This differed significantly (P = 0.00003) from c-POS. None of the patients with c-POS died of the disease (median survival duration, 77 months; range, 16-152 months). Six patients (35%) developed a local recurrence, but five were treated successfully with further surgery. In the dd-POS group, 7 of the 12 patients died of the disease. Ten patients with dd-POS received preoperative chemotherapy (IA cis-diamminedichloroplatinum, IV doxorubicin), and a good response (> 90% necrosis of high grade component) was observed in four. Among patients whose disease was localized, continuous disease free survival was prolonged significantly (P = 0.03) in patients with a good response (median, 75 months) compared with those who responded poorly (median, 13 months). Five patients remained continuously disease free (median, 66 months, range, 29-95 months). CONCLUSIONS: Wide surgical excision alone is adequate treatment for patients with c-POS. Recognition of dedifferentiated areas with angiography and percutaneous biopsy of hypervascular areas should prompt the administration of chemotherapy and wide local excision to optimize patient outcome.

Adolescent↗
PubMed1996

Chondrosarcoma of the pelvis. Prognostic factors for 67 patients treated with definitive surgery.

BACKGROUND: Chondrosarcoma (CS) most commonly involves the pelvis. Local and systemic failures often result in poor outcome. Prognostic factors that determine patient outcome remain ill-defined. METHODS: We retrospectively analyzed 67 patients with CS of the pelvis treated by definitive surgery from January 1970 to December 1992. All patients had localized disease including Grade 1 (19 patients), Grade 2 (18 patients), Grade 3 (17 patients), and dedifferentiated (13 patients) tumors. Thirty-two patients underwent a limb-sparing surgical resection and 35 patients underwent hemipelvectomy. Follow-up was available for all patients. The median duration of follow-up for the survivors was 115 months (range, 24-288 months). RESULTS: At last follow-up, 52% of the patients were disease free, 8% were alive with disease, 36% died of disease, and 4% died of other causes. Nineteen patients (28%) had developed a local recurrence (LR). The median time to LR was 23 months (range, 1-111 months). Independent variables in a multivariate analysis associated with increased risk of LR included inadequate surgical margin, tumor epicenter in the pubis, and high grade histology. LR did not influence overall patient survival. Twenty-three patients (36%) developed distant metastases at a median time of 9 months (range, 1-111 months) postoperatively. Metastases developed in 0% of the patients with Grade 1, 20% of the patients with Grade 2 60% of the patients with Grade 3 and 75% of patients with dedifferentiated CS. On multivariate analysis, histologic high grade was the only significant predictive variable for distant relapse (P = 0.005). CONCLUSIONS: The critical issue for a favorable outcome in low grade CS of the pelvis is adequate surgical excision (i.e., negative surgical margin). The high rate of systemic failure in high grade and dedifferentiated CS, despite adequate surgery, emphasizes the need for more effective systemic therapy.

Adult↗
PubMed1996

Intraabdominal desmoplastic small cell tumor. Report and discussion of five cases.

BACKGROUND: Intraabdominal desmoplastic small cell tumor is a rare malignancy that has only recently been described. In the adult population, it is usually seen in young males. The tumor appears to arise as a dominant mass or masses in the abdominal cavity, particularly in the pelvic region, without a clear visceral origin. Multiple small tumor nodules may be found attached to the peritoneal surface. Visceral metastases occur late in the clinical course, ultimately leading to the patient's death. Five young adults with intraabdominal desmoplastic small cell tumors were treated with aggressive chemotherapy. METHODS: Charts of five patients treated between 1990 and 1995 were reviewed. The diagnosis of desmoplastic small cell tumor was made on the basis of typical clinical and radiographic findings, light microscopy showing hyperchromatic cells surrounded by a desmoplastic stroma, and immunohistochemistry demonstrating markers of epithelial and mesenchymal differentiation. Patients were treated with aggressive combination chemotherapy consisting of alternating regimens similar to those used as testis cancer salvage therapy. RESULTS: Four of the five patients demonstrated a partial response to chemotherapy. Two of the responding patients had surgery with the intent of removing all residual disease, but this was successful in only one case. All patients have died from their cancer. CONCLUSIONS: Intraabdominal desmoplastic small cell tumors are sensitive to combination chemotherapy. It appears that treatment offers good palliation and may prolong survival in isolated cases. However, even the patients managed with the most aggressive medical and surgical approaches are not cured and ultimately die of their disease.

Abdominal Neoplasms↗
PubMed1996

Avulsion fracture of the anterior inferior iliac spine with abundant reactive ossification in the soft tissue.

Patients who have sustained an avulsion fracture and present clinically during the healing phase of the injury may manifest a mass that clinically and radiographically mimics a malignant neoplasm. A 15-year-old male soccer goalkeeper presented with a large ossified mass in the soft tissues overlying the right hip 6 months after experiencing a popping sensation in his hip joint during a game. Although an osteosarcoma was suspected clinically and radiographically, a Tru-Cut needle biopsy of the lesion revealed reactive bone formation. Correlation of the clinical, radiographic, and pathologic findings indicated an avulsion fracture of the anterior inferior iliac spine with abundant reactive ossification in the soft tissues. The healing phase of an avulsion fracture may clinically and radiographically be mistaken for neoplasia. In such cases, a Tru-Cut needle biopsy may reveal the reactive nature of the process.

Adolescent↗
PubMed1996

Anaplastic variant of spermatocytic seminoma.

Four examples of spermatocytic seminoma with a predominant anaplastic component occurred in men 33 to 43 years of age, without histories of cyptorchidism. The seminomas presented with painless testicular masses recognized 3 to 18 months before orchiectomy. Preoperative serum measurements of human chorionic gonadotropin and alpha-fetoprotein were negative. All tumors contained areas (10% to 30% of the tumor) in which the three cell types characteristic of conventional spermatocytic seminoma could be identified under light microscopy. The predominant anaplastic component also contained the three cell types, but the nuclei had prominent nucleoli with granular and filamentous chromatin. In addition, sheets of cells with vesicular nuclei and prominent nucleoli superficially resembling embryonal carcinoma were found. There were numerous large mononuclear and multinucleated giant cells with bizarre nuclei and prominent nucleoli, but no sarcomatous elements. Many normal and abnormal mitotic figures were present. Tunical and vascular invasion and extensive necrosis were constant features. Immunohistochemistry documented p53 protein overexpression in two tumors, but neoplastic cells were negative with immunostains for placenta-like alkaline phosphatase, leukocyte common antigen, neuron-specific enolase, alpha-fetoprotein, human chorionic gonadotropin, vimentin, and cytokeratins. Ultrastructural examination of the anaplastic component showed large rope-like nucleoli, but the cytoplasmic features were similar to those of conventional spermatocytic seminoma. Despite the presence of a major anaplastic component, no patient has developed metastasis. Larger series and longer follow-up are needed to understand the natural history of these neoplasms.

Adult↗
PubMed1996

Allergic fungal sinusitis: a clinicopathologic study of 16 cases.

Allergic fungal sinusitis (AFS) has been clinicopathologically defined as a noninvasive form of fungal infection. Etiologically, most reported cases have been attributed to pigmented dematiaceous fungi. The authors report 16 cases of AFS from our institution, along with a review of cases from the literature. The patients' age ranged from 8 to 71 years, with a mean age of 25 years. All patients were immunocompetent, although six had a strong history of atopy. Multiple sinuses were affected in all cases; nine patients had bilateral involvement, and seven patients manifested unilateral involvement. Histopathologically, all cases were characterized by the presence of "allergic mucin," with scattered fungal organisms without invasion of mucosa or bone. Fontana-Masson stain identified fungi in all but one case and assisted in distinguishing the pigmented dematiaceous organisms from other septated fungal forms. Accordingly, Fontana-Masson stain can be useful in confirming the diagnosis of AFS in the lack of tissue culture results. Fungal cultures performed on six cases grew Exserohilum (three cases), Bipolaris (one case), Drechslera (Bipolaris) (one case), and Curvularia (one case). All patients were treated with surgical debridement and sinus aeration. Follow-up of at least 6 months was obtained in six cases, of which four showed recurrent disease between 8 months and 4 years after the initial surgical procedure. A literature review showed that the most common etiologic agents were members of the dematiaceous family (81%), with the most common genus being Bipolaris (42%), followed by Curvularia (21.3%). It is believed that type I and III hypersensitivity reactions underlie the pathogenesis of this disease.

Adolescent↗
PubMed1996

Endocervical type glands in urinary bladder: a clinicopathologic study of six cases.

The authors report six cases of glandular lesions made up of endocervical type glands in the urinary bladders of women aged 34 to 65 years (mean, 39 years). Two patients presented with dysuria, one with painless hematuria, one with complaints of pelvic discomfort and hematuria, and one with vaginal discharge. The sixth patient was asymptomatic, but on a routine gynecologic examination, a pelvic mass was found. On physical examination, three women had masses between the bladder and uterus. Four lesions were located in the posterior wall of the urinary bladder, one in the dome, and one in the trigone. Four patients underwent biopsy of the bladder lesion. One of these patients had undergone a hysterectomy 10 years earlier. One woman with a pelvic mass between the bladder and uterus underwent a hysterectomy, bilateral salpingo-oophorectomy, and partial cystectomy. The sixth patient had a transurethral resection of the bladder tumor and left oophorectomy. Histologically, all cases showed intermediate to large-sized irregularly shaped endocervical type glands in the muscularis propria of the urinary bladder. Some glands exhibited cystic dilatation and contained mucinous secretions. The glands elicited no desmoplastic tissue reaction. The intraluminal mucin frequently contained polymorphonuclear leukocytes. In all cases, the glands were lined by mucinous, tall, columnar cells and less commonly by flattened to cuboidal cells. Rare admixed ciliated cells were also observed. The lining epithelium was bland in five cases, but moderate nuclear atypia was seen in one case. Mitoses were not observed in any case. Associated lesions included endometrial type glands surrounded by elastotic stroma in one case, exuberant cystitis glandularis in one case, and a pseudodiverticulum of the bladder in one case. Review of the slides from the patient who had had a hysterectomy 10 years previously revealed endocervical adenocarcinoma in situ. Follow-up (mean = 30 months; range = 6 to 60 months) shows that all patients are alive and well, suggesting that the lesion is benign.

Adult↗
PubMed1996

Spermatic cord contamination in testicular cancer.

It is not uncommon to find testicular germ-cell tumors in the spermatic cord. This may represent contamination or true involvement (vascular invasion or direct tumoral extension into the cord). A correct identification of the process has important clinical implications. In a review of 326 testicular germ-cell tumors, 79 (24.2%) revealed tumor in the spermatic cord. Of these 79, contamination was found in 57 (72.1%), true involvement in 15 (19%), and true involvement and contamination in 7 (8.9%). Spermatic cord contamination was seen most frequently with seminomas: 34 (24.1%) of 141 seminomas and 20 (15.4%) of 130 mixed germ-cell tumors. Eighteen of the 20 mixed germ-cell tumors contained an embryonal carcinoma component. True involvement was seen most frequently in embryonal carcinoma. Six (15.4%) of 39 pure embryonal carcinomas demonstrated true cord involvement. Six mixed germ-cell tumors with true cord involvement contained an embryonal carcinoma component. Distinguishing between true involvement of the spermatic cord and contamination can occasionally be problematic. Because true involvement, especially at the spermatic cord resection margin, identifies patients at a high risk for relapse, the problem of contamination caused by inadequate precautionary measures can be avoided by meticulous handling and processing of the specimens.

False Positive Reactions↗
PubMed1995

p53 expression in dedifferentiated chondrosarcoma.

BACKGROUND: p53 acts as a tumor suppressor gene because of to its negative control of the cell cycle and its central role in programmed cell death. It frequently is mutated, as observed in a variety of human neoplasms. The mutations inhibit tumor-suppressor activities of p53, which may gain a new function of tumor promotion. In this study, p53 was investigated in various components of dedifferentiated chondrosarcoma and correlated with their proliferative activities. METHODS: Immunohistochemical assays for p53, Ki-67, and proliferating cell nuclear antigen (PCNA) were used in a series of eight dedifferentiated chondrosarcomas of bone. The cartilaginous component was low grade (Grade I-II) in five cases. It was predominantly low grade with foci of a high grade (Grade III) chondrosarcoma in the remaining three cases. The noncartilaginous (dedifferentiated) high grade component consisted of malignant fibrous histiocytoma in five cases and osteosarcoma in three. RESULTS: Regardless of the histological type, diffuse strong nuclear staining for p53 occurred in the high grade noncartilaginous component of all eight of the tumors. The low grade cartilaginous component of six cases was negative for p53, with focal weak staining in the two remaining cases. The high grade cartilaginous component showed strong positive staining for this protein in all three cases. Ki-67 and PCNA expression were similar to that of p53. CONCLUSIONS: The percentage of p53 positive staining roughly was parallel to the proliferating fraction of cells in various components of dedifferentiated chondrosarcoma. Moreover, p53 overexpression was consistently present in the high grade noncartilaginous (dedifferentiated) component of the tumor and was accompanied by increased proliferative activity.

Cell Differentiation↗
PubMed1995

Detection of residual prostate cancer after external radiotherapy. Role of prostate specific antigen and transrectal ultrasonography.

BACKGROUND: Although the incidence of positive post-radiotherapy biopsies has been reported, the range is considerable (19-93%) and depends partly on patient-selection criteria. In addition, the prognostic significance of transrectal ultrasonography (TRUS) and prostate specific antigen (PSA) used alone and in combination in predicting residual cancer after radiotherapy has yet to be determined. METHODS: Transrectal ultrasonography-guided prostate biopsies were performed on 31 unselected patients with prostate cancer 34-77 months (mean, 51 months) after definitive external beam radiotherapy was completed. Biopsy results were compared for pre- and posttreatment parameters (clinical stage, grade, PSA, and TRUS). RESULTS: In 22 patients (71%), residual cancer was detected histologically by biopsy. All but one patient (12/13, 92%) with a pretherapy PSA value greater than 10 ng/mL had a positive biopsy compared with 50% of those (7/14) with a pretherapy PSA value less than or equal to 10 (P < 0.05). After radiotherapy, a positive biopsy was noted for 15 of 16 patients (94%) with a PSA value greater than 2 and in 20 of 23 (87%) of those with abnormal TRUS findings (P < 0.01 and P < 0.005, respectively). CONCLUSIONS: The most clinically useful model for predicting histologically identifiable residual cancer was either a serum PSA value greater than 2 or a PSA value less than or equal to 2 and abnormal TRUS findings. The positive and negative predictive values of the model were 84% and 83%, respectively. The model predicted biopsy results correctly in 26 of 31 patients (84%). Transrectal ultrasonography is recommended as a diagnostic tool for patients whose PSA level ranges from a detectable level to less than or equal to 2 ng/mL.

Aged↗
PubMed1995

DNA and RNA content analysis by flow cytometry in the pathobiologic assessment of bone tumors.

Studies of simultaneous DNA and RNA contents by flow cytometry in hematologic and some solid neoplasms have been shown to provide information that may be useful in the pathobiological evaluation of these neoplasms. We contend that similar analysis may be equally valuable in assessing bone tumors. Our data revealed significant statistical differences in DNA ploidy and proliferative fraction between benign and malignant bone neoplasms. Benign tumors manifested predominantly DNA diploidy and low proliferative activity, whereas the majority of malignant tumors were DNA aneuploid and showed high proliferation rate. No significant difference in the RNA content between different histopathologic categories was found. We observed, however, a distinct and consistently high RNA content pattern in giant cell tumors, aneurysmal bone cysts, and chondroblastomas that may be useful in their differential diagnosis. Analysis of different prognostic factors in malignant tumors indicated that histologic grade and DNA content are a significant prognostic factors. Further analysis of malignant tumors showed that a correlation between the proliferative activity and the clinical outcome in the low grade category and between RNA content and patients' survival in osteosarcomas. Our study also showed that preoperative treatment significantly impacted on the extent of the proliferative fraction in malignant tumors. We conclude that DNA/RNA analysis of bone tumor may assist in: (1) the differential diagnosis of certain bone tumors, (2) evaluation of treatment response, and (3) the biological assessment of osteosarcomas.

Acridine Orange↗
PubMed1995

The prognostic importance of Gleason grade in prostatic adenocarcinoma: a long-term follow-up study of 648 patients treated with radiation therapy.

PURPOSE: It is common practice to histologically grade adenocarcinoma of the prostate using the Gleason system. Whereas the prognostic utility of this grading is well known, few studies have comprehensively evaluated it for patients undergoing definitive radiation therapy and generally accepted guidelines as to which Gleason grades should be "lumped" have not been established. This study reports the results of univariate and multivariate evaluation of the prognostic significance of Gleason grade in 648 patients followed for a median of 6.5 years after radiation therapy for T1 to T4, N0, or NX, MO prostate cancer. METHODS AND MATERIALS: The correlation between Gleason grade and local recurrence, metastatic relapse, any disease relapse, and patient survival was evaluated using univariate and multivariate methods. Analysis was also stratified according to whether the grading was assigned on a needle biopsy or on a transurethral resection specimen. RESULTS: The large number of Gleason grades required grouping of grades for meaningful analysis and we found that a four-tier system (grades 2 and 3, 155 patients; grades 4-6, 290 patients; grade 7, 92 patients; and grades 8-10, 111 patients) correlated best with outcome. In univariate analysis, this four-tier grouping correlated significantly with local recurrence, distant metastases, any relapse, and survival. The incidences of distant metastasis at 10 years were: grades 2 and 3, 13%; grades 4-6, 34%; grade 7, 52%; and, grades 8-10, 63%. The survival rates at 10 years were: grades 2 and 3, 64%; grades 4-6, 60%; grade 7, 46%; and grades 8-10, 24%. In multivariate analysis, Gleason grade was the single most important determinant of outcome for each endpoint. These results applied equally to needle biopsy and transurethral resection specimens. CONCLUSION: Tumor grade is the single most significant determinant of outcome following radiotherapy for clinically localized prostate cancer. The Gleason system is a valid method for grading tumors to be irradiated. A four-tier grouping into grades 2 and 3, grades 4-6, grade 7, and grades 8-10 appears to be adequate and simple.

Actuarial Analysis↗
PubMed1995

Treatment of osteosarcoma with ifosfamide: comparison of response in pediatric patients with recurrent disease versus patients previously untreated: a Pediatric Oncology Group study.

This study was designed to test if the activity of a phase II agent, ifosfamide, would have been underestimated if it was tested exclusively in a population of children and young adults with recurrent osteosarcoma. The response rate to ifosfamide was compared in patients younger than 30 years of age with previously untreated osteosarcoma with metastases at diagnosis and/or unresectable primary tumors (stratum 1) with that of patients with recurrent osteosarcoma following adjuvant chemotherapy who were not previously exposed to ifosfamide (stratum 2). Evaluation of response was conducted 3 weeks after two courses of ifosfamide (2400 mg/m2 x 5 days) were administered 3 weeks apart. Nine of 33 (27%) evaluable patients in stratum 1 responded (1 complete and 8 partial responses) to ifosfamide. Among 30 evaluable patients in stratum 2, only 3 (10%) responded (1 complete and 2 partial responses; P = .04) Both groups of patients received equal doses of ifosfamide and experienced comparable toxicities. Results from this study suggest that the activity of new agents will be underestimated if tested in a population of heavily pretreated patients with recurrent disease. When possible, new chemotherapeutic agents should be tested in patients with a poor prognosis who have not been exposed to chemotherapy.

Adolescent↗
PubMed1995

Ductal carcinoma in situ treated with lumpectomy and irradiation: histopathological analysis of 49 specimens with emphasis on risk factors and long term results.

Forty-nine women with ductal carcinoma in situ (DCIS) treated with lumpectomy and irradiation were studied retrospectively. The median age was 50 years (range, 29 to 73 years) and the median follow-up time from initiation of therapy was 86 months (range, 17 to 230 months). Twelve patients presented with palpable masses (0.4 to 4 cm), three with breast thickening, and three with nipple discharge. In 31 patients the tumors were detected by mammography. Intraoperatively, excision of lesions was confirmed by specimen x-ray (38 specimens) or gross inspection (five specimens) and was recorded to be complete. No record was available in the other six patients. Margins of excision free of DCIS were microscopically confirmed in 25 specimens. The size of impalpable DCIS lesions recorded in 25 patients ranged from 0.4 to 5.0 cm (mean, 1.5 cm). Using Lagios' classification system, there were 18 classic comedocarcinomas, high nuclear grade (NG) with necrosis; seven cribriform/papillary, high NG with necrosis; 17 cribriform/micropapillary, intermediate NG with or without necrosis; and seven cribriform/micropapillary, low NG without necrosis. In two patients residual malignant calcifications were present on the postoperative mammogram. Disease recurred in the treated breast at the site of incision in five patients at 18 months and 8, 11, and 12 (two patients) years from initial therapy. The rate of local disease recurrence was 2% at 5 years and 6% at 10 years; three recurrences showed invasive ductal carcinoma and two were DCIS. To evaluate risk factors the following characteristics were considered: necrosis, NG, histological type, periductal fibrosis, periductal lymphoid infiltrate, margin status, age, and method of tumor detection. The end points chosen were recurrence and death from any cause (because only one patient died of disease). Although the recurrences were attributed to residual disease in two patients, of the clinical and pathological parameters evaluated, only periductal fibrosis showed a significant relationship with outcome, with a P value < or = .05 by the Wilcoxon test. On the other hand, using the proportional hazards model, necrosis was a significant predictor for recurrence (P = .02), as was the pair fibrosis and tumor detection when taken together (P = .05). Fibrosis significantly associated with high NG, Lagios' histological subtypes I and II, periductal lymphoid infiltrate, and necrosis (P < or = .0006).(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1995

Epstein-Barr virus is detected in undifferentiated nasopharyngeal carcinoma but not in lymphoepithelioma-like carcinoma of the urinary bladder.

The Epstein-Barr virus (EBV) is associated with nasopharyngeal carcinoma (NPC) and with lymphoepithelioma-like carcinomas developing in certain anatomic sites. In this study, an in situ hybridization was used to identify EBV-encoded ribonucleic acid (RNA) (EBER1) transcripts in 32 of 45 cases of NPC but not in any of the 11 lymphoepithelioma-like carcinomas developing in the urinary bladder. EBER1 was most commonly detected in those NPCs having undifferentiated or nonkeratinizing squamous histology rather than the keratinizing squamous cell subtype of NPC. The EBV-encoded latent membrane protein 1 (LMP1) was expressed focally in only seven of 21 EBER1-positive NPCs by an immunohistochemical technique. These findings imply that EBER1 hybridization is more sensitive than LMP1 immunohistochemistry on paraffin sections in detecting carcinoma-associated virus. Previous in vitro studies have suggested that LMP1 expression might be a function of differentiation, but this study of naturally infected NPCs showed no strong correlation between LMP1 positivity and degree of tumor differentiation, albeit a limited spectrum of differentiation that could be examined. In two cases in which frozen tissue was available, the NPCs were monoclonal with respect to viral DNA structure, implying that the virus was present before malignant transformation. Unlike NPCs, the lymphoepithelioma-like carcinomas of the bladder were uniformly EBV negative, lending further evidence to the growing body of literature linking EBV with lymphoepithelial carcinomas of foregut-derived tissues but not with similar-appearing tumors developing in other anatomic sites.

Blotting, Southern↗