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[Laryngeal edema after radiotherapy--radiation reaction or a property of the neoplasm (recurrence, residual neoplasm)].

The authors discuss occurrence of post-radiation laryngeal oedema in the cases of patients with laryngeal cancer. The examination was carried out in 69 cases of patients on whom laryngectomy had been performed after failure of radiotherapy. In 65 out of these cases patients suffered from oedema of larynx with 57 cases classified as persistent or progressive post-radiation oedema (lasting for over three months inspite of application of pharmacological treatment), and 8 cases identified as fluctuating (receding after application of treatment and periodically reoccuring). Analysing the microscopic material of the specimens of the post-radiation oedema, the authors differentiated the stasis, inflammatory oedema and that causes by the presence of cancer infiltration. Basing on their own research data and the contemporary literature, the authors conclude, that the occurrence of persistent post-radiation oedema of the larynx lasting for the three months without reaction to the applied pharmacotherapy should be regarded as an important symptom signalling the presence or the recurrence of tumour after radiotherapy.

Biopsy↗

Photodynamic therapy for residual neoplasms of the perianal skin.

PURPOSE: The aim of this study was to evaluate the efficacy of photodynamic therapy in the management of residual neoplasms of the perianal skin. METHODS: This is a retrospective review. Five patients with pathologic confirmation of residual perianal neoplasms were treated with photodynamic therapy. There were three females. The mean age was 52 (range, 33-79) years. Pathology consisted of Bowen's disease in two patients, squamous-cell carcinoma in two patients, and extramammary Paget's disease in one patient. Four patients received one photodynamic therapy treatment and one patient received two treatments three months apart. RESULTS: Treatment was followed by immediate perianal erythema, subsequent blister formation in 36 to 48 hours, and sloughing of the treated area in 72 hours. With a mean follow-up of 5.2 (range, 1-8) years, there were two recurrences. One recurrence was in a patient four years after treatment for Paget's disease, and the other was in a patient nine months after treatment for Bowen's disease. The latter was managed successfully with wide local excision. Treatment-related toxicities included significant perianal pain in four patients, controlled with analgesia management. CONCLUSIONS: Photodynamic therapy can successfully be used after wide local excision for residual neoplasms of the perianal skin. Treatment can be rendered with acceptable morbidity.

Adult↗

Frequency of residual neoplasm in the prostate following three-dimensional conformal radiotherapy.

The incidence of residual neoplastic cells on prostatic biopsy following conventional external beam radiotherapy is reported to range from 40-90%. As a result, it has been stated that current modalities of radiotherapy may carry an unacceptable local failure rate even in patients irradiated for low stage disease. In order to assess the potential benefits of three-dimensional (3-D) treatment planning, an unselected, consecutive group of patients with localized adenocarcinoma of the prostate was evaluated. This study was designed to determine the frequency of residual cancer in the prostate two years following definitive external beam radiotherapy designed, using a 3-D planning system. Between February 1988 and February 1989, 30 consecutive patients with localized (Stage T1-T3NxMo) adenocarcinoma of the prostate received definitive external beam radiotherapy. All treatment fields were designed with a computed tomography (CT)-based 3-D treatment planning system, resulting in a static conformal radiotherapy plan. The minimum dose delivered to the target volume, which included the prostate, periprostatic tissues, and a 1 cm margin, was between 65 and 69 cGy. Twenty-six patients had Stage T1, T2NxMo primary tumors and four were T3NxMo. Two years following the completion of treatment, all patients underwent digital rectal examination, transrectal ultrasound examination of the prostate with multiple biopsies, bone scan, and serum prostate specific antigen (PSA) determinations. Residual prostate cancer was proven by biopsy in six of 30 patients (20%). Four of 26 (15%) with Stage T1 and T2 tumors had a positive biopsy. However, two of the four Stage T3 tumors had postradiation biopsies positive for cancer (50%). Only one patient with a positive biopsy had an abnormal rectal examination. Five of the eight patients with elevated serum PSA levels after two years had residual neoplasia identified on biopsy. One of six patients with an abnormal postradiation ultrasound had residual tumor. Only one of the 22 patients (5%) with a normal serum PSA at two years had a positive postradiation biopsy. In patients with localized prostate cancer, the use of 3-D static conformal radiotherapy followed by multiple ultrasound guided biopsies confirmed the efficacy of external beam radiotherapy in low stage disease. We believe that the low incidence of positive biopsies in this study resulted from the benefits of 3-D treatment planning as well as the fact that all patients were evaluated, whereas past studies have been in selected patient groups when suspicion of residual disease existed prior to biopsy.(ABSTRACT TRUNCATED AT 400 WORDS)

Adenocarcinoma↗

Low-dose subcutaneous interleukin-2 in patients with minimal residual lymphoid neoplasm disease.

Interleukin-2 (IL-2) is a cytokine that became available for clinical use with the development of recombinant DNA technology. Patients with resistant or relapsed lymphoid neoplasm have been treated with high-dose IL-2 with some responses. The aim of the present study is to determine whether there may be a biological justification for the use of low dose subcutaneous (s.c.) IL-2 as maintenance therapy in patients with lymphoid neoplasm in complete remission with high risk of relapse. We treated 15 patients with sc IL-2, 4.5 Million International Units (MIU) daily, 5 days per week for 12 consecutive weeks, in the outpatient clinic. This therapy was well tolerated and could be administered in an outpatient regimen. It increased the eosinophil count (p = 0.009), but the number of granulocytes, monocytes, T-lymphocytes and B-lymphocytes did not change. The number of natural killer (NK) cells increased from 11% to 35% of all lymphocytes during IL-2 therapy (p = 0.0006). Effector lymphokine-activated killer activity (eLAK) also increased from 6x10(-3) Lytic Units (LU)/ml to 80x10(-3) LU/ml (p = 0.02). All these changes reached a "plateau" after the 4th week of therapy. The increase in the number of NK cells correlated strongly with the increase in eLAK activity (r = 0.96, p<0.0001). Disease-free survival was determined in 14 patients who completed the treatment and compared with historical controls. Patients treated with IL-2 had the same relapse risk (median time to relapse 11.1 months, 95% confidence interval 5.5-16.6) as did controls (median time to relapse 9.7 months, 95% confidence interval 1-27.7) (p = 0.9). Low dose s.c. IL-2 stimulated NK proliferation, which generated cytotoxic activity in vivo in patients with lymphoid neoplasms. However, these patients did not have a lower risk of disease relapse compared to historical controls.

Adolescent↗

Reduced F-18 fluorodeoxyglucose uptake within marrow after external beam radiation.

PURPOSE: The authors examined the delayed effects of external beam radiation on the metabolism of intravertebral marrow cavities. MATERIALS AND METHODS: Two neurologically normal persons who had completed a full course of external beam radiotherapy for squamous cell carcinoma of the head and neck had positron emission tomography (PET) scans with F-18 fluorodeoxyglucose (FDG) to identify residual neoplasm. RESULTS: Abnormally low uptake of F-18 FDG was noted within the central marrow cavities of the cervical vertebral bodies in both cases. CONCLUSIONS: Diminished metabolic activity within irradiated marrow can be revealed by F-18 FDG PET imaging techniques. Further correlative MRI PET studies are needed to determine if this postradiation phenomenon is related to fatty infiltration of the marrow cavity.

Adult↗

Cryosurgery re-visited for the removal and destruction of brain, spinal and orbital tumours.

Advances in neuroimaging and cryosurgical techniques have prompted us to re-evaluate the potential of cryosurgical techniques for the removal and the destruction of various neoplasms. We have used cryosurgical instrumentation to remove tumours in the brain, spine and orbit in 71 patients without complications. Cryosurgery was used to facilitate removal and extraction in 64 and to destroy residual neoplasms when removal was incomplete in 7. Intraoperative real time ultrasonic imaging permitted precise delimitation of tumours from surrounding tissues and allowed monitoring during the production of cryosurgical lesions thus permitting heretofore unavailable visualization of the production of cryogenic lesions in the central nervous system. New cryosurgical instrumentation was used to produce lesions up to three times larger than similar sized probes previously available. Our results reconfirm that cryosurgery facilitates the removal of tumours in the brain, spinal cord and orbit, reduces blood loss in vascular tumours, and is effective in ablating residual neoplasms involving the superior sagittal sinus, torcula and parasagittal areas. A Doppler flowmeter proved useful for monitoring sagittal sinus blood flow during the production of cryosurgical ablation of residual tumour attached to the walls of the sagittal sinus. Recent advances in ultrasonic and neuroimaging coupled with stereotactic techniques and improvements in cryosurgical instrumentation may prove useful in the future percutaneous destruction of selective intracranial neoplasms.

Adult↗

Beneficial effect of combination hormonal therapy administered prior and following external beam radiation therapy in localized prostate cancer.

PURPOSE: The aim of the present study is to investigate whether combined androgen blockade associated with radiation therapy for localized prostate cancer decreases at 12 and 24 months the rate of positive follow-up biopsies and serum PSA compared to radiation therapy alone. This is the report of an interim analysis. METHODS AND MATERIALS: One hundred and twenty patients with clinical Stage B1-T2a, B2-T2b/T2c, and C-T3/T4, adenocarcinoma of the prostate were entered in a prospective randomized study. After written informed consent, the subjects were randomly allocated between external beam radiation therapy (EBRT) alone (group 1), 3 months of neoadjuvant combination therapy (LHRH-agonist + Flutamide) prior to EBRT (group 2), and a third group receiving combination therapy 3 months before, during, and 6 months after EBRT. There is no significant difference between the three groups concerning age, stage of disease, grade of tumor, and pretreatment PSA levels. Control transrectal ultrasound (TRUS)-guided needle biopsies (one core was taken from the initial cancer site regardless of the presence or absence of TRUS abnormalities) were done 12 and 24 months after the end of EBRT. Serum PSA measurements were done on schedule visits. RESULTS: Ninety-two and 68 patients underwent biopsies at 12 and 24 months, respectively, after the end of radiation therapy. While 62% of control patients at 12 months in Group 1 disclosed residual neoplasm, only 30% and 4% showed residual disease in groups 2 and 3, respectively (p = 0.00005). When looking at 24 months, 65, 28, and 5% showed residual cancer for groups 1, 2, and 3, respectively (p = 0.00001). The PSA measurements indicate also at 12 months a difference between the three groups (p < 0.0001), except at 24 months, the difference between the group 2 and 3 is no longer significant. CONCLUSION: The preliminary analysis of this clinical trial indicates that patients treated with radiation therapy alone show a significantly higher rate of positive biopsies at 12 and 24 months after the end of radiation therapy as compared with those treated with total antiandrogen blockade (TAB) and radiation therapy. When analyzing the median PSA serum levels, we found the same advantage at 12 months, but, at the time of the analysis at 24 months, the PSA levels are not different between groups 2 and 3.

Aged↗

Pharyngography after head and neck irradiation: differentiation of postirradiation edema from recurrent tumor.

OBJECTIVE: In patients previously irradiated for head and neck carcinomas, persistent soft-tissue thickening in the larynx and pharynx makes it difficult to distinguish between postirradiation edema and recurrent epidermoid carcinoma. The goal of this work was to characterize the standard double-contrast pharyngographic appearance after irradiation and to differentiate this appearance from that of recurrent or residual neoplasms. MATERIALS AND METHODS: The posttreatment pharynogograms in 43 patients treated with radiotherapy for malignant tumors of the head and neck were retrospectively reviewed. The pharynx had been included in the radiation field in each case. We characterized the posttherapy appearance and identified radiographic signs that could be used to distinguish normal postirradiation edema from recurrent tumor. RESULTS: Soft-tissue thickening of normal laryngeal and pharyngeal structures and laryngotracheal aspiration were common nonspecific findings on posttherapy pharyngograms, each occurring in 39 of 43 patients. Epiglottic enlargement and laryngotracheal aspiration did not correlate with the presence of residual or recurrent neoplasm. Asymmetric swelling was more common ipsilateral to the original neoplasm and did not necessarily indicate a malignant tumor. Mucosal irregularity, ulceration, and a demonstrable focal mass were the only significant predictors of recurrent or residual tumor; at least one of the three findings was present in 17 of 19 patients with neoplasm correctly identified by pharyngography. CONCLUSION: Double-contrast pharyngography is a useful means of diagnosing pharyngeal tumors in patients who have had radiation therapy. Radiographic signs of neoplasm (ulcer, mucosal irregularity, and a focal mass) can be used to distinguish recurrent tumor from nonmalignant changes after irradiation.

Aged↗

Fetal rhabdomyomatous nephroblastoma.

A case of fetal rhabdomyomatous nephroblastoma is reported. The neoplasm distended the renal pelvis, resembling a sarcoma botryoides. The patient died postoperatively of pneumonia and an autopsy showed no residual neoplasm.

Child, Preschool↗

Cytology of metastatic neuroendocrine (Merkel-cell) carcinoma in pleural fluid. A case report.

A case of Merkel-cell (neuroendocrine) carcinoma of the skin with extensive metastases, including pleural effusion, occurring over 20 years after primary resection and treatment, is reported. The histologic appearance of the primary neoplasm was identical to that seen in the biopsy specimens of the metastatic carcinoma involving the great toe and inguinal lymph nodes and to that of the residual neoplasm tissue found at necropsy. Electron microscopic examination of a lymph node metastasis demonstrated cytoplasmic microfilaments and numerous dense-core, peripheral, neurosecretory granules, as previously described in Merkel-cell carcinoma. Cytologic examination of a pleural fluid specimen demonstrated numerous small malignant cells closely resembling the cells seen in the histopathologic sections from the surgical and necropsy tissues involved by metastatic carcinoma. This is the first report of the cytologic findings in a patient with Merkel-cell carcinoma metastatic to the pleural cavity.

Carcinoma, Small Cell↗

Combined chemotherapy and surgery in treatment of advanced germ-cell tumors.

Forty-eight selected patients with GCT who were suspected of having residual disease after two or three chemotherapy inductions underwent an attempt at resection of this residual tumor. In 37 patients all gross disease was resected: 11 had malignant tissue, eight adult teratoma, and 18 no residual neoplasm, and 9, 7 and 17, respectively, remain free of disease. Patients in whom complete resection was not possible generally did poorly. Elevated serum tumor markers following the completion of preoperative chemotherapy indicated residual malignant disease and poor probability for complete resection. Twenty-nine percent of patients with negative preoperative markers had malignancy at the time of surgery, but disease was resectable in most of these patients. The key for success is, first, the response to chemotherapy and, second, complete resection of residual disease. It is recommended that patients with initially bulky metastases (diameter greater than 5 cm) be first managed by chemotherapy, employing successive close inductions, and subsequently explored with intent to resect residual disease. When the resected specimen shows malignant elements, the patients should receive additional inductions, otherwise, maintenance chemotherapy is employed.

Antineoplastic Agents↗

Long-term prognostic value of detection of circulating colorectal cancer cells using CGM2 reverse transcriptase-polymerase chain reaction assay.

BACKGROUND: The criteria commonly used for prognosis of colorectal cancer remain histoprognostic and are based on primarily TNM classification. The lack of discrimination of purely histoprognostic criteria is evidenced by the development of different outcomes in similarly staged patients. The aim of this work was to study the long-term prognostic value of preoperative detection of circulating enterocytes in the blood of colorectal cancer patients using the CGM2 reverse transcriptase-polymerase chain reaction (RT-PCR) assay. METHODS: A nested RT-PCR with specific primers for CGM2 was used preoperatively to detect circulating enterocytes in 121 patients (64 men, 57 women; mean age, 70 years) with colorectal neoplasms. RESULTS: Circulating enterocytes were detected in 58/121 (48%) patients. The positivity rate was not correlated with American Joint Committee on Cancer (AJCC) staging (stage I, 11/28 (39%); stage II, 13/34 (38%); stage III, 15/23 (65%); stage IV, 17/32 (53%); sterilized (after radiotherapy, no residual neoplasm) 2/4 (50%); not significant [NS]), but circulating enterocytes were detected more frequently in patients with metastatic lymph nodes (60% vs 41%, P = .06). Overall 5-year survival rates (mean +/- SD) were 40 +/- 13% and 45 +/- 13% for patients without and with circulating enterocytes, respectively (P = NS). Similarly, recurrence-free survival rates were 71 +/- 4% versus 72 +/- 14% (P = NS). Using univariate analysis, AJCC stage (P < .0001) was correlated with survival. AJCC stage (P = .007) and obstructive neoplasms (P = .043) were correlated with recurrence-free survival. Using multivariate analysis, AJCC stage was correlated with survival and recurrence-free survival. CONCLUSIONS: Preoperative detection of circulating enterocytes using CGM2 RT-PCR assay provides no specific prognostic information and cannot be used as a decision criterion for adjuvant therapy.

Actuarial Analysis↗

The value of mammography after limited breast surgery and before definitive radiation therapy.

One hundred twenty consecutive patients who had breast-conserving surgery for cancer and were referred for definitive radiation therapy (RT) had a mammogram performed before starting RT. This was done to determine the presence of residual neoplasm or other abnormalities that may alter or delay the planned RT and are undetected by other means. It also was performed to provide a baseline for the diagnosis of postoperative changes and recurrence of disease on follow-up studies. In six (5%) patients, calcifications or masses were found that proved to be residual tumors. This led to reexcision in two, mastectomies in two, and a higher radiation booster dose to the tumor bed in two. Eight (6.6%) patients had postoperative hematomas larger than 4 cm in diameter, which delayed the start of RT by 2 to 3 weeks. In 39 (32%) patients, the pre-RT mammogram provided information considered to be helpful for the interpretation of post-RT mammograms. Such information may lead to a decrease in the number of diagnostic biopsies based on indeterminate mammographic findings. Therefore, a routine mammogram is recommended before RT is started.

Adult↗

The clinical and radiological evaluation of primary brain neoplasms in children, Part II: Radiological evaluation.

Data collected over the past 8 years on the radiological appearance of common pediatric primary brain neoplasms are presented. An emphasis is placed on the newer radiological imaging modality of magnetic resonance imaging (MRI). Part I of this article emphasized the clinical evaluation of these brain neoplasms. Three hundred eighty-five children with known brain neoplasms ranging in age from newborn to 18 years were evaluated with one or all of the following radiological modalities: MRI, computed tomography (CT), water-soluble myelography (WSM), WSM with CT, and angiography. Contrast-enhanced MRI and CT scans both were accurate in delineating these brain neoplasms although MRI provided better resolution and delineation than CT. Angiography provided information on the vascularity of the neoplasms and their relationship to prominent arterial and venous structures. Water-soluble myelography with CT and gadolinium-enhanced MRI of the spine were equally accurate in demonstrating metastatic spread to the spinal canal and spinal cord. Magnetic resonance imaging with gadolinium was more accurate than CT with contrast in demonstrating recurrent or residual neoplasm at the operative site and metastatic spread to the brain. Magnetic resonance imaging with gadolinium is the best radiological modality to fully evaluate pediatric brain neoplasms.

Brain↗

Primary mediastinal malignant germ cell neoplasms: imaging features.

Mature teratomas are the most frequent primary mediastinal GCN. These are spherical multilocular cystic masses with thin, soft tissue septa and frequent internal fat attenuation. Primary mediastinal malignant GCNs are rare and should be included in the differential diagnosis of anterior mediastinal masses in young adult males. Seminomas are typically homogeneous masses indistinguishable from lymphomas. Radiologically nonseminomatous malignant germ cell neoplasms are large, locally invasive heterogeneous masses with central low-attenuation and frond-like peripheral soft tissue. Gonadal primary malignancy and intervening abdominal lymph node involvement should be excluded. Tumor markers play a crucial role in the initial evaluation of anterior mediastinal masses in these patients and in evaluating response to therapy and possible recurrence. Follow-up imaging is helpful in detection and characterization of residual neoplasm.

Adult↗

[Treatment with L-thyroxine for differentiated thyroid carcinoma].

Differentiated thyroid carcinoma (DTC) is one of malignant neoplasms with a very good prognosis and low mortality rate provided a proper therapy and its systematic monitoring is given. DTC treatment consists of surgery, radioiodine and L-thyroxine therapy. L-thyroxine therapy in DTC should be both substitutive and suppressive. Substitutive therapy consists in the removal of the lack of thyroid hormones symptoms so that the serum TSH is about 1 mU/l. Suppressive therapy consists in complete inhibition of TSH secretion by pituitary gland. This prevents from the regrowth and inhibition of carcinoma progress in patients with evident or residual neoplasmic disease. Although complete suppressive therapy (TSH less than 0.05 mU/l) is the most recommended one, in patients with low recurrence risk incomplete suppression can be used (TSH = 0.1-0.3 mU/l). Suppressive L-thyroxine doses may give side-effects such as: cardiac signs (arrhythmia, coronary or heart insufficiency), decrease in bone mineral density with osteopoenia or osteoporosis or subclinical hyperthyroidism. However, the side-effects of the suppressive L-thyroxine doses may be symptomatically treated (with beta-blockers, biphosphoniates).

Cardiovascular Diseases↗

Surgical treatment of spinal ependymoma and post-operative radiotherapy.

INTRODUCTION: With the advances in microsurgical and monitoring techniques, spinal ependymomas are gross totally resected more frequently. The use of adjuvant radiotherapy has become questionable with gross total resection and its role for residual neoplasm need to be redefined. A retrospective analysis of a series of patients was carried out to investigate our clinical outcome and selected use of post-operative radiotherapy. CLINICAL MATERIALS AND METHODS: Between July 1990 and May 1995, nineteen patients [M : F = 12 : 7; age range: 21 to 71 years] with a spinal ependymoma were treated at University of Miami by the senior author. (BAG) Pre-operative MRI diagnosed the intraspinal tumor, and pathology reports demonstrated that each patient had a histologically confirmed ependymoma. At the time of diagnosis, the most common symptoms presented were pain (in 16 patients = 84.2%). The pattern of progression of clinical symptoms was directly related to the location of the tumor. Each patient had an MRI immediately after surgery, approximately 6 months post-operatively, and then annually. RESULTS: All 19 patients underwent intradural microsurgical exploration with an attempted gross total resection (achieved in 16 patients = 79%) of the ependymoma through a posterior approach. Direct neural tissue stimulation halted further resection in 2 patients with questionable tumor margins. Radiation therapy was employed as a surgical adjunct in 3 patients (15.8%) because of possible residual tumor. All patients were followed up postoperatively for an average of 50.6 months (range 6 months to 6 years). All patients are surviving to date. Surgical resection of these tumors led to significant alleviation of pre-operative symptom. There has been no radiographic evidence of tumor recurrence or growth in any patient to date. CONCLUSION: Surgical resection of spinal ependymoma leads to significant improvement of pre-operative symptoms. Surgical removal alone, with an attempt to grossly resect the tumor, should be the treatment of choice, with careful clinical and radiographic follow-up. Radiation therapy should only be considered as a surgical adjunct where gross total resection is not achieved.

Adult↗

Pathologic findings from the National Surgical Adjuvant Breast Project (NSABP) eight-year update of Protocol B-17: intraductal carcinoma.

BACKGROUND: This report is an 8-year update of the authors' previous findings from National Surgical Adjuvant Breast Project (NSABP) Protocol B-17, which relates to the influence of pathologic characteristics on the natural history and treatment of intraductal carcinoma (DCIS). METHODS: Nine pathologic features observed in a pathologic subset of 623 of 814 evaluable women enrolled in this randomized clinical trial were assessed for their role in the prediction of second ipsilateral breast tumors (IBT), other events, and selection of breast irradiation (XRT) following lumpectomy. RESULTS: The frequency of subsequent IBT was reduced from 31% to 13% (P = 0.0001) by XRT. The average annual hazard rates for IBT were reduced by XRT for all pathologic features examined. Four characteristics were individually noted to be significantly related to IBT, but only moderate-to-marked and absent-to-slight comedo necrosis were found to be independent high and low risk predictors, respectively, for such an event in patients of both treatment groups. XRT effected a 7% absolute reduction at 8 years in the low risk group. Despite a relatively high incidence (approximately 40%) of IBT consisting of invasive cancer, mortality due to breast carcinoma after DCIS for the entire cohort was found to be only 1.6% at 8 years. CONCLUSIONS: The degree of comedo necrosis in patients with DCIS appears to be sufficient for discriminating between high and low risks for IBT following lumpectomy for DCIS. Although margin status, unlike in our previous report, was found to have only a slight or borderline influence on the frequency of IBT at 8 years, excision of DCIS with free margins is advised. The low risk group exhibits a statistically significant reduction of IBT from XRT. The decision to forgo XRT in the treatment of this singular subset of patients would appear to depend on clinical considerations and the input of informed patients rather than being standard practice. [See editorial on pages 375-7, this issue.]

Breast Neoplasms↗