Brain stem gliomas: therapeutic options at time of recurrence.
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A 27-month-old girl presented with chest pain. Further evaluation confirmed posterior mediastinal neuroblastoma with bone marrow infiltration, which was treated with a combination of chemotherapy and surgery. Four months after completing treatment, she presented with myoclonus and weakness of her right arm. The myoclonus eventually subsided but her right arm weakness progressed to a right hemiplegia. High titers of antineuronal nuclear antibodies identified as anti-Hu were found in both serum and cerebrospinal fluid. One month later she presented with a relapse of her original tumor, from which she died. Identification of anti-Hu antineuronal nuclear antibodies in this neuroblastoma-associated paraneoplastic syndrome supports the hypothesis that the syndrome is due to autoimmune disease.
We report case of a patient with hypopharyngeal biphasic sarcomatoid carcinoma, with two tumor cell component, epidermoid and spindle cells, treated by surgery only. Two years later, recurrence is noted with totally different histologic form, sarcomatous monophasic, with spindle tumor cells and smooth muscle phenotype with immunohistochemistry, looking like primitive leiomyosarcoma of high malignancy degree. Such monophasic sarcomatous forms of sarcomatoid carcinoma, without epithelial tumor component, are deceptive and can be mistaken with primitive sarcoma. That is why discovery of epithelial differenciation signs, with immunohistochemistry or electronic microscopy, is very important. In our case, while the epithelial differenciation in the recurrent tumor is away, previous history of true biphasic sarcomatoid carcinoma in the same anatomic location, allows to assert recurrence of the same tumor with monophasic sarcomatous expression and smooth muscle phenotype in this case. Therefore in front of "sarcoma of the upper aerodigestive tract", of any immunohistochemical phenotype, monophasic sarcomatous form of epidermoid sarcomatoid carcinoma have always to be evocated and searched.
OBJECTIVE: To present a review of literature and to analyse a clinical retrospective series of patients with granulosa cell tumor. DESIGN: Retrospective study and review. SETTING: Department of Obstetrics and Gynaecology, First Faculty of Medicine, Prague, Czech Republic. METHODS: Retrospective analysis of age, stage, surgery, radiotherapy and chemotherapy, survival curve, number of recurrences and time to recurrence. Literature and information database (Medline 1997-1999) review. RESULTS: In a group of 43 patients the median of age was 53.5 years. 83.7% of cases were in a stage I. There were two duplicate tumors in a series. Conservative surgery was performed in 9/43 cases, 5 of them were reoperated on. The most frequent chemotherapy regimens were platinum-cyclophoshamide and BEP (bleomycin, etoposide, platinum). The 5-year overall survival was 86% and specific survival 90.7%. There were 3/43 recurrences, median time to recurrence was 22 months. CONCLUSION: A good prognosis of a patient with granulosa cell tumor requires a precise histopathologic examination, an adequate surgery and a comprehensive clinical analysis of a case to evaluate an indication of adjuvant therapy. Concentration of patients in oncogynaecological centres is advisable. A careful follow-up because of a risk of late recurrences is necessary.
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Comparative evaluation of different surgical approach for the treatment of pterygium with the respect on recurrence, time interval to the recurrence and postoperative complications is done. Only 6% of recurrence were found using buccal mucosal flap as the first surgery, but when the same approach is used for recurrence number of retreatment is similar to the other technique-transpositional slide flap. 5-Fluorouracil as additional therapy decreased the number of recurrence without increasing of complications.
The effects of prognostic factors on local, regional or distant metastasis are standardly assessed separately. Competing risks analyses may be used to assess simultaneously the effects of factors on different types of first recurrence. Data for a cohort of 678 primary invasive breast cancer patients accrued between 1971 and 1990, updated to 1995, included type of first recurrence (local, regional, distant). We investigated the effects of the traditional factors of age, tumour size, nodal status, ER, PgR, adjuvant therapy (hormones, chemotherapy, radiotherapy) on type of recurrence and time to recurrence for all patients and for those aged > or = 65. For all ages of patients, there were five factors with significant associations with type or time to first recurrence. Adjuvant radiation was the only factor which had an effect (P < or = 0.05) on the type of first recurrence: being associated with a reduction in local recurrence. Age, nodal status, tumour size and adjuvant chemotherapy all had significant associations across all types of first recurrence, and in particular with time to recurrence for both local and distant metastasis. This indicates a potential lack of independence in these end-points. For patients > or = 65 years of age, there were no factors which differentially affected type of recurrence, while only nodal status and tumour size had significant associations with time to recurrence. Analyses were used to assess simultaneously the effects of traditional prognostic factors and treatment options on type of first recurrence and time to first recurrence. The extension to evaluations with newer prognostic factors would expedite the determination and mode of biologic activity for such factors.
Gallstone recurrence was evaluated in 184 patients exhibiting complete stone disappearance after successful extracorporeal shock-wave lithotripsy (ESWL) and concomitant oral bile acid therapy. Follow-up examinations conducted 6-43 months after termination of adjuvant bile acid therapy revealed recurrent calculi in 40/184 (21.7%) patients (27 females, 13 males, p < 0.01; 13 patients with solitary, 27 patients with multiple stones) after a median stone-free period of 11 months (range 1-33 months; mean +/- SD, 13 +/- 8 months). Therefore, an overall probability of stone recurrence of 11.8% was observed 12 months after complete stone disappearance had been confirmed sonographically and bile salt therapy terminated, and a probability of 25.5% after 24 months. Gallstone reformation occurred in 30/146 (20.5%) patients with initially solitary and 10/38 (26.3%) patients with multiple calculi [not significant (NS)]. Only 3/40 (8%) patients with recurrent calculi reported biliary colic. Sonographic gallbladder contractility values acquired at the time recurrent stones were detected did not show any significant differences, compared with the data obtained in the pretreatment examinations; neither were any differences noted between the patients with gallstone reformation and those who remained stone-free. In 20/33 (61%) patients with recurrent stones who opted for further conservative retreatment (ESWL and/or oral litholysis), complete stone disappearance was achieved a second time. The recurrence rates achieved within the first 3 yr after successful shock-wave lithotripsy of biliary calculi cover a range similar to the rates noted after dissolution therapy.
From November 1977 to July 1987, 300 consecutive patients with endometrial carcinoma clinically confined to the uterine corpus underwent primary surgery consisting of at least abdominal hysterectomy and adnexectomy. Patients with aggressive disease characteristics received postoperative radiotherapy. Forty-seven patients (16%) demonstrated recurrent disease from 2 to 125 (median of 12.8) months after surgery. Forty-seven percent of the recurrences were detected within the first year following surgery and 70% by 2 years after hysterectomy. Of the 47 recurrences, 29 were at distant sites, 16 were within the pelvis, and 2 consisted of both local and distant recurrences. Patients treated with pelvic radiotherapy after hysterectomy were more likely to experience distant, rather than local recurrences. Only 7 of the 148 patients (5%) treated with postoperative radiotherapy recurred in the pelvis. Approximately half of the recurrences were detected in asymptomatic individuals; physical examination and chest X-ray were the most useful means to detect disease in patients without symptoms. The combination of history, physical examination, pap smear, and chest X ray detected all of the recurrences. Actuarial survivals at 12, 24, and 36 months after recurrence were 42, 24, and 17%, respectively. The site of recurrence, time interval of surgery to recurrence, and use of postoperative pelvic radiotherapy were statistically related to patient prognosis. The identification of patients at risk of recurrence and more effective adjuvant therapy need to be developed in order to decrease the frequency of recurrence. In order to substantially improve the survival of patients with recurrent disease, more sensitive methods of detection, as well as more effective salvage therapy, will be required.
BACKGROUND: The natural course of recurrence after bronchoplastic procedures for non-small cell lung cancer (NSCLC) has not been described. METHODS: Sex, age, tnm-stage, histology, neoadjuvant chemotherapy, disease-free interval (months), exact localisation of tumour recurrence, time between first and second recurrence (months), survival after first and second recurrence (months), causes of death were retrospectively recorded in 83 patients operated between December 1993 and July 2001. RESULTS: One patient was lost to follow-up, five resections were nonradical. Survivors' follow-up lasted 5 to 100.7 months (mean 43.3). Fourteen patients (14.4%) died tumor free. Eleven (13.2%) distant recurrences were diagnosed 1 to 42 months (mean 10.6) postoperatively, eight (9.6%) died 0 to 17 months (mean 7.55) after diagnosis. Nine local recurrences (10.8%)-5 unifocal, 4 multifocal-occurred 2 to 35 months (mean 17.3) postoperatively, eight died 0 to 8 months (mean 2.13) after diagnosis. Nine mixed recurrences (10.8%)-1 synchronous, 8 metachronous-were found (14.8%) 2 to 21 months postoperatively (mean 8.3). All died 4 to 41 months (mean 17.83) after diagnosis. Fourteen mediastinal lymph node recurrences occurred, ten as a primary recurrence and four as secondary. Lymph nodes were involved in all multifocal recurrences. Intrabronchial recurrence was observed in five patients and was always a result of progressive regional lymph node recurrence. CONCLUSIONS: The pattern and natural history of recurrence cannot be sufficiently explained by stage and surgical radicality and suggest different genetic characteristics of the primary tumor. In case of reoperation due to intrabronchial recurrence adjuvant mediastinal irradiation should be considered.
Twelve cases of low-grade fibromyxoid sarcoma are presented. The patients' ages ranged from 6 to 51 years; all but three were between 26 and 46 years of age. The tumor was located in the thigh or inguinal area in four patients, in the shoulder area in three patients, and in the axilla-chest wall area, the perineum, the small bowel mesentery, the neck, and the buttock in one patient each. Tumor size (maximum dimension) varied from 3.5 to 15 cm in the nine cases in which it was known (median, 9.5 cm). Histologically, the neoplasms demonstrated contrasting fibrous and myxoid areas, a swirling, whorled growth pattern (at least in part), and bland, deceptively benign-appearing fibroblastic spindle cells; cellularity was low to moderate, mitotic figures were uncommon, and nuclear pleomorphism was usually absent or slight. Focal histologic findings in a minority of the cases included increased perivascular cellularity, moderate nuclear pleomorphism (more often in recurrent tumors), and, in myxoid areas, a rich capillary vascular network (vascularity was usually not prominent). On follow-up, nine patients experienced local recurrence (from one to numerous times); recurrence was subsequently controlled in five cases but not in the remaining four. Distant metastasis occurred in seven cases, chiefly to the lungs, but two of these patients were rendered tumor-free (to latest follow-up) by excision of metastases. At latest follow-up, four patients had died of tumor at 8, 9, 31, and 31 1/2 years, respectively, three were alive with recurrent or metastatic tumor at 6 1/2, 12 1/2, and 50 years, respectively, and five were alive and tumor-free at 5 1/2, 10 1/2, 12, 22 1/2, and 44 years, respectively. One tumor, in the patient who died at 31 years, demonstrated "dedifferentiation" at 30 years. Low-grade fibromyxoid sarcoma is a distinctive, indolent soft-tissue sarcoma.
BACKGROUND: Predicting the behavior of meningiomas based on histopathologic features alone has remained problematic. DESIGN: This study retrospectively compared several histopathologic features and MIB-1 labeling indices (LIs) in recurrent meningiomas with those of nonrecurrent meningiomas. Six histopathologic features, including mitoses, necrosis, loss of architectural pattern, hypervascularity/hemosiderin deposition, prominent nucleoli, and nuclear pleomorphism, were compared between 32 recurrent and 27 nonrecurrent meningiomas using Fisher exact tests. MIB-1 LIs (% positive tumor cell nuclei) were compared using the Wilcoxon rank sum test. RESULTS: The patients in the recurrent group included 26 women (mean age, 55 years), who developed 1 to 5 recurrences. Time intervals to the first recurrence ranged from 5 to 183 months (mean, 55 months). The nonrecurrent group included 21 women (mean age, 56 years), with follow-up ranging from 88 to 124 months (mean, 109 months). Of the histopathologic features evaluated, statistically significant differences between the recurrent and nonrecurrent groups were found only with respect to prominent nucleoli (P =.024) and nuclear pleomorphism (P <.001), both of which were more common in the recurrent group. In the recurrent group, 9 tumors were considered malignant (defined by brain invasion or metastasis) versus 2 of the nonrecurrent meningiomas. Nineteen percent of nonrecurrent tumors versus 41% of recurrent tumors had 2 or more of the 6 histopathologic features. MIB-1 LIs in the nonrecurrent group ranged from 0 to 8.3 (mean, 1.5) and were generally lower than those in the recurrent group (range, 0-32.5; mean, 5.4); no statistical difference was identified between these groups. No statistically significant difference with regard to histology or MIB-1 LIs was noted between the initially excised recurrent tumor and the most recently resected recurrence. CONCLUSIONS: Of the histopathologic features examined, only prominent nucleoli and nuclear pleomorphism were found to be statistically more common in recurrent than nonrecurrent meningiomas. The mean MIB-1 LI was higher in the recurrent than in the nonrecurrent group, although there was no statistical difference between means and there was clear overlap with regard to MIB-1 LI ranges.
AIMS AND BACKGROUND: The main characteristic of urothelial bladder cancer is a clear predisposition to recurrence and disease progression. The aim of this study was to assess the possible relationship between cyclooxygenase-2 (COX-2) immunoreactivity in superficial urothelial bladder carcinoma and tumor grade, stage, number of recurrences and clinical disease progression. METHODS: In this prospective study 70 consecutive patients who underwent transurethral resection for superficial urothelial bladder cancer were included. Tumor slides were immunohistochemically stained for COX-2, and COX-2 immunoreactivity in tumor and inflammatory stromal cells was categorized as negative or mildly, moderately or strongly positive. Patients were followed up for 2 years, and during this period the possible association of COX-2 immunoreactivity with tumor stage and grade, number of recurrences and progression of disease was evaluated. RESULTS: COX-2 immunoreactivity in tumor cells was found in 57 (81.4%) patients and did not correlate with tumor grade, stage of disease, number of recurrences, and progression of disease. COX-2 immunoreactivity in inflammatory cells was found in 16 of the 57 patients with COX-2 positive tumors, and was significantly related to the number of recurrences, time to appearance of the first recurrence, and disease progression. CONCLUSIONS: COX-2 immunoreactivity in inflammatory stromal cells adjacent to the COX-2-positive tumor might be useful in clinical practice for selection of patients with a high risk of tumor recurrence and disease progression.
A retrospective analysis of 877 patients who had malignant melanoma of the head and neck identified 366 patients who developed recurrent disease. Sex, race, age, histology, Clark level, thickness, ulceration, lymph node status, lymph node dissection, site of recurrence, and time to recurrence were analyzed to determine their effect on survival following the development of recurrent disease. Survival following the development of recurrence was found to be influenced by the site of first recurrence and the age of the patient at the time of recurrence. For a given age, patients who had initial recurrences at distant sites were three times as likely to die following recurrence than patients with local recurrence. Patients who had initial recurrences at distant sites were twice as likely to die following recurrence than patients with regional sites of recurrence (p less than 0.001).
This paper presents numerical studies of applying back-propagation learning to a delayed recurrent neural network (DRNN). The DRNN is a continuous-time recurrent neural network having time delayed feedbacks and the back-propagation learning is to teach spatio-temporal dynamics to the DRNN. Since the time-delays make the dynamics of the DRNN infinite-dimensional, the learning algorithm and the learning capability of the DRNN are different from those of the ordinary recurrent neural network (ORNN) having no time-delays. First, two types of learning algorithms are developed for a class of DRNNs. Then, using chaotic signals generated from the Mackey-Glass equation and the Rössler equations, learning capability of the DRNN is examined. Comparing the learning algorithms, learning capability, and robustness against noise of the DRNN with those of the ORNN and time delay neural network, advantages as well as disadvantages of the DRNN are investigated.
BACKGROUND: Intravesical chemotherapy (i.e., placement of the drug directly in the bladder) with mitomycin C is beneficial for patients with superficial bladder cancer who are at high risk of recurrence, but standard therapy is empirically based and patient response rates have been variable, in part because of inadequate drug delivery. We carried out a prospective, two-arm, randomized, multi-institutional phase III trial to test whether enhancing the drug's concentration in urine would improve its efficacy. METHODS: Patients with histologically proven transitional cell carcinoma and at high risk for recurrence were eligible for the trial. Patients in the optimized-treatment arm (n = 119) received a 40-mg dose of mitomycin C, pharmacokinetic manipulations to increase drug concentration by decreasing urine volume, and urine alkalinization to stabilize the drug. Patients in the standard-treatment arm (n = 111) received a 20-mg dose without pharmacokinetic manipulations or urine alkalinization. Both treatments were given weekly for 6 weeks. Primary endpoints were recurrence and time to recurrence. Treatment outcome was examined by use of Kaplan-Meier analysis with log-rank tests. Statistical tests were two-sided. RESULTS: Patients in the two arms did not differ in demographics or history of intravesical therapy. Dysuria occurred more frequently in the optimized arm but did not lead to more frequent treatment termination. In an intent-to-treat analysis, patients in the optimized arm showed a longer median time to recurrence (29.1 months; 95% confidence interval [CI] = 14.0 to 44.2 months) and a greater recurrence-free fraction (41.0%; 95% CI = 30.9% to 51.1%) at 5 years than patients in the standard arm (11.8 months; 95% CI = 7.2 to 16.4 months) and 24.6% (95% CI = 14.9% to 34.3%) (P =.005, log-rank test for time to recurrence). Improvements were found in all risk groups defined by tumor stage, grade, focality, and recurrence. CONCLUSIONS: This study identified a pharmacologically optimized intravesical mitomycin C treatment with statistically significantly enhanced efficacy.