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Localization of pheochromocytoma by selective venous catheterization and assay of plasma catecholamines.

The diagnosis of pheochromocytoma rests primarily on determination of the 24-hour urinary excretion of catecholamines and their metabolites. In most cases nephrotomography and selective arteriography or venography, or both, are sufficient to localize the tumour. Selective venous catheterization and the assay of plasma catecholamines should be considered for pheochromocytoma localization in: (a) patients in whom standard techniques fail to localize the tumour; (b) patients who exhibit idiosyncratic reactions to the angiographic contrast materials; (c) young patients or patients with familial pheochromocytoma, including those with multiple neurofibromatosis or multiple endocrine adenomatosis, type 2; (d) patients with recurrent, malignant, or suspected multicentric or extra-adrenal tumours; and (e) patients excreting only norepinephrine in the urine. The validity of the results is particularly dependent on the skill with which venous catheterization is carried out.

Adrenal Gland Neoplasms↗

[Diagnosis and therapy of incidental renal cell carcinoma].

Renal cell carcinoma (RCC) especially incidentally found RCC has been markedly increased in the world due to development of ultrasound or computerized tomography (CT) instruments. Controversy existed on the nephron sparing treatment for incidental RCC. We have operated the incidental RCC using a technique of tumor enucleation shelling out with 5 mm normal surrounding parenchyma. It is important to demonstrate its pseudocapsule for indication of the procedure. For the purpose MRI (T2) is the most reliable method in comparison with angiography, CT and ultrasound. In 42 cases of incidental RCC, 22 cases were nephrectomized and 19 cases were enucleated. One was not operated on. In our cases there was no local recurrence, metastasis or impaired renal function for over one year. However, some problems still remain such as local recurrence (0% approximately 10%), multicentricity (7%) and residual renal function in the literature. Therefore, we propose the following 4 points for indications of tumor enucleation, (1) asymptomatic completely and incidentally, (2) < or = 4 cm in diameter, (3) stage 1 (T1, T2) with pseudocapsule, (4) peripheral location.

Carcinoma, Renal Cell↗

A phase II study of a paclitaxel and oxaliplatin combination in platinum-sensitive recurrent advanced ovarian cancer patients.

PURPOSE: A multicentric, phase II study to evaluate the efficacy and safety of the combination paclitaxel and oxaliplatin in patients with platinum-sensitive recurrent ovarian cancer. PATIENTS AND METHODS: Patients received 175 mg/m(2) paclitaxel (over 3 h) followed by 130 mg/m(2) oxaliplatin (over 2 h) every 21 days for up to nine cycles without hydration or primary granulocyte colony-stimulating factor prophylaxis. Patients had to have an Eastern Cooperative Oncology Group performance status of 0-2 and to have received no more than one prior cisplatin- and/or carboplatin-containing chemotherapy regimen with a platinum-progression-free interval > or =6 months. RESULTS: Of the 105 patients enrolled and treated, 98 were eligible. An overall response rate of 81% (79 of 98 patients) (95% confidence interval 71% to 88%) was observed according to RECIST criteria (third party reviewed), and 88% (86 of 98) when this was complemented with CA-125 response. With a median follow up of 43.6 months (range 30.2-64.2) the median progression-free survival was 10.2 months (range 0.3-21.4) and the overall survival 32.4 months. Seven hundred and eight cycles were administered (median seven per patient; range one to nine). A total of 67% of patients experienced National Cancer Institute Common Toxicity Criteria grade 3-4 neutropenia, including 8% with concomitant febrile episode, without treatment-related deaths. Ninety-three per cent of patients experienced neuropathy of grade 1 or more, including 25% with cumulative reversible peripheral neuropathy of grade 3-4. Oxaliplatin doses were reduced in 30 patients due to neurotoxicity. CONCLUSIONS: The oxaliplatin/paclitaxel combination can be administered in an outpatient setting every 3 weeks without specific measures. The high level of activity and its duration observed warrants further evaluation of this combination in pretreated platinum-sensitive advanced ovarian cancer patients.

Adult↗

Randomised trial of hyperthermia as adjuvant to radiotherapy for recurrent or metastatic malignant melanoma. European Society for Hyperthermic Oncology.

The value of hyperthermia as an adjuvant to radiotherapy in patients with malignant melanoma was studied in a European multicentre trial. 134 metastatic or recurrent lesions of malignant melanoma in 70 patients were randomly assigned to receive radiotherapy (three fractions of 8 Gy or 9 Gy in 8 days) alone or followed by hyperthermia (43 degrees C for 60 min). Overall, the 2-year actuarial local tumour control was 37 (SE 5)%. Univariate analysis showed a beneficial effect of hyperthermia (radiation alone 28% vs combined treatment 46%, p = 0.008) and radiation dose (24 Gy 25% vs 27 Gy 56%, p = 0.02), but no effect of tumour size (< or = 4 cm 42% vs > 4 cm 29%, p = 0.21). Cox multivariate regression analysis showed the most important prognostic variables to be hyperthermia (odds ratio for 2-year local control 1.73 [95% CI 1.07-2.78], p = 0.023), tumour size (0.91 [0.85-0.99], p = 0.05), and radiation dose (1.17 [1.01-1.36], p = 0.05). Addition of heat did not significantly increase acute or late radiation reactions. Heating was well tolerated, but because of difficulties with equipment only 14% of treatments achieved the protocol objective. The overall 5-year survival rate was 19%, but 38% of the patients for whom all known disease was controlled survived 5 years. Adjuvant hyperthermia significantly improved local tumour control when applied in association with radiation in treatment of malignant melanoma. Successful local treatment of patients with a single or a few metastatic malignant melanoma lesions has significant curative potential.

Adult↗

A randomised open multicentre comparative trial of lamotrigine and carbamazepine as monotherapy in patients with newly diagnosed or recurrent epilepsy.

The efficacy and safety of lamotrigine and carbamazepine as monotherapy in patients with untreated, newly diagnosed or recurrent partial and/or generalised tonic-clonic seizures, were compared in a randomised, open, multicentre study. Patients received 24 weeks' treatment with oral lamotrigine 100 mg (LTG 100, n = 115) or 200 mg (LTG 200, n = 111) or carbamazepine 600 mg (CBZ 600, n = 117). Efficacy measurements were comparable between the three treatment groups, although the higher lamotrigine dose was possibly most effective, with 60.4% completing seizure free compared with 51.3% (LTG 100) and 54.7% (CBZ 600). Both dosage regimens of lamotrigine were well tolerated. More patients on CBZ 600 reported adverse experiences, 66% versus 53% (LTG 100) and 58% (LTG 200), and of these a greater proportion were attributed to CBZ 600 treatment, 53% versus 23% (LTG 100) and 28% (LTG 200). Similarly, a greater proportion of the CBZ 600 group required a change in dose, 47% versus 20% (LTG 100) and 17% (LTG 200) or withdrew completely due to adverse experiences, 10.3% versus 4.3% (LTG 100) and 4.5% (LTG 200). The most common adverse experience leading to withdrawal was rash, with approximately double the proportion of reports occurring in patients on CBZ 600 (5.1%) compared with lamotrigine (1.7% on LTG 100 and 2.7% on LTG 200). Overall lamotrigine appeared equally effective but better tolerated compared with carbamazepine.

Adolescent↗

Synchronous multicentric pleomorphic xanthoastrocytoma: case report.

OBJECTIVE AND IMPORTANCE: Pleomorphic xanthoastrocytoma (PXA) is a rare, low-grade astrocytoma of adolescence. Relatively favorable outcomes have been achieved with complete surgical resection. However, few data exist regarding the treatment of recurrent, deep-seated, or multicentric lesions. We report the first case to our knowledge of synchronous multicentric PXA and discuss the related therapeutic challenges. CLINICAL PRESENTATION: A 13-year-old Hispanic girl presented with a 1-year history of progressive headaches, polyuria, and generalized fatigue. Findings from the neurological examination were notable only for the presence of papilledema. Results of laboratory studies revealed diabetes insipidus and hypothyroidism. The magnetic resonance imaging study revealed numerous nodular, homogeneously enhancing lesions, approximately 1 cm in size, scattered throughout both cerebral hemispheres. INTERVENTION: A right frontal craniotomy was performed for excisional biopsy of a superficial lesion beneath the coronal suture. Results of the histological examination were consistent with a diagnosis of PXA. The patient was treated with whole-brain radiation of 3600 cGy, with additional intensity-modulated boosts to the enhancing lesions of 1440 cGy. Three years after treatment, the patient remains neurologically nonfocal and shows no evidence of disease progression. Surgical intervention will be considered if accessible lesions progress in size on later imaging studies. CONCLUSION: Synchronous multicentric PXA presents unique challenges in that gross total resection would impose significant surgical morbidity; histological homogeneity among the lesions cannot be confirmed; and the well-described potential for anaplastic transformation may be increased with multiple lesions. The optimal treatment for patients with this rare and challenging diagnosis awaits further study.

Adolescent↗

Recurrent cardiac myxoma: why it occurs. A case report with literature review.

Two years after surgical removal of a right atrial myxoma, recurrences were found in both atria: multiple tumors in the right atrium and one tumor in the left atrium. All were subsequently removed. There was no further recurrence during the following 3 years. We report on an unusual case which, to our knowledge, is the first time that such a case appears in the literature. We also discuss the clinical symptoms, diagnostic aspects, as well as details of a literature review regarding recurring myxoma. We think the recurrence in our case was due to totipotent multicentricity of the tumor. Previous studies showed that the recurrence might be due to the following reasons: inadequate resection, or multifocal pattern behaviour of a benign myxoma, either in the same or in a different location as the primary tumor. Familial disposition may also play a role in recurrent development. The abnormal DNA ploidy pattern of myxoma patients showed a high recurrence.

Adolescent↗

[Four cases of upper urinary tract transitional cell carcinoma after radical cystectomy in bladder cancer].

One hundred and eighty-six patients with primary transitional cell carcinoma underwent radical cystectomy between 1965 to December, 1986. Four of them (2.2%) had developed upper urinary tract transitional cell carcinoma. Three of the 4 patients had received various transurethral treatments for the primary bladder lesions before radical cystectomy, but one patient had undergone total cystectomy and ileal conduit as primary treatment. All of the upper urinary tract tumors were invasive. Three patients died and one is alive. We consider the following to be high risk patients for the development of upper tract recurrence. 1) patients with carcinoma-in-situ and multicentric tumors in the bladder, 2) patients with recurrent bladder cancer treated with bladder preserving treatment for a long periods, 3) patients with vesicoureteral reflux, and 4) occupational bladder cancer patients.

Aged↗

Frequency and risk factors of recurrent pain during refeeding in patients with acute pancreatitis: a multivariate multicentre prospective study of 116 patients.

BACKGROUND/AIMS: The period of refeeding in patients with acute pancreatitis is critical because they may have pain relapse. A multicentre, multidimensional, prospective study was performed to assess the frequency and the risk factors of pain relapse in these patients. METHODS: Patients were included if they had acute pancreatitis severe enough to stop oral feeding for more than 48 hours. Clinical, biochemical, radiological, and therapeutic data were prospectively recorded and analysed by unidimensional and multidimensional analysis. The moment to refeed patients was chosen by the clinician but the diet was the same in all centres. RESULTS: A total of 116 patients were included with a Ranson's bioclinical score > or = 3 in 35% and a Balthazar's CT score > or = D in 42%. The cause of acute pancreatitis was biliary in 47% and alcohol misuse in 31%. During the oral refeeding period, 21% of the patients had pain relapse. This occurred on days 1 and 2 in 50% of patients. The duration of the painful period was longer in patients who relapsed than in others (p < 0.002). Pain relapse occurred in 39% of patients with a serum lipase concentration > 3x the upper limit of the normal range the day before refeeding and in 16% of other patients (p < 0.03). Patients with higher Balthazar's CT scores had pain relapse more often than the others (p < 0.002). None of the therapeutic procedures significantly modified the frequency of pain relapse. Using multidimensional analysis, Balathazar's CT score, period of pain, and serum lipase concentration the day before refeeding were independently associated with an increased risk of pain relapse. At a threshold of 0.5, a logistic score had a 37% sensitivity, 95% specificity, and 83% accuracy to predict pain relapse. Pain relapse nearly doubled total hospital stay and hospital stay after the first attempt at oral refeeding. CONCLUSION: Pain relapse occurred in one fifth of the patients with acute pancreatitis during oral refeeding and was more common in patients with necrotic pancreatitis and with longer periods of pain. The results of this study can be used to predict high risk patients and are a first step in the prevention of pain relapse.

Acute Disease↗

Early application of an implantable loop recorder allows effective specific therapy in patients with recurrent suspected neurally mediated syncope.

AIMS: This prospective multicentre observational study assessed the efficacy of specific therapy based on implantable loop recorder (ILR) diagnostic observations in patients with recurrent suspected neurally mediated syncope (NMS). METHODS AND RESULTS: Patients with three or more clinically severe syncopal episodes in the last 2 years without significant electrocardiographic and cardiac abnormalities were included. Orthostatic hypotension and carotid sinus syncope were excluded. After ILR implantation, patients were followed until the first documented syncope (Phase I). The ILR documentation of this episode determined the subsequent therapy and commenced Phase II follow-up. Among 392 patients, the 1-year recurrence rate of syncope during Phase I was 33%. One hundred and three patients had a documented episode and entered Phase II: 53 patients received specific therapy [47 a pacemaker because of asystole of a median 11.5 s duration and six anti-tachyarrhythmia therapy (catheter ablation: four, implantable defibrillator: one, anti-arrhythmic drug: one)] and the remaining 50 patients did not receive specific therapy. The 1-year recurrence rate in 53 patients assigned to a specific therapy was 10% (burden 0.07 +/- 0.2 episodes per patient/year) compared with 41% (burden 0.83 +/- 1.57 episodes per patient/year) in the patients without specific therapy (80% relative risk reduction for patients, P = 0.002, and 92% for burden, P = 0.002). The 1-year recurrence rate in patients with pacemakers was 5% (burden 0.05 +/- 0.15 episodes per patient/year). Severe trauma secondary to syncope relapse occurred in 2% and mild trauma in 4% of the patients. CONCLUSION: A strategy based on early diagnostic ILR application, with therapy delayed until documentation of syncope allows a safe, specific, and effective therapy in patients with NMS.

Adult↗

Early detection of breast cancer recurrences through periodic follow-up--is it useless?

The authors report on a multicentric consecutive series of 1120 breast cancer first recurrences. Cases detected as subjectively asymptomatic thanks to periodic follow-up examinations are compared to cases detected as symptomatic. The relapse-free interval from primary treatment was shorter for asymptomatic recurrences, confirming that an earlier diagnosis was achieved in these cases. In spite of this diagnostic anticipation, median and actuarial survival from primary treatment did not differ when asymptomatic recurrences were compared to symptomatic recurrences. The study results did not show any prognostic impact of periodic follow-up in breast cancer and urge for prospective controlled studies on this diffuse and expensive practice.

Breast Neoplasms↗

DNA cytometric features in biopsies of TaT1 urothelial cell cancer predict recurrence and stage progression more accurately than stage, grade, or treatment modality.

OBJECTIVES: To compare retrospectively the predictive value for recurrence and stage progression of DNA ploidy and S-phase fraction by flow cytometry and highly automated ultrafast image cytometry (ICM) in biopsies of TaT1 urothelial cell carcinomas (UCCs) of the urinary bladder with stage, grade, other pathologic features, and treatment. METHODS: Three experienced pathologists reviewed the stage and grade of 228 UCCs; 193 (85%) consensus cases were analyzed further. We had enough material for single-cell suspensions for both flow cytometry and ICM in 183 cases (94.8%). The 2001 European Society for Analytical Cellular Pathology standards for DNA ICM were followed. The predictive value of DNA features, classic prognosticators (stage, grade, carcinoma in situ, multicentricity), and treatment modality for recurrence and stage progression were analyzed with univariate (Kaplan-Meier) survival and multivariate (Cox model) regression analysis. Ta and T1 cases were analyzed separately. RESULTS: Of the 228 cases, 88 (51.5%) recurred and 13 (7.6%) progressed. On univariate analysis, most of the DNA features studied were statistically significant. Treatment modality and grade were only prognostic for progression (not for recurrence) and only in Ta cases. On multivariate analysis, DNA ICM features performed best; the strongest recurrence predictor for Ta UCC was a DNA index (DI) of 1.0 versus all others, and for T1 UCC, a DI of less than 1.3 versus 1.3 or greater. The best stage progression predictor for Ta UCCs was a DI of 1.0 plus an S-phase fraction of less than 10%, and for T1 UCCs, a DI of less than 1.3 versus 1.3 or greater. With multivariate analysis, sex, age, grade, carcinoma in situ, multicentricity, and treatment modality were excluded once the DNA ICM features were selected. CONCLUSIONS: DNA image cytometric features predict recurrence and stage progression in TaT1 UCC biopsies more accurately than classic prognostic factors, independent of treatment modality.

Aged↗

Multicentric study comparing intravesical chemotherapy alone and with local microwave hyperthermia for prophylaxis of recurrence of superficial transitional cell carcinoma.

PURPOSE: To compare the efficacy and local toxicity of the intravesical instillation of a cytostatic drug versus the same cytostatic agent in combination with local hyperthermia as an adjuvant treatment, after complete transurethral resection (TURB) of superficial transitional cell carcinoma (TCC) of the bladder. PATIENTS AND METHODS: The study was designed as a prospective, multicentric, randomized trial. Eighty-three patients suffering from primary or recurrent superficial (Ta-T1) TCC of the bladder, after a complete TURB, were randomly assigned to receive intravesical instillations of mitomycin C (MMC) alone, for 41 patients, and MMC in combination with local microwave-induced hyperthermia, for 42 patients. For the combined approach, a new system, Synergo101-1 (Medical Enterprises, Amsterdam, the Netherlands) was used. The effectiveness evaluation end points of the study were evaluation of recurrence-free survival and the estimated probability of recurrence. The safety evaluation end points included subjective and objective side effects and clinical complications. For the efficacy end point, Kaplan-Meier analysis was employed, with the log-rank test for significance. Minimum follow-up time was 24 months. RESULTS: Of the 83 randomly assigned patients, 75 completed the study according to the protocol and had valid cystoscopy results. Survival analysis of the 75 assessable patients demonstrated a highly significant difference in the survival curves in favor of thermochemotherapy. Subjective intolerance and clinical complications were significantly higher but transient and moderate in the combined treatment group. CONCLUSION: In our series, endovesical thermochemotherapy appears to be more effective than standard endovesical chemotherapy as an adjuvant treatment for superficial bladder tumors at 24-month follow-up, despite an increased but acceptable local toxicity.

Administration, Intravesical↗

Pathologic features related to local recurrence following lumpectomy and irradiation.

Breast conservation (lumpectomy and irradiation) has grown increasingly popular as a primary therapy for breast cancer. For the majority of patients whose breast cancers are now being detected at T1N0, both the expected cosmetic result and the survival are excellent. For this reason the possibility of local recurrences in the breast has a disproportionally larger impact on treatment planning for these patients. Although the majority of local recurrences occur in the vicinity of the primary tumor site within the initial 5 years of irradiation, local recurrences can be expected to occur well into the second decade as follow-up is continued. The majority of these late recurrences will not be in the immediate vicinity of the prior excision but represent de novo breast cancers developing in a multicentric fashion in other quadrants. Factors which influence recurrence per se include the size, grade, and stage (nodal status) of the tumor. Such factors influence local, locoregional, and distant metastases. A number of pathologic factors appear to affect only local recurrences. These, including positive margins, gross multicentricity, extensive intraductal carcinoma, and invasive lobular carcinoma, all share a common feature of a greater likelihood of local residual tumor burden. The increased risk of local recurrences related to positive surgical margins and extensive intraductal carcinoma can largely be eliminated by increasing the volume of tissue excised or the radiation dose. In summary, there are no absolute contraindications based on pathologic features of the tumor or the state of the resection margins which should preclude consideration of breast conservation for an individual patient.

Breast Neoplasms↗

Percutaneous ethanol injection therapy for recurrent hepatocellular carcinoma.

Recently, small hepatocellular carcinoma (HCC) has been detected by following up patients with chronic liver diseases using ultrasonography (US). Most of the HCC patients have liver cirrhosis, and multinodular lesions are often found, even in cases of small HCC. Thus, surgical resection for small HCC is of limited efficacy. Our follow-up study indicated that a recurrent lesion was observed in 96.1% of small HCC cases after successful percutaneous ethanol injection therapy (PEIT). It is therefore very important to follow-up patients initially treated with PEIT with US for the detection of newly developed tumor nodules, because of the multicentric nature of HCC. A recurrence is subsequently again treated with PEIT. The 5-year survival rate of our 250 small HCC cases treated by PEIT is 46.7%. However, cases not followed by regular US after the first PEIT show significantly poorer 5-year survival rates. In future, it would appear to be of importance to search for means to inhibit or prevent recurrence.

Carcinoma, Hepatocellular↗

DNA ploidy pattern in synchronous and metachronous hepatocellular carcinomas.

DNA ploidy of hepatocellular carcinoma (HCC) was studied in 28 patients using a flow cytometric method. Fourteen patients had two HCCs synchronously, and the remaining 14 had tumor recurrence in the remnant liver 3-41 months after curative resection of primary HCCs. DNA ploidy pattern and histopathologic parameters were compared between the synchronous and metachronous HCCs. Among those with synchronous HCCs, both tumors were diploid in 7 cases and aneuploid in 2 instances. Five patients had HCCs of different DNA ploidy pattern. On the other hand, 5 of 14 patients with metachronous HCCs had a consistent DNA ploidy between primary and recurrent tumors. In 4 cases, the first tumor was diploid whereas the recurrent HCC was aneuploid or tetraploid. In the remaining 5 cases, the primary HCC was aneuploid, but the recurrent tumor was diploid. Assuming that the difference in DNA ploidy pattern indicates a different clonal origin, the current results indicate that at least 36% of synchronous HCCs and 64% of recurrent HCCs develop in a multicentric fashion.

Adult↗

Topical treatment of recurrent genital herpes simplex virus infections with trisodium phosphonoformate (foscarnet): double blind, placebo controlled, multicentre study.

A double blind, placebo controlled trial was performed in nine sexually transmitted diseases (STD) clinics in the United Kingdom and the Netherlands to investigate the efficacy of trisodium phosphonoformate (foscarnet) cream in treating recurrent genital herpes simplex virus (HSV) infection. The study group comprised 145 male and 85 female patients. Men received 0.3% foscarnet cream and women 1% foscarnet cream for five days. The difference in time to healing between patients receiving foscarnet or placebo was not significant. Fewer patients treated with foscarnet had positive viral cultures after treatment, but the difference was not significant. The development of new lesions, however, was significantly less common in patients given foscarnet. Though topical foscarnet is a safe drug, no appreciable efficacy in treating recurrent genital HSV infection could be shown.

Administration, Topical↗

Recurrent solitary reticulohistiocytoma of the eyelid.

A healthy 13-year-old female presented with a 5-month history of an enlarging red-brown, firm lower eyelid mass associated with loss of eyelashes. An excisional biopsy revealed a well-circumscribed nodule composed of coalescing nests of epithelioid cells, rare multinucleated cells, and vacuolated macrophages and spindle cells. Additional studies revealed a positive vimentin and alpha(1)-antitrypsin, and negative S100 protein and Factor XIIIa immunophenotype. This constellation of clinicopathologic features is diagnostic of solitary reticulohistiocytoma, but also shows overlap with xanthogranuloma, a common childhood histiocytosis. Reticulohistiocytoma should be considered in the differential diagnosis of eyelid tumors and has the potential for local recurrence. Diffuse cutaneous reticulohistiocytosis or multicentric reticulohistiocytosis should be considered if similar cutaneous lesions with or without symptoms of arthritis are present, respectively.

Adolescent↗