ARFI-based tissue elasticity quantification in comparison to histology for the diagnosis of renal transplant fibrosis.

BACKGROUND AND PURPOSE: Until recently clinical diagnosis of chronic renal allograft dysfunction could only be established invasively by renal biopsy. Given the risks of that procedure, a non-invasive, diagnostic test would be very advantageous. Novel ultrasound-based elasticity tools, using "Acoustic Radiation Force Impulse (ARFI)" technology are now available. Previously this technique has been utilised to quantify liver fibrosis. First results of these studies are promising. The purpose of our study was to investigate correlation between stiffness values obtained by ARFI-quantification and histological fibrosis score in renal transplants. METHODS: We employed "Virtual Touch™ tissue quantification" (Siemens Acuson, S2000) to quantitatively measure tissue stiffness in the cortex of transplant kidneys. Eighteen patients were included in this prospective study, recording close temporal ARFI-quantification and fibrosis measurements. All patients undergoing renal transplant biopsy were examined with ARFI-quantification (15 measurements per transplant kidney). Resistive indices were also calculated from pulsed-wave Doppler ultrasound. Transplant biopsies were histologically evaluated by a reference nephropathologist and graded according to the percentage of fibrosis and to the BANFF-score. Due to the non-normal distribution of the data the Spearman-correlation-coefficient (rho) was used to assess the bivariate relationship of ARFI and fibrosis in the transplant kidney. RESULTS: There was a significant positive moderate correlation between mean ARFI-values and the grade of fibrosis (rho = +0.465; p = 0.026). This correlation was also valid for the mean ARFI-values and the BANFF-category (rho = +0.468; p = 0.025). There was no significant correlation between the mean ARFI-values and the resistive indices in the transplant kidney (rho = +0.034; p = 0.904). Nevertheless, a positive correlation between the mean RI-values of the kidney and the grade of fibrosis was established (rho = +0.563; p = 0.015). CONCLUSION: The mean values of ARFI measurements and the resistive indices are potentially independent explanation variables for evaluating the grade of fibrosis in transplant kidneys.

[13-cis retinoic acid and interferon-alfa-2a as palliative therapy in pretreated, recurrent squamous epithelial carcinoma of the cervix uteri and vulva]. / 13-cis Retinolsäure und Interferon alpha 2 a als Palliativtherapie beim vorbehandelten, rezidivieren-den Plattenepithelkarzinom der Zervix uteri und Vulva.

Patients with metastasising carcinoma of the uterine cervix or recurrent disease, in whom local treatment as surgery or radiotherapy has failed, are still an unsolved problem. Platinum-based multi-agent chemotherapies achieve overall response rates up to 60%, but side effects are serious and so far no survival benefit has been proven. Recent publications report on a synergistic effect of combination therapy using 13-cis-retinoic acid and interferon alpha-2 a in the treatment of squamous cell carcinoma of the cervix. In a pilot study we include 6 patients with locally recurrent or metastasising squamous cell carcinomas, five of the uterine cervix, one of the vulva. The systemic therapy consisted of-orally administered 13-cis-retinoic acid (80 mg q. d.) and subcutaneously injected interferon alpha-2 a (6 x 10(6) I.E. q. d.). All patients were primarily treated by surgical and/or radiation therapy. In each case chemotherapy had been either already performed or rejected by the patient. Median duration of treatment was 52 days, median survival time 107 days. Out of 6 patients 3 experienced progression of disease uninfluenced by therapy. One patient with multiple subcutaneous lymph node metastases showed mixed response for a short period of 3 weeks before progression and eventual death. One patient had no change or disease for 13 months with subsequent progression and eventual death after 22 months. One patient could not be evaluated for an allergic reaction after only 15 days of treatment. Other side effects were "flu-like symptoms", skin irritations, conjunctivitis sicca and chileitis, all WHO 1-2. Overall toxicity must be rated low compared to standard chemotherapy, but is not negligible. In our study the positive reports in literature concerning the treatment of primary advanced cervical cancer and recurrent advanced carcinoma of the skin could not be reproduced. This might be due to the small number of cases, which is a common problem in immunotherapeutic studies. Moreover, very unfavourable patient selection criteria in our study compared to primarily untreated patients may also have contributed to different response rates. However, in our opinion the tested regimen cannot be considered sufficiently effective in patients suffering from pretreated, recurrent squamous cell carcinoma of the cervix or vulva.

[Value of tumor-reductive secondary operation (interventional laparotomy) in ovarian cancer]. / Stellenwert der tumorreduktiven Sekundäroperation (Interventionslaparotomie) beim Ovarialkarzinom.

Only 20-50% of patients with advanced ovarian cancer have minimal residual disease after aggressive primary cytoreductive surgery. For patients with residual tumour, responding to platinum-based chemotherapy, new therapeutic procedures should be attempted. In most cases, the benefit of performing secondary surgery could not be clearly demonstrated. But there is a consensus of opinion that a second-look procedure in order to confirm complete remission does not improve survival. Between January 1984 and July 1990, 346 patients with primary ovarian cancer were treated at our institution. 190 patients underwent secondary surgery, 93 of these had secondary debulking and are part of the study. After secondary cytoreductive surgery 38 patients (41%) had no residual disease, 35 patients (38%) had disease less than 2 cm, and 20 patients (21%) had disease greater than 2 cm. Mean survival in patients with no residual disease after secondary debulking surgery was 46 months and significantly longer as in patients with residual disease. Patients with residual tumour at primary surgery and no secondary cytoreductive operation survived 35 months, with a significant difference to the patients with secondary debulking and no residual disease. Secondary debulking surgery should be performed in all patients in whom minimal residual disease can be achieved. Preoperative diagnostic tools, including CA 125 value, computed tomography and immunoscintigraphy, should predict a tumour-free situation after secondary cytoreductive surgery.

[The value of reoperation in the treatment of ovarian cancer]. / Stellenwert der Rezidivchirurgie in der Behandlung des Ovarialkarzinoms.

Recurrent ovarian cancer is still a significant problem despite intensive primary therapy, consisting of radical surgery and subsequent chemotherapy. The primary reason for consequent follow up investigations and immediate start of second-line therapy in cases of recurrence is based on the fact, that patients with relapse more than 12 months after primary therapy have a mean survival of 105 weeks after diagnosis. The value of surgical treatment is controversially discussed in the literature. Several authors argue, that there is no definitive prolongation of survival. Between January 1984 and July 1990, 285 patients presented themselves at our hospital with recurrence or progression of ovarian cancer. 72 of these patients had surgical treatment and those patients are part of the investigation. The mean survival of the patients (n = 18), which were operated with no remaining tumour, was 166 weeks. The average survival time of the 22 women with up to 2 cm remaining tumour was 108 weeks. The average survival time of the 32 patients with more than 2 cm after surgery was 72 weeks. One important criterion for the achievable tumour-free situation after surgery was the distinction between primary progression and relapse, where relapse was defined as recurrence more than 12 months after primary treatment. 29% of the patients with relapse could be operated tumour-free, a situation which could be achieved only in one of 13 patients (8%) with primary progression of the disease. Surgery in recurrent ovarian cancer is only indicated in patients with relapse more than 12 months after primary surgery. Tumour-free patients have significant benefit from the surgical procedure.(ABSTRACT TRUNCATED AT 250 WORDS)