HER-2/neu (c-erbB-2) evaluation in primary breast carcinoma by fluorescent in situ hybridization and immunohistochemistry with special focus on intratumor heterogeneity and comparison of invasive and in situ components.

We have studied the intratumor HER-2/neu heterogeneity in 78 consecutive and population-based primary invasive breast carcinomas. Within the invasive component, heterogeneity was detected in only 1 of 78 tumors. In 48 tumors (62%), we found both in situ and invasive components in analyzed tissue sections. Twelve of these 48 tumors had a difference of at least 2 arbitrary units in the in situ compared with the invasive part of the tumor with regard to the HER-2/neu status analyzed by HercepTest (immunohistochemistry). Eight of these 12 tumors were reanalyzed with fluorescent in situ hybridization and immunohistochemistry with and without a new Automated Cellular Imaging System. In this limited material, immunohistochemistry in combination with the Automated Cellular Imaging System seemed to have a better correlation with fluorescent in situ hybridization than immunostaining analyzed manually. In conclusion, HER-2/neu expression is not seldom heterogeneous in invasive compared with in situ components within a tumor. This finding should be considered in the choice of evaluation method. To avoid heterogeneity as a confounding factor in HER-2/neu analyses, detection methods such as immunohistochemistry and fluorescent in situ hybridization, which can provide evaluation in a preserved tissue architecture, should be used. Perhaps the intratumor HER-2/neu heterogeneity can explain some of the unexpected failures of trastuzumab therapy.     

Long-term results of simple and radical nephrectomy for renal cell carcinoma

From 1974 to 1983, simple and radical nephrectomies were performed at the Chaim Sheba Medical Center (Tel Hashomer, Israel) for renal cell carcinoma. The authors reviewed 109 cases that were followed for a period ranging from 5 to 14 years. Simple nephrectomy was performed in 55 patients, and 54 patients underwent radical nephrectomy. The selection of the surgical procedure was based on the surgeon's preference and not on the basis of clinical stage, age, or sex. The surgical results and survival rates were assessed according to the pathologic stage of the tumors. Among patients with Stage I tumor, radical nephrectomy produced better survival rates at 5 and 10 years (P = 0.03); however, when the non-cancer deaths were excluded, the difference in survival was not statistically significant. For Stage I tumors the survival free of disease at 5 years was better for the radical nephrectomy group, but this difference was not statistically significant. No difference was noticed in the local recurrence rate between the two groups. Nephrectomy in patients with Stage IV disease did not alter survival regardless of the type of operation.     

Cisplatin-5-fluorouracil chemotherapy for advanced inoperable squamous carcinoma of the head and neck

Patients with locally advanced, inoperable squamous cell carcinoma of the head and neck were offered three courses of cisplatin and 96-h 5-fluorouracil (5-FU) infusion. Subsequent therapy included surgery when feasible, irradiation therapy, and a maintenance program of methotrexate (MTX)-5-FU. Thirty-three patients were evaluated prospectively. Seven patients underwent a single course of chemotherapy. Five patients underwent two courses of chemotherapy. Twenty-one patients underwent three courses of adjuvant chemotherapy. The overall response rate was 48% (16 of 33). Fifteen of 21 patients (76%) receiving three courses of chemotherapy evidenced a response; this included three complete responses (CRs) (9%). No responses were seen in patients receiving only one or two courses of chemotherapy. Among responding patients, the initial favorable response to chemotherapy was apparent after the first course of chemotherapy. Patients who failed to demonstrate any response after two courses of chemotherapy did not respond after a third course. A significant group of patients fail to respond and should be offered participation in other investigational protocols as they become available.     

Die Aufklärungspflicht bei endoskopischen Operationen

Ohne Zusammenfassung     

Gonadotrophin-releasing hormone agonist therapy for hirsutism is as effective as high dose cyproterone acetate but results in a longer remission

Both cyproterone acetate (CPA) and the gonadotrophin-releasing hormone agonist (GnRHa) have been shown to be effective for the treatment of hirsutism. We wished to compare the effectiveness of CPA in two standard doses with GnRHa and add-back therapy and to compare the length of remission after these treatments. A total of 60 hirsute hyperandrogenic women was assigned to the following treatment groups: CPA 2 mg with 35 microg of ethinylestradiol for 21 days each month (Diane group), CPA 50 mg, days 5-15, and ethinylestradiol 50 microg, days 5-25, each month (CPA group) or Decapeptyl 3.75 mg i.m. every 28 days with the addition of conjugated oestrogen 0.625 mg, days 1-21, and medroxyprogesterone acetate 10 mg, days 12-21 (GnRHa group). Hirsutism was graded by the Ferriman-Gallwey-Lorenzo (FGL) index and anagen hair shaft diameters and serum luteinizing hormone (LH) and testosterone were assessed before and every 3 months during and after treatment. All women were treated for 1 year with 1 year follow-up. At baseline hirsutism and endocrine patterns were similar in all groups. After one year of treatment, hirsutism decreased in all groups but the changes were greater (P <0.05) in the CPA and GnRHa groups than in the Diane group. Serum LH and testosterone were lowest in the GnRHa group. After withdrawal, hirsutism increased rapidly in the Diane and CPA groups and after 6 months, FGL scores and hair shaft diameters were similar to pretreatment values. In the GnRHa group, hirsutism increased more gradually and after 1 year of withdrawal, FGL scores and hair diameters were significantly (P <0.05) less than pretreatment values. Serum LH and testosterone increased rapidly in all three groups reaching pretreatment values by 6 months. These data suggest equal efficacy of the GnRHa and the high dose CPA regimen for the treatment of hirsutism in hyperandrogenic women. GnRHa with add-back treatment appears to result in a longer remission of hirsutism in comparison with CPA.      

Histological and scanning electron microscopic alterations in ileal conduit depending on the time factor

Five ileal conduit biopsies, taken after 1-7 years, were examined by light microscopy and scanning electron microscopy. The total height of the lamina mucosa decreased from 700 to 275 microns. The height of the villi diminished from 550 to 50 microns; the depth of the crypts increased from 130 to 244 microns and the villus-crypt index changed from 4.2 to 0.2. Signs of chronic inflammation could be observed. Scanning electron microscopy shows that the number of microvilli per cell was markedly reduced. There was a varied picture of different stages of atrophy. After 3 years microvilli could no longer be observed. In view of the prolonged urinary contamination time, it appears to be imperative to check neobladders with regard to possible carcinoma induction.     

Maxillary sinusitis in adults: an evaluation of placebo-controlled double-blind trials

BACKGROUND: In general practice, acute sinusitis is frequently diagnosed and treated with antibiotics. OBJECTIVE: This study aimed to determine the evidence for the effectiveness of antibiotic treatment in acute maxillary sinusitis in adults by assessing the methodological quality of placebo-controlled double-blind randomized trials. METHOD: An evaluation by four raters through a 35-item scoring-scale for internal and external validity of all placebo-controlled double-blind randomized trials on acute sinusitis found between January 1966 and July 1996. RESULTS: Eighty-five trials were excluded because they were not placebo-controlled, double-blind, randomized, or were carried out in patients with chronic sinusitis or in children. The three remaining trials were performed in different populations (one in general practice) between 1973 and 1978. Only one study claimed superiority of antibiotic treatment. Different inclusion criteria and major outcome measures were used by the authors. The reliability of major outcome events was reported poorly or not at all and in two studies outcome measures were clinically inappropriate. The studies scored 30-62% of the maximum attainable score for internal validity and 10-20% for external validity. CONCLUSION: The effectiveness of antibiotic treatment in acute maxillary sinusitis in a general practice population is not based sufficiently on evidence.      

Parapapillary diameter of retinal vessels. I. Estimating the size of the optic papilla (a papillometric study of over 264 normal eyes)

The diameter of the temporal superior and inferior retinal artery and vein were measured at the optic disk border and 2 mm from the disk center in 264 nonselected normal eyes on the basis of photographs, with correction of magnification. Additionally, the individual ocular magnification factor was determined by Littmann's method. The mean caliber of the artery was 0.113 +/- 0.019 mm at the disk border and 0.118 +/- 0.023 2 mm from the disk center. The corresponding values for the vein were 0.149 +/- 0.026 mm and 0.159 +/- 0.026 mm. The correlations between vessel caliber and disk size were not significant, but the relationship between disk size and the quotient of vessel diameter divided by disk size was highly significant (p less than 0.0001). Vessel diameter can therefore be taken as an independent unit for determining optic disk size in relative and approximately also in absolute units. Thus, mean horizontal disk diameter (1.77 +/- 0.33 mm) corresponded to 16.3 +/- 3.5 artery and 12.3 +/- 2.6 vein diameters (measured at the optic disk border). The mean individual ocular magnification factor was 0.302 +/- 0.017, with a Gauss standard distribution. If the optical characteristics of a photographed eye are not known and the ocular magnification factor is assumed to be 0.302, then 68.3% of all eyes will be covered with an inaccuracy of 5.6% and 95.5% of all eyes with an inaccuracy of 11.2%.