High-dose chemotherapy with autologous hematopoietic stem-cell support compared with standard-dose chemotherapy in breast cancer patients with 10 or more positive lymph nodes: first results of a randomized trial.

PURPOSE: Investigation of high-dose chemotherapy (HD-CT) followed by autologous hematopoietic stem-cell support compared with standard-dose chemotherapy (SD-CT) as adjuvant treatment in patients with primary breast cancer and 10 or more positive axillary lymph nodes. PATIENTS AND METHODS: Between November 1993 and September 2000, 307 patients were randomized to receive (following four cycles of epirubicin 90 mg/m(2) and cyclophosphamide 600 mg/m(2), intravenously every 21 days) either HD-CT of cyclophosphamide 1500 mg/m(2), thiotepa 150 mg/m(2), and mitoxantrone 10 mg/m(2), intravenously for 4 consecutive days followed by stem-cell support; or SD-CT in three cycles of cyclophosphamide 500 mg/m(2), methotrexate 40 mg/m(2), and fluorouracil 600 mg/m(2) intravenously on days 1 and 8, every 28 days. The primary end point was event-free survival. RESULTS: After a median follow-up of 3.8 years, 144 events with respect to event-free survival have been observed (HD-CT: 63 events; SD-CT: 81 events). The first event of failure (HD-CT v SD-CT) was an isolated locoregional recurrence (nine v 11), a distant failure (52 v 68), and death without recurrence (two v two). The estimated relative risk of HD-CT versus SD-CT was 0.75 (95% CI, 0.54 to 1.06; P =.095). Overall survival showed no difference (HD-CT: 40 deaths; SD-CT: 49 deaths). CONCLUSION: There was a trend in favor of HD-CT with respect to event-free survival, but without statistical significance. Further follow-up and a meta-analysis of all randomized studies will reveal the effect of HD-CT as compared with SD-CT as adjuvant treatment in high-risk primary breast cancer.

Comparison of classic and endoscopic lymphadenectomy for staging breast cancer.

STUDY OBJECTIVE: To compare endoscopic and classic axillary lymphadenectomy staging of breast cancer with respect to operation-induced changes such as seroma formation, pain, neurologic sensations, lymphedema, infection, and reduction of shoulder-arm mobility. DESIGN: Prospective, randomized study (Canadian Task Force classification I). SETTING: University-affiliated hospital. PATIENTS: Eighty consecutive women with histopathologically confirmed invasive breast cancer who had clinically and sonographically negative axillary lymph nodes (<1 cm). INTERVENTION: Classic and endoscopic lymphadenectomies. MEASUREMENTS AND MAIN RESULTS: We attempted to obtain 10 axillary lymph nodes/patient. After 1, 3, 5, 7, 9, 42, and 84 days, clinical and ultrasonographic examinations were conducted to evaluate operation-induced changes. Short-term results showed that, with endoscopic technique, a representative number of axillary lymph nodes was removed, with reduced axillary infiltration and seroma induction, as well as less impaired shoulder-arm mobility. During the first month, postoperative infection, lymphedema, and neurologic complaints were comparable in both groups, with more stretching pain in the classic group and predominantly paresthesia in the endoscopic group. After 3 months no differences in postoperative complications were detected. CONCLUSIONS: Endoscopic axillary lymphadenectomy avoids short-term reduction of shoulder-arm mobility. Long-term studies are necessary to prove if this technique is as safe as the classic procedure with regard to local axillary recurrence. If so, endoscopy could become the method of choice for staging breast cancer in women with clinically negative lymph nodes.

The uterotubal junction. A proposal for classifying its morphology as assessed with hysteroscopy.

Hysteroscopy was used to characterize the morphology of the uterotubal ostium (UTO). A comparison was made with the laparoscopic assessment of the tube in 86 infertile women. In addition, histology was performed on the UTO from women undergoing hysterectomy for cervical dysplasia. These comparisons revealed that the incidence of mucosal damage to the UTO is not related to that of adnexal adhesions unless the postinflammatory changes are severe. Most notable was the correlation between endosalpingeal hyperplasia and salpingitis isthmica nodosa.

Therapeutic laparoscopy. An update on the instrumentation.

The ancillary instruments in therapeutic laparoscopy can be divided into passive ones, which stabilize or manipulate, and active ones, which "treat" the tissue. Eight new instruments have been developed. In the passive category are oviduct, mesoovary, adhesion and pin forceps. In the active category are a dividing spatula, bipolar microforceps, self-tying suture and swab carrier. This diversification of instrumentation ensued from the restricted number of instruments that may be used simultaneously at laparoscopy, and the new designs help reduce the duration of laparoscopic operations.

Standardizing microcolposcopy. Assessing the criteria for evaluating the presence and degree of cervical intraepithelial neoplasia.

We established criteria for the detection and grading of cervical intraepithelial neoplasia with microcolposcopy. These criteria were assessed for their accuracy through comparison with the histologic evaluation of cone biopsy or hysterectomy specimens in 26 highly selected cases. There was a positive correlation of 88.5% and no false-negative cases. Microcolposcopy, performed in a standardized manner, may be a valuable adjuvant to colposcopy.

Effects of castration, exogenous testosterone and estrogen on endotoxin response in male rats.

Using an experimental model of continuous endotoxin infusion, the effects of castration, testosterone and estrogen substitution on disseminated intravascular coagulation in male rats were investigated. Male rats which are not pretreated react in the same way to an endotoxin infusion as female animals, with an increase in free plasma hemoglobin, decrease of fibrinogen level, decrease of hematocrit and platelets and glomerular fibrin depositions. Different experimental groups of testectomized rats were pretreated with (i) 0.3 micrograms (pregnancy-conserving dose) or (ii) 30 micrograms ethinylestradiol (ovulation-suppression dose) or (iii) 250 mg testosterone. They were then compared to groups of animals treated with sesame oil as well as untreated group of rats. The pretreatment with testosterone and estrogens in the small-dose group had only an insignificant effect on the shock sequence. Only those animals which were treated with a high dose of estrogens showed a dramatic enhancement of their endotoxin sensitivity. It was also shown that in male animals an increased estrogen level might mediate a state of 'preparation', but testosterone does not 'prepare' castrated rats for the generalized Schwartzman reaction. The possible significance of enhancement of endotoxin toxicity by estrogens in explaining some pathophysiological characteristics of disseminated intravascular coagulation in pregnancy is discussed.

Recovery of ovarian function after laparoscopic treatment of acute adnexal torsion. A case report.

Adnexal torsion due to an ovarian cyst was treated laparoscopically by fenestration of the cyst and shortening of the ovarian ligament. Serial ultrasound examinations three months later demonstrated recovery of follicular growth.

[Effect of uterotonic agents on the pathophysiology of endotoxin-induced shock]. / Der Einfluss von Uterotonika auf die Pathophysiologie des endotoxin-induzierten Schocks.

Different uterus contracting compounds (methylergonovine, oxytocin and prostaglandin F2 alpha) were evaluated with respect to their effect on the pathophysiology of endotoxin-induced shock. We used the model developed by Beller and Theiss of a continuous endotoxin-infusion in female Sprague-Dawley rats. In each group fibrinogen, plasma hemoglobin, hematocrit and thrombocytes were measured. The body weight of the rats was determined before and after the infusions. After the end of the experiment the intravasal fibrin deposits in the kidneys were evaluated quantitatively. Methylergonovine showed a slight protective effect regarding the clotting system and the shock events. This effect was more pronounced with oxytocin. In contrast prostaglandin F2 alpha enhanced the shock events. Based on our results we feel that the use of prostaglandin F2 alpha under septic conditions can be associated with significant risks.

[Changes in prostaglandins in endotoxin-induced shock in pregnant minipigs]. / Prostaglandinveränderungen während des Endotoxin-induzierten Schocks bei schwangeren Minischweinen.

Six pregnant mini-pigs received a continuous endotoxin infusion of 1 mg/kg body weight. E.-coli-lipopolysaccharide, two control animals were treated in the same way without endotoxin application. Blood was drawn from the fetal umbilical cord after exposure through a uterine window. In contrast to the controls, concentrations of prostaglandin F2 alpha increased in animals which received endotoxin infusions. The prostaglandin-E2-concentrations in the treated pregnant animals decreased by half during the first hour of the experiment, whereas they staid fairly constant in the untreated group of animals. The thromboxane-B2-concentration increased from 70 to 110 pg/ml three hours after endotoxin application in contrast to the control group. The fetuses in both groups did not show any significant changes during the experiments. The results indicate that prostaglandin F2 alpha is released as a special endotoxin effect in adult mini-pigs. Our measurements in the fetus make a direct endotoxin effect across the placenta unlikely. The fetuses of the mini-pigs, however, died as a result of the maternal cardio-vascular collaps.

Septicemia during pregnancy: a study in different species of experimental animals.

When Escherichia coli B6 lipopolysaccharide, 0.2 mg/kg of body weight, was infused into nonpregnant minipigs during a 5-hour period, the animals died after 12 to 16 hours as a result of endotoxic shock. When the same infusion was given to six pregnant minipigs at term, these animals died after only 3 1/2 hours. The decrease in the number of white blood cells, the number of platelets, hematocrit, and clotting factors was not significantly different between the two groups. The acid-base status, however, indicated a much more pronounced metabolic acidosis in the pregnant animals than in the nonpregnant controls. In the pregnant minipigs heart rate, cardiac output, mean arterial pressure, and total peripheral resistance indicated cardiovascular collapse, and the multiple wire, platinum surface electrode revealed a drastic reduction in uterine tissue oxygenation in the pregnant animals. The data support the hypothesis that pregnant animals at term are more susceptible to the harmful effects of lipopolysaccharide. Early death in the pregnant minipigs, however, was not associated with disseminated intravascular coagulation as it is in smaller animals (rat, rabbit, and hamster).

Characterization by Scatchard plots of monoclonal antibody enzyme conjugates directed against alpha-1-foetoprotein.

A radioimmunoassay was used to investigate the affinity of 2 monoclonal antibodies against human alpha-1-foetoprotein before and after conjugation with horseradish peroxidase. The equilibrium constant of the high-affinity antibody was reduced 10-fold whereas it remained unaffected in the low-affinity antibody. With the Scatchard diagram, quantification of unlabelled antibodies in the unpurified conjugate mixture is also possible if antibody affinity is changed by the coupling procedure.

[Long term experience with the IUD copper-T-200 (author's transl)]. / Langzeiterfahrungen mit dem Intrauterinpessar Cu-T-200.

During a period of seven years pregnancy-, expulsion- and extraction-rates of the copper-T-200 were determined for two different groups of patients in a university hospital. The first group were patients of the ambulatory care service representing an heterogenous composition. The other group were patients from a private practice representing a more homogenous population. In the first group insertions and controls were done by different physicians at various stages of their training, in the second group they were performed by an experienced clinician. In the first group there were 1397 primary IUD-insertions and 22,203 months of use, in the second group the corresponding data were 272 primary insertions an 5127 months of use. The pregnancy rates calculated according to the Pearl-index were 1.0 and 0.24, respectively. The expulsion rates were calculated as 0.8 and 0.2, respectively. The extraction rates because of unwanted side-effects were 4.4 in the first and 1.6 in the second group of patients. There seems to be an advantage in having the care of the IUD-patient being taken by an experienced physician, especially regarding the extraction rates because of unwanted side effects.

PIP: During a period of 7 years, pregnancy, expulsion, and extraction rates for the Copper T-200 were determined for 2 different groups of patients in a university hospital. The 1st group were patients on an ambulatory service care representing a heterogenous composition; the other group were patients from a private practice representing a more homogenous population. In the 1st group, insertions and controls were done by different physicians at various stages of their training; in the 2nd group they were performed by an experienced clinician. In the 1st group, there were 1397 primary IUD-insertions and 22,203 months of use, and in the 2nd group, the corresponding data were 272 primary insertions and 5127 months of use. The pregnancy rates calculated according to the Pearl index were 1.0 and 0.24 respectively. The expulsion rates were calculated as 0.8 and 0.2 and the extraction rates due to unwanted side effects were 4.4 in the 1st and 1.6 in the 2nd group. There seems to be an advantage in having the care of the IUD patient being taken on by an experienced physician, especially regarding the extraction rates due to side effects. (author's)

Portal venous thrombosis in ulcerative colitis: CT diagnosis with angiographic correlation.

A case of portal venous thrombosis in a patient with chronic ulcerative colitis is presented. Computed tomography correctly diagnosed the abnormality as confirmed by angiography.

[Results of the follow-up of the position of intra-uterine device by ultra-sonography (author's transl)]. / Ergebnisse der Lageüberwachung von Intrauterinpessaren durch Ultraschall.

The position of the intra-uterine device copper-T in 1372 women was followed up by ultrasound for four years. During this time 2565 ultrasound studies for the position of the intra-uterine device were carried out. The intra-uterine device was found in the cervix in 81 ultrasound investigations and removed or exchanged. In 12 cases the device was pushed back into the uterine cavity. 12 women became pregnant. This corresponds to a Pearl index 0.72 with a mean insertion time of 14.6 months and 20.000 patient-months of wearing of an intra-uterine device. In 9 of the 12 pregnant cases the device was found in the cervix. 6 of these patients reported only once instead of the projected four times for ultra-sound follow-up and the last normal ultrasound follow-up was usually nine months or longer ago. Our findings suggest that the contraceptive effectiveness of an intra-uterine device can be improved by regular ultra-sonic control of the position and can by approximated to the effectiveness of hormonal contraception.

PIP: A report of 2565 ultrasonic examinations of 1372 women to determine the position of a Copper T IUD is presented. The mean length of IUD use was 14.6 months. In 139 cases the IUD was found in an intracervical position; in 93 of these cases the position of the IUD in the cervix was verified by pelvic examination and reinserted or replaced in 81 cases. The pregnancy rate was 12 for 20,031 use-months, corresponding to a Pearl index of .72. In 9 of these 12 pregnancies, the IUD was found in the intracervical position, and in the majority of these cases the most recent ultrasonic examination had been done more than 6 months previously. A large number of IUDs were found in an intracervical position in the first 2 months after insertion. It is recommended that an ultrasonic examination to determine the position of an IUD be given a few days following the insertion, after each of the first 2 months following insertion, and every 3-6 months afterwards.