Late radiotherapeutic morbidity in patients with carcinoma of the uterine cervix: the application of the French-Italian glossary.

BACKGROUND AND PURPOSE: The aim of this study was to perform a retrospective analysis of the complications observed and the importance of delayed symptoms for radiotherapeutic morbidity in patients treated by radiotherapy alone for cervical cancer. MATERIALS AND METHODS: From 1979 to 1991, 145 patients with primary uterine cervical cancer were treated with external radiotherapy and intracavitary applications. During the follow-up, all signs, symptoms and therapy of late treatment complications were recorded. Complications were graded according to the French-Italian glossary. This glossary is used for recording morbidity after treatment of gynaecological cancer. RESULTS: Overall, 119 late complications were recorded. They were most frequently located in the gastro-intestinal system (53%) with a median time to development of 9 months. Urinary complications were recorded in 20%. Very few complications were recorded in vagina/uterus (12%) and pelvic soft tissue (5%). The probability of surviving without tumour recurrence and/or late combined moderate to severe organ morbidity decreased with increasing FIGO stage. CONCLUSIONS: For reporting gynaecological morbidity, the French-Italian glossary is useful. Treatment optimization must take into account actuarial estimates of survival and morbidity.

An office semiquantitative serum human chorionic gonadotropin determination.

OBJECTIVE: To compare the human chorionic gonadotropin (hCG) concentration, established by a standard serum quantitative hCG fluorescent immunoassay and a semiquantitative serum determination. DESIGN: Patients were asked to give two serum samples early in pregnancy to establish the accuracy of a semiquantitative serum hCG test in diluted and undiluted serum samples. SETTING: In a laboratory setting, two serum samples were determined; one sample was submitted for standard serum hCG radioimmunoassay, and the other was tested for hCG by the 25 IU Tandem ICON Assay (Hybritech, Liege, Belgium) in diluted and undiluted serum samples. PARTICIPANTS: Sixteen patients supposed to be pregnant. MAIN OUTCOME MEASURES: Within dilutional zones, the results of a semiquantitative hCG test were compared with a known standard quantitative serum hCG immunoassay measurements. RESULT: The semiquantitative hCG ranges of serum hCG compare fairly well with an accurate standard quantitative serum hCG immunoassay. CONCLUSION: The determination of a serum hCG range compares well with the standard quantitative serum hCG immunoassay (First International Reference Preparation) and can be completed within 15 minutes. This office semiquantitative serum hCG determination proved to be a quick and reliable test.

Treatment of tubal pregnancy by local injection of methotrexate after adrenaline injection into the mesosalpinx: a report of 25 patients.

Twenty-five patients with a tubal pregnancy were treated by an injection of methotrexate (MTX) into the tubal swelling after vasoconstriction of the mesosalpinx with adrenaline. Twenty-four of the 25 patients had an uneventful clinical course. In one case, the tube ruptured despite falling serum human chorionic gonadotropin (hCG) concentrations. In 17 of 24 patients, the dose of 100 mg that was locally injected was sufficient. Seven patients were given additional systemic injections. In 3 of the 4 patients with high initial serum hCG levels (greater than 10.000 mIU/mL), the clinical course was uneventful. The side effects of MTX and adrenaline were minimal. Whether this way of treatment guarantees better chances of fertility in the future is unknown. Therefore a prospective, case-controlled study comparing the fertility rates in different ways of treatment is needed.

Histopathology of five tubes after treatment with methotrexate for a tubal pregnancy.

OBJECTIVE: To investigate whether treatment with a local high dose of methotrexate (MTX) for a tubal pregnancy hampers tubal repair. DESIGN: From a total of 67 cases treated with MTX for their tubal pregnancy, two tubes ruptured shortly after the MTX injection and were removed. One patient insisted on a removal of the affected tube in spite of the fact that serum human chorionic gonadotropin was negative. Two patients had her tube removed +/- 1 year after the MTX treatment during a salpingo-oophorectomy because of endometriosis and cystic enlarged ovary. RESULTS: In the ruptured tubes there were no findings supporting the idea that tubal rupture occurred because of the injection of MTX into the tube. There were also no signs of a hampered tubal-tissue response to the insult of invading chorionic tissue. Macroscopic and microscopic evaluation of the unruptured tubes showed no residual tubal destruction. In the tubal wall, all layers were normal and continuous, all unruptured tubes were gracile without distention. CONCLUSION: Methotrexate applied in a high local dose does not seem to hamper tubal response against the insult of invading chorionic tissue or to interfere with the ultimate tubal repair.

A review of the literature on nonsurgical treatment in tubal pregnancies.

In some cases tubal pregnancy resolves spontaneously. The risk of subsequent surgical intervention due to either tubal rupture or the entry criteria of the study varies from 0 per cent to 31 per cent. The major problem in nonsurgical treatment of tubal pregnancy is the absence of a parameter that reveals the threat of tubal rupture. In addition, data on the functional recovery of the fallopian tube are controversial. The scarcity of data on medical treatment with RU486, glucose 50 per cent, KCL, and actinomycin-D make proper evaluation impossible. Both MTX and prostaglandin treatment should be investigated further. Compiled data on prostaglandin treatment in cases of unruptured tubal pregnancy do not show better results than data on expectant management only. If, however, patients with initial serum hCG levels greater than 1000 mIU/ml or greater than 2500 mIU/ml are excluded from this therapy, the risk of tubal rupture diminishes. Side effects are minimal, especially if injection into the corpus luteum is omitted. Compiled data on MTX treatment in cases of unruptured tubal pregnancy show a crude risk of subsequent surgical intervention of 5 per cent. If patients with an initial serum hCG level exceeding 10,000 mIU/ml are excluded, the risk of tubal rupture is limited to 3 per cent. (The estimated risk of persistent trophoblastic activity after conservative surgical therapy is also 5 per cent.) Studies on the optimum MTX dosage, treatment scheme, and method of administration are still going on. Side effects are reversible and minimal. Theoretically, the local injection of MTX is more effective. Although often used to propagate a new way of treatment, fertility in the future is a questionable parameter in the evaluation of therapy. Fertility is influenced by so many factors other than the method of treatment that it can only be used for treatment evaluation in a case control or a randomized prospective study. Such a study has yet to be published. Besides the influence on future fertility, other results of treatment, such as morbidity, cost, and length of hospital stay should be taken into account.

Graves' disease during pregnancy.

Presented are two case studies which investigate the adverse effects of Graves' disease in pregnant women. Particular attention has been paid to the therapeutic regimen and its implications for the maternal, fetal and neonatal well-being. The first case study illustrates that Graves' disease complicating pregnancy can be treated by bed rest and careful observation of mother and fetus. The first pregnancy of our second case study confirms these results. Her second pregnancy, in which the symptoms of Graves' disease were far more severe, illustrates that it is possible to treat fetal hyperthyroidism by treating the pregnant mother with antithyroid drugs. If great care is taken to avoid overtreatment of the fetus, the treatment with antithyroid drugs is superior to surgical treatment, since surgery completely neglects the problem of fetal hyperthyroidism.

Observations on intra-uterine resting-phase pressure in at term pregnancy in different body positions.

Investigations were conducted into the influence of body position on intra-uterine resting phase pressure in women in labour. A micro pressure sensor was placed in the uterus and rectum of 14 women immediately after artificial rupture of the fetal membranes. A significant increase in the intra-uterine resting-phase pressure was experienced when the body position was changed from supine to sitting and also from supine to standing. The intrarectal pressure, a parameter of the intra-abdominal pressure, also showed this significant increase by the same magnitude. The increased resing-phase pressure in the uterus, when the women are in a standing or sitting position, is therefore the result of extra-uterine factors.

Treatment of ectopic pregnancy with methotrexate.

This is a report on the successful treatment of an unruptured tubal pregnancy with methotrexate (MTX). To our knowledge eighteen cases, including ours, have been reported in Western literature so far. The advantages and drawbacks of this therapy are discussed.

Surfactant in the amniotic fluid and bromhexine metabolite VIII.

The effect of metabolite VIII of bromhexine on surfactant content in the amniotic fluid was investigated in a double blind study. Administration of 100 and 200 mg NA-872 daily for 5 days to pregnant women ranging in gestational age from 196 to 243 days was not followed by a significant rise in the L/S ratio.

A review of prognostic factors in early-stage carcinoma of the cervix (FIGO I B and II A) and implications for treatment strategy.

Several prognostic factors in stages I B and II A cervical carcinoma have been widely studied to define groups of patients with a poor prognosis. Most of these factors are interrelated. The characteristics which should be regarded as main factors have not yet been defined, because the studies reported were based on mainly retrospective and non-randomized analysis. Reviewing the literature, lymph node metastasis, differentiation grade, tumor size, parametrial extension, lymph-blood vessel invasion and cervical invasion seem to be prognostically important factors, which suggests that the subdivision of patients according to the FIGO classification alone is inaccurate. It seems useful to define subgroups of patients according to tumor characteristics, determined after surgical treatment and accurate histologic examination of the surgical specimen. Patients with one or more of these tumor features need additional treatment to improve survival. The current treatment modalities, such as postoperative radiotherapy, have not been thoroughly evaluated, but doubt exists as to their efficacy. Data in the literature suggest that particularly patients with para-aortic or multiple pelvic lymph node metastasis (greater than 3) have already developed distant metastases at the time of primary treatment and therefore need adjuvant systemic therapy. Patients with tumors larger than 4 cm in diameter, differentiation grade III, lymph-blood vessel invasion or cervical invasion (of more than 70%) seem to have high recurrence rates at both pelvic and distant sites, indicating that there is also a need for better pelvic control.

[Extrauterine pregnancy in Netherlands: patient characteristics, treatment, and pregnancy prognosis]. / Extra-uteriene graviditeit in Nederland: patiëntkenmerken, behandeling en zwangerschapsprognose.

OBJECTIVE: To determine the probability of pregnancy after a finished extrauterine pregnancy (EUP) and the length of time in between. DESIGN: Prospective multicentric cohort study. METHOD: Of all patients with an EUP between May 1990 and October 1993, data were collected using a questionnaire from surgeons in five university hospitals and 30 general training and non-training hospitals. During the subsequent 3 years, the patients semi-annually reported on their pregnancy or wish to become pregnant using reply cards. RESULTS: A total of 665 patients with an EUP were reported their mean age was 30.7 years (SD: 4.9). There were 341 patients who during the follow-up desired pregnancy, did not start an IVF procedure and supplied complete follow-up data 207 of them (61%) became pregnant after a median interval of 12 months. Age above 35, previous fertility problems, a Chlamydia antibody titre > or = 1:64 and adnexitis in the anamnesis were correlated with a longer interval until a subsequent pregnancy. The nature of the treatment (laparotomy versus laparoscopy, conservative versus radical and surgical versus pharmaceutical) did not affect the duration of the interval. If the contralateral tube was judged to be abnormal by the operator, pregnancy was still possible, but the occurrence of the pregnancy was delayed. CONCLUSION: The probability of pregnancy after an earlier EUP averages 61%; the interval until the next pregnancy, if any, depends mostly on factors that cannot be influenced at the time of the diagnosis of EUP.

[Extrapulmonary tuberculosis in 3 Dutch patients]. / Extrapulmonale tuberculose bij drie Nederlandse patiënten.

In three patients, two women aged 71 and 59 years and a man aged 49 who had been living in the Netherlands for a long time and who were admitted because of vague symptoms, extrapulmonary manifestations of tuberculosis were diagnosed: tuberculosis of the lumbar spine with psoas abscess, tuberculous peritonitis and adrenal tuberculosis with Addison's disease in a patient with open pulmonary tuberculosis. All three recovered with tuberculostatic therapy (isoniazid, streptomycin, pyrazinamide and rifampicin).

The evaluation of postoperative irradiation in patients with early-stage ovarian cancer.

This is a retrospective study of 127 patients with ovarian carcinoma stage I, II, and III with no or minimal residual disease postoperatively. Patients were treated with radiotherapy by the moving strip technique from 1970 through 1984. The 5-year actuarial survival rate was 73%. Analysis was made on subgroups such as a complete versus incomplete staging procedure, stage, histopathology, grade, and amount of residual tumor. In this study, grade is a significant prognostic indicator (survival in grade 1 versus grade 2 and 3 tumors was statistically different (P less than 0.005). Stage 1 and 2 patients do better than stage 3 patients. Residual tumor does not influence survival rate. The disease-free survival of patients with serous cystadenocarcinoma is better than that of patients with mucinous cystadenocarcinoma (P less than 0.004). The incidence of severe complications was 4%.