The correlation between occupation type and fibromyalgia severity.

BACKGROUND: Fibromyalgia (FM) is a chronic pain disorder associated with financial burden, decreased work productivity and absenteeism. Occupational stressors and specific employment factors may contribute to the severity of FM. AIMS: To determine if occupation type or employment status correlates with FM diagnostic and severity parameters, as assessed via validated instruments including tender points (TP), Widespread Pain Index (WPI), Symptom Severity (SS) and pain regions. METHODS: We performed a cross-sectional study of 200 adult patients diagnosed with FM at a single-centre FM clinic. Demographic and clinical data were extracted from the electronic medical records. Occupations were manually grouped in an iterative modified-Delphi approach and participants were grouped by employment status (Working, Not Working/Disabled or Retired) for analysis. RESULTS: In our cohort, 61% were employed and 24% were not working/disabled, while the remainder were students, homemakers or retired. SS score was significantly higher (P < 0.001) in not working/disabled patients compared to those employed. Business owners had the lowest TP count (median = 14) and the lowest median SS score (median = 7). WPI was highest for Others (Arts/Entertainment, Driver/Delivery and Housekeeper/Custodian workers; median=16) and the lowest for Retail/Sales/Wait Staff (median = 11). CONCLUSIONS: Work-related factors, occupation type and employment status correlate with diagnostic and severity parameters of FM. Employed participants had significantly lower SS scores suggesting that work loss correlates with SS. Participants employed in entry-level jobs or jobs with higher physical or financial stressors may experience greater FM symptoms. Further studies are required to explore work-related factors and their impact on the diagnostic and severity parameters of FM.

[Preservation of fertility in tumour patients]. / Erhaltung der Fertilität bei Tumorerkrankungen.

The success rates of present-day chemotherapy have provoked a rising awareness with regard to the preservation of quality of life among successfully treated patients. Among other factors, quality of life also implies the capacity to procreate. Unfortunately, both in men and women chemotherapy often irreversibly destroys the production of gametes, thereby causing permanent infertility. By its long-standing experience with the cryopreservation of oocytes, zygotes and embryos, reproductive medicine may offer assistance to those patients. Whereas the storage of cryopreserved semen has now become standard in most institutions, the options for the preservation of fertility in women suffering of malignant disease are still limited. Although cryopreservation of non-fertilized oocytes or of pronuclear cells has been established, both the number of oocytes that can be collected within the short time interval between the first detection of the tumour and the initiation of chemotherapy and the modest developmental capacity per frozen/thawed oocyte markedly limit the option of ovarian hyperstimulation and assisted reproduction. Several successful deliveries of healthy infants have now proven the feasibility of ovarian tissue cryopreservation and later orthotopic transplantation after successful tumour therapy. Further refinement of the techniques involved, but also the formation of multidisciplinary networks are expected to offer a solution for young women struck by cancer but striving to survive and to lead a fulfilled life.

Sentinel lymph node biopsy is associated with improved survival compared to level I & II axillary lymph node dissection in node negative breast cancer patients.

OBJECTIVE: The few long-term follow-up data for sentinel lymph node (SLN) negative breast cancer patients demonstrate a 5-year disease-free survival of 96-98%. It remains to be elucidated whether the more accurate SLN staging defines a more selective node negative patient group and whether this is associated with better overall and disease-free survival compared with level I & II axillary lymph node dissection (ALND). METHODS: Three-hundred and fifty-five consecutive node negative patients with early stage breast cancer (pT1 and pT2< or =3 cm, pN0/pN(SN)0) were assessed from our prospective database. Patients underwent either ALND (n=178) in 1990-1997 or SLN biopsy (n=177) in 1998-2004. All SLN were examined by step sectioning, stained with H&E and immunohistochemistry. Lymph nodes from ALND specimens were examined by standard H&E only. Neither immunohistochemistry nor step sections were performed in the analysis of ALND specimen. RESULTS: The median follow-up was 49 months in the SLN and 133 months in the ALND group. Patients in the SLN group had a significantly better disease-free (p=0.008) and overall survival (p=0.034). After adjusting for other prognostic factors in Cox proportional hazard regression analysis, SLN procedure was an independent predictor for improved disease-free (HR: 0.28, 95% CI: 0.10-0.73, p=0.009) and overall survival (HR: 0.34, 95% CI: 0.14-0.84, p=0.019). CONCLUSIONS: This is the first prospective analysis providing evidence that early stage breast cancer patients with a negative SLN have an improved disease-free and overall survival compared with node negative ALND patients. This is most likely due to a more accurate axillary staging in the SLN group.

Target and reality of adjuvant endocrine therapy in postmenopausal patients with invasive breast cancer.

Previous research evaluating the use of adjuvant endocrine therapy among postmenopausal breast cancer patients showed with 15-50% wide ranges of non-adherence rates. We evaluated this issue by analysing an unselected study group comprising of 325 postmenopausal women, diagnosed from 1997 to 2003 with hormonal receptor-positive invasive breast cancer. The different clinical situations that led to the discontinuation of adjuvant endocrine therapy were clearly defined and differentiated: non-adherence was not simply the act of stopping medication, but rather the manifestation of an intentional behaviour of the patient. Of the 287 patients who initiated endocrine therapy, 191 (66.6%) fully completed this treatment. Thirty-one patients (10.8%) showed non-adherence to therapy. Patients who had follow-up with a general practitioner, rather than in an oncologic unit, were more likely to be non-adherent (P=0.0088). Of 25 patients who changed medication due to therapy-related adverse effects, 20 (80%) patients fully completed the therapy after drug change. In adjuvant endocrine therapy, a lowering of the non-adherence rate to 10.8%, the lowest reported in the literature, is realistic when patients are cared for by a specialised oncologic unit focusing on the individual needs of the patients.

Levels of circulating cell-free serum DNA in benign and malignant breast lesions.

PURPOSES OF THE STUDY: We analyzed circulating cell-free DNA in the serum of patients with benign and malignant breast disease and in healthy individuals to determine its diagnostic value. BASIC PROCEDURES: Serum samples were obtained from 50 healthy individuals, 33 patients with malignant breast disease and 32 patients with benign breast disease. Circulatory DNA was extracted from serum samples. Cell-free DNA was quantified by real-time quantitative PCR for the glyceraldehyde-3-phosphate dehydrogenase (GAPDH) gene. Tissue samples from patients with malignant and benign breast lesions were histopathologically examined. MAIN FINDINGS: The mean levels of circulating cell-free DNA in serum samples were 41,149 genome equivalents (GE)/mL in patients with malignant disease, 30,826 GE/mL in patients with benign disease, and 13,267 GE/mL in healthy individuals. Healthy individuals had significantly lower levels of cell-free DNA than patients with malignant or benign breast disease (p=0.001, p=0.031). No significant difference was observed between malignant and benign disease. There was a correlation between cell-free DNA levels and tumor size but not with other tumor characteristics. PRINCIPAL CONCLUSION: Our results suggest that levels of circulating cell-free DNA in serum could have diagnostic value to discriminate between healthy individuals and patients with breast lesions but not between patients with malignant and benign breast lesions.

[Breast cancer with noninflammatory skin involvement: new data revise the traditional image of a "classical" clinicopathologic entity]. / Mammakarzinome mit nichtinflammatorischer Hautbeteiligung: Neue Daten revidieren das traditionelle Bild einer "klassischen" klinikopathologischen Entität.

Historically, the presence of skin involvement results in the classification of a breast carcinoma into the highest tumor category, or accordingly into the highest non-metastatic disease stage (current TNM classification: T4/stage III). However, probably the most important criterion of the TNM classification system is the basic rule that tumors exhibiting similar extension and prognosis should be grouped into one category. Newer studies indicate the need to revise the current TNM system, since grouping all tumors demonstrating "skin involvement" together results in the combination of tumors with widely differing prognostic and therapeutic implications into a single group. Thus, our recommendation is that breast carcinomas classified under the TNM categories T4a-c should be only grouped together according to tumor size. Only the prognostically very unfavorable inflammatory carcinomas (T4d) should be maintained in the T4 category.

Breast cancer sagittal/horizontal plane location influences axillary lymph node involvement.

AIM: To assess the influence of tumour location on axillary lymph node involvement (ALNI) and prognosis in breast cancer by evaluating the significance of the sagittal/horizontal alignment. METHODS: We compared 57 patients with superficially located breast carcinomas up to 3.0 cm with patients having lesions in posterior planes of the breast. Both groups were matched according to age, time of diagnosis, tumour size, grade, hormonal receptor status and tumour site within the frontal plane. Histologic evidence of skin involvement, excluding tumours fulfilling the criteria for pT4b, was defined as inclusion criteria and reference plane for superficial tumour location. RESULTS: Tumours situated in the superficial region of the breast, compared to those located in deeper planes, have an increased risk of ALNI (p=0.023), whereas no difference was observed with reference to disease-specific survival (p=0.203). CONCLUSION: This study shows that ALNI is dependent on sagittal/horizontal as well as frontal tumour location. Clinicians should be aware that tumours lying posteriorly may be at increased risk of occult spread outside axillary lymph nodes.

Scope and significance of non-uniform classification practices in breast cancer with non-inflammatory skin involvement: a clinicopathologic study and an international survey.

BACKGROUND: The study evaluates the scope of non-uniform classification practices concerning breast carcinomas with non-inflammatory skin involvement. PATIENTS AND METHODS: We compared the clinical course of patients with histologically proven non-inflammatory skin involvement: 119 (65.4%) with clinically obvious 'classical' skin changes (Group A) and 63 (34.6%) with no or only discreet changes (Group B). A questionnaire was circulated to pathology departments in 24 countries to assess the practice concerning the placement of skin- involved breast carcinomas in the TNM classification. RESULTS: Patients in Group B showed a significantly better disease specific survival (P=0.0002). Eighty-six respondents (70.5%) of the survey preferred the 'histological view' and classified tumors with only histological proven skin involvement as T 4 b/stage IIIB. The opposing classification principle ('clinical view'), which dictates that T 4 b breast cancer is a clinical diagnosis and the classical signs must be present, was supported by 31 respondents (25.4%). CONCLUSIONS: A large number of breast cancer patients with non-inflammatory skin involvement are only histologically proven and show, compared with cases exhibiting the classical clinical signs, significant differences in clinical course and prognosis. In general, both subsets were aggregated in one T category/stage (T 4 b/IIIB). This results in a considerable distortion of the reported statistical data.

[Chemotherapy for gynecological malignancies--a contraindication during pregnancy?]. / Chemotherapie bei gynäkologischen Tumoren--kontraindiziert in der Schwangerschaft?

Even though a malignant tumor during pregnancy is very rare it occurs in 0.02-0.1%. With the tendency in society to postpone childbirth to an older age, there will be more cancers diagnosed during pregnancy. The coincidence of malignant disease with pregnancy leads to an enormous emotional burden to the patient, the couple and the medical staff. Surgery for malignant tumors during pregnancy seems to be save. Radiotherapy on the other hand should be avoided. Chemotherapy is regarded to be save during the second and third trimester but it should not be applied during the first trimester because of its teratogenic effects. The most frequent malignant disorders during pregnancy are cervical cancer, breast cancer, melanoma and Hodgkin lymphoma. We discuss possible treatment options for breast cancer and gynecological tumors during pregnancy. Ovarian Cancer is a rare event during pregnancy. Because of frequent prenatal visits most of them are diagnosed at an early stage, with good prognosis. In case of advanced stage of ovarian cancer chemotherapy besides surgery is necessary. The former usually is preferred as monotherapy during pregnancy. To treat breast cancer during pregnancy a mastectomy with axillary lymphonodectomy is necessary to avoid radiotherapy. Indications for chemotherapy are the same as for not pregnant patients. Usually AC with and without 5-FU is used. For invasive cervical cancer surgery or radiotherapy +/- chemotherapy is indicated after induced abortion or cesarean section. Early termination of pregnancy is of no survival benefit to the mother in case of breast cancer and ovarian cancer. In these cases systemic therapy during pregnancy and delivery at 34 weeks is recommended.

[Ultrasound endometrium follow-up during tamoxifen treatment: Really not reliable or useful after all?]. / Sonographische Endometriumkontrolle unter Tamoxifen: Wirklich nicht empfehlenswert oder doch sinnvoll?

AIM: To investigate whether an examination of the endometrium of women treated with tamoxifen (TAM) is useful or not. METHOD: 40 breast cancer patients who displayed a thickened endometrium of > 8 mm and/or vaginal bleeding were included in the study. They received daily TAM adjuvantly. Histologic clarification by hysteroscopy and D&C was recommended for patients with an endometrium of > 8 mm or vaginal bleeding. RESULTS: In our collective, the mean endometrial thickness was 13.7 +/- 5.6 mm (SD). 32 patients underwent a histological examination. Most had a benign lesion; in 2 cases we merely found a cystic atrophy (11 mm, 18 mm), 2 displayed atypical tissue (13 mm, 25 mm) and 2 an endometrial cancer (19 mm, 33 mm). All patients with atypical tissue or cancer had an endometrial thickness markedly above the norm, but 3 of them were not bleeding. No linear correlation between thickness of the endometrium and duration of TAM intake was found. CONCLUSION: To detect early premalignant or malignant changes of the endometrium, we recommend histological examination by hysteroscopy and dilatation and curettage when the endometrium is > 8 mm thick, even in the absence of symptoms. Therefore, these patients should have regular examinations by transvaginal ultrasound once or twice a year. Moreover, continuing regular screening of the endometrium for years after termination of tamoxifen-therapy is also to be recommended.

[Neurofibromatosis of the breast in a patient with Morbus von Recklinghausen]. / Neurofibromatose der Brust bei Morbus von Recklinghausen.

Neurofibromatosis is a rare autosomal dominant disorder with several subtypes. Common is the appearance of specific skin alterations. Neurofibromas occurring in the breast are very rare, and in such cases they are most common in the areolar area. A case of a 46-year-old woman with von Recklinghausen's disease of the breast is reported, and the literature will be discussed.

Aging, serum estradiol levels, and pregnancy differentially affect vascular reactivity of the rat uterine artery.

OBJECTIVES: To investigate the effects of aging, ovarian ablation, and pregnancy on vascular reactivity of the rat uterine artery. METHODS: Segments of uterine artery from 3-month-old pregnant and nonpregnant Wistar rats and from aged and ovariectomized animals, both 9 months of age, were exposed in vitro to vasoactive mediators. Absolute contractile force as well as endothelium-dependent and -independent vascular reactivity were determined. Isometric tension was recorded using a modified Mulvany myograph system. Results were compared with analysis of variance and Bonferroni-Dunn post hoc analysis and correlated with serum estradiol levels. RESULTS: Aging up to 9 months decreased absolute tension of uterine arteries in vitro elicited by KCl (P < .0001), while not affecting receptor-operated responses to norepinephrine, endothelin-1, and angiotensin II. After ovarian ablation maximal contraction to norepinephrine was selectively reduced in the aged animal (P = .0053). Pregnancy increased absolute tension to KCl (P < .0001), norepinephrine (P < .008), and endothelin-1 (P = .0003), whereas relative contractile force (percentage of KCl) induced by norepinephrine and endothelin-1 remained unchanged and that induced by angiotension II decreased (P = .0001) in pregnant animals. In addition, pregnancy increased sensitivity to the endothelium-dependent vasodilator acetylcholine (P = .0022) but decreased that to the endothelium-independent vasodilator sodium nitroprusside (P = .0062). Endothelium-dependent relaxation correlated with serum estrogen levels remained unchanged in 9-month-old Wistar rats, which physiologically exhibited high serum estrogen concentrations but was impaired with regard to both maximum relaxation (P < .0001) and sensitivity in aged rats (P = .0007) after ovariectomy. CONCLUSIONS: Vascular contractility is impaired in the uterine artery of the aged rat as evidenced by reduced responses to KCl, whereas responses to receptor-operated agonists remain unchanged. Functional ovaries are essential to preserve endothelium-dependent relaxation in aging animals. During pregnancy, contractile machinery and endothelium-dependent relaxation are enhanced. In contrast, contractions to angiotensin II and endothelium-independent relaxation to sodium nitroprusside are reduced in late pregnancy. These changes in reactivity of the uterine artery may be important for the regulation of blood flow in the uterus according to physiologic needs.

Primary carcinoma of the fallopian tube. A report of 19 cases with literature review.

Primary carcinoma of the fallopian tube is the rarest cancer of the female genital tract with an incidence of 0.5% of all gynecologic tumors. Since the first report in 1847 about 1,500 cases have been published. Due to similarity of the clinical presentation the staging and therapeutic management have been adapted to that of ovarian cancer. We retrospectively evaluated all the 19 patients who had been diagnosed with primary carcinoma of the fallopian tube at the Department of Obstetrics and Gynecology of the University of Zurich between 1977 and 1998. All lesions were staged according to the rules of FIGO adopted in 1991. At the time of diagnosis the median age was 62 (46-87) years. Twelve (63%) women revealed FIGO stage III-IV, whereas four (21%) and three (16%) patients were diagnosed in stage I and stage II, respectively. Eight (42%) women were nullipara. Histology showed serous-papillary carcinoma, in ten (53%) cases. The 5-year survival rate was 22% for all FIGO stages and 80% for stage I. None of the patients with stage III and IV survived 5 years. Ovarian cancer and primary carcinoma of the fallopian tube are similar in many aspects. Both carcinomas have a similar age distribution, show an increase among nulliparous women, are often of serous papillary histology, have a poor prognosis with stage and residual tumor size as important prognostic factors, and respond initially well to platinum-based chemotherapy. Nevertheless, there appears to be a difference between the two diseases: primary carcinoma of the fallopian tube is more often diagnosed in an earlier stage. This many be due to lower abdominal pain resulting from tubal dilatation and to abnormal bloody-watery discharge.

Curative radiotherapy in elderly patients with endometrial cancer. Patterns of relapse, toxicity and quality of life.

PURPOSE: To assess survival, disease-specific survival, acute and late toxicity and quality of life in patients with curable endometrial carcinoma treated with adjuvant or primary radiotherapy at the age > or = 75 years. PATIENTS AND METHODS: In a prospective study, outcome was regularly assessed in 49 patients treated between 1991 and 1995 at a median age of 78.4 years. Radiotherapy was applied using the same concept as in younger patients. Thirty-eight patients received postoperative adjuvant radiotherapy (vaginal insertions only: n = 18; external and vaginal insertions: n = 17; external radiotherapy only: n = 3), 8 patients were treated for a vaginal recurrence. Three patients received primary radiotherapy. Median pelvic dose was 39.6 Gy (ICRU) with 1.8 Gy per fraction (4 fields). Vaginal HDR radiotherapy consisted of 5 times 5 Gy at 0.5 cm depth in cases with no external radiotherapy, and of 3 times 5 Gy in addition to pelvic radiotherapy, respectively. Median follow-up was 3.2 years. The EORTC QLQ-C30 was used for self-assessment of quality of life. RESULTS: Survival and disease-specific survival at 5 years was 64% and 84%, respectively. There was no pelvic or vaginal recurrence in patients with Stage IA to IIB. Patients with positive adnexa and those treated for vaginal recurrence relapsed in 50%. Two patients (4%) did not complete radiotherapy because of severe diarrhea. Grade 4 late complications were observed in 1/38 patients following adjuvant radiotherapy and in 2/8 patients treated for a recurrence. The actuarial rate of Grade 3 to 4 complications was 7% at 3 years. Quality of life was good in most cases and remained constant over time. CONCLUSIONS: Elderly patients with endometrial cancer may be treated following the same guidelines as younger patients. Radiotherapy for a vaginal recurrence is less effective and more toxic.

[Chemotherapy of endometrial cancer revisited]. / Stellenwert der Chemotherapie in der Behandlung des Endometriumkarzinoms.

The current status and future directions of chemotherapy in the management of endometrial cancer are reviewed. For patients with advanced or recurrent endometrial carcinoma the most active single drugs are doxorubicin, epirubicin, cisplatin, carboplatin, paclitaxel, ifosfamide, 5-fluorouracil and vincristine with response rates ranging from 18 to 36%. Data at the present time support the conclusion that if chemotherapy is indicated a combination of doxorubicin + cisplatin is the standard chemotherapy for patients with advanced or recurrent endometrial carcinoma and yields a response rate of 47-60%. A first trial using a combination of these drugs with paclitaxel promises an increase in response rate to 73%, but data regarding prolongation of survival are not yet available. Up to now the benefit of neither chemotherapy nor endocrine therapy could be established in the adjuvant setting.

[Gynecological infections in general practice]. / Gynäkologische Infekte in der Praxis.

Although infections of the lower female genital tract are common, they only rarely pose diagnostic and therapeutic problems for the experienced clinician. If there is no response to primary therapy, however, or in cases of recurrence further steps are indicated. Sexually transmitted diseases are characterized by common involvement of the upper genital tract by ascending infection. Appropriate therapeutic measures including treatment of the partner are important in order to prevent severe acute and chronic diseases.

Chronic blockade of nitric oxide synthase and endothelin receptors during pregnancy in the rat: effect on reactivity of the uterine artery in vitro.

OBJECTIVE: To investigate the effects of chronic blockade of nitric oxide (NO) production and endothelin (ET-1) receptor antagonism on endothelial and vascular smooth muscle function of the uterine artery in vitro obtained from nonpregnant and pregnant rats. METHODS: Pregnant or nonpregnant Wistar rats were either treated orally for up to 18 days with the NO synthase inhibitor N omega-nitro-L-arginine methyl ester (L-NAME), the ETA-/ET beta-receptor antagonist bosentan, or both, or they received no treatment (controls). Absolute contractile force as well as endothelium-dependent and -independent vascular reactivity of uterine arteries were determined in vitro. Isometric tension was recorded. ANOVA and the Mann-Whitney U test were used for statistical analysis. RESULTS: Pregnancy increased absolute tension (mN/mm) elicited in uterine arteries by ET-1 (P < .01), serotonin (P < .05), norepinephrine (P < .02), and KCl (P < .0001). Chronic treatment with L-NAME or L-NAME plus bosentan, but not with bosentan alone, reduced contractions to KCl in pregnant and nonpregnant rats (P < .005-.0001), while pregnancy-induced enhancement in tension development remained unchanged in all groups (P < .005). After exposure of uterine arteries to L-NAME in vitro, vascular sensitivity to ET-1 was augmented in uterine arteries of pregnant but not of nonpregnant animals (P < .05). L-NAME-pretreatment did not influence the pregnancy-induced increase of vascular sensitivity to acetylcholine but reduced maximal relaxation in nonpregnant animals (P < .05). In addition, pregnancy diminished sensitivity of uterine arteries to sodium nitroprusside (P < .002), which was abolished by chronically administered L-NAME. Bosentan had no influence on vasodilation in vitro. CONCLUSION: Neither endothelin-1 nor nitric oxide seem to contribute to the augmented tension to depolarization and receptor-operated stimulation of vascular smooth muscle cells in rat uterine arteries during pregnancy. In addition, pregnancy is associated with increased NO production in uterine arteries, as evidenced by augmented endothelium-dependent relaxations, increased NO release by endothelin-1, and decreased sensitivity to sodium nitroprusside.

Pulmonary atresia with ventricular septal defect: a case for central venous pressure and oxygen saturation monitoring.

A 21-year-old patient with pulmonary atresia and ventricular septal defect (PA-VSD) was admitted to the hospital for tubal ligation. Invasive arterial and central venous (CVP) pressure, pulse oximetric oxygen saturation (SpO2), and (from the tip of oximetric central venous catheter) central venous oxygen saturation (ScvO2) and oxygen extraction rate (ExO2) were continuously monitored. Heart rate (range: 68-75 beat/min), mean arterial pressure (80-90 mmHg), CVP (7-10 mmHg), SpO2 (79-90 percent), ScvO2 (57-70 percent), and ExO2 (21-30 percent) remained stable during epidural anesthesia and transvaginal sterilization. Following an overnight stay (peak SpO2 92 percent; peak ScvO2 71 percent; through ExO2 21 percent), the oxygen data returned to baseline on awakening (SpO2 < 80 percent, ScvO2 < 55 percent, ExO2 > 35 percent), and the patient was discharged. In PA-VSD, a single-outlet double-ventricle anomaly, CVP reflects the preload of systemic ventricle. As the mixed venous oxygen saturation cannot be defined, ScvO2 is the best available indicator of the whole body oxygen consumption. Continuous monitoring of CVP, ScvO2 and ExO2 in the superior vena cava may provide more insight into the response to anesthesia and surgery in patients with PA-VSD.