Arnim A. Bader

Anhydramnios associated with administration of trastuzumab and paclitaxel for metastatic breast cancer during pregnancy

A 38-year-old women in her second pregnancy presented with symptomatic metastatic spinal-cord compression 7 years after undergoing lumpectomy and axillary dissection for stage I primary breast cancer. Immunohistochemistry analysis of the tumour had shown that it was oestrogen-receptor negative, progesterone-receptor positive, and overexpressed ERBB2. The patient had received six cycles of cyclophosphamide, methotrexate, and fl uorouracil followed by radiotherapy and then tamoxifen, which she had taken for 5 years. 86 months after primary diagnosis the patient developed paresthesia and hypoesthesia of the left arm and pain in the cervical vertebrae. MRI showed diff use metastatic infi ltration of the corpus of the second cervical vertebra (fi gure 1) with spinal-cord compression. Additional lesions in the fourth thoracic vertebra and the left femur were also seen with bone scintigraphy, but no other signs of metastatic disease were identifi ed by clinical examination, chest radiograph, or abdominal ultrasound. At this time the patient was 17 weeks pregnant with normal fetal development. After counselling the patient decided to continue pregnancy and was started on hydromorphone hydrochloride. Palliative radiotherapy of 46 Gy given in 23 fractions was administered to the cervical vertebra, which resulted in clinically improved neurological symptoms and pain. Cervical radiotherapy was undertaken with lead shielding of the uterus to protect the fetus. At 25+6 weeks’ gestation the patient received trastuzumab (8 mg/kg loading dose) combined with 175 mg/m of paclitaxel, followed by another cycle at 28+5 weeks with the dose of trastuzumab reduced to 6 mg/kg and the dose of paclitaxel kept the same. Close fetal surveillance was undertaken. Between 26 weeks’ gestation and 32 weeks’ gestation, during two cycles of trastuzumab and paclitaxel, fetal abdominal circumference stopped increasing and the volume of amniotic fl uid decreased to almost anhydramnios (fi gure 2). The mother was of normal constitutional size with normal weight gain of 11 kg during pregnancy and no other risk factors for restriction of intrauterine growth. Tests for premature rupture of the membranes were negative. At 31+6 weeks the volume of both fetal kidneys was decreased below the fi fth percentile. Additionally, the urinary bladder was barely visible, suggesting reduced renal function, and doppler sonography showed increased resistance indices of both the renal arteries (fi gure 3). Doppler sonography of the fetal umbilical and maternal uterine arteries was normal, which suggested healthy placental function. Serial ultrasound measurements of femur length, biparietal diameter, and head circumference were all within normal limits. As a result of the evidence of fetal renal failure and cessation of abdominal growth, fetal lung maturation was induced with corticosteroids after two cycles of trastuzumab and paclitaxel, and a caesarean section was done at 32+1 weeks’ gestation. The male newborn infant weighed 1460 g (tenth percentile), had a body length of 39 cm, and had a head circumference of 29.5 cm. The pH value of the umbilical artery was 7.31. The placenta weighed 290 g and placental histology was normal. The newborn infant showed signs of bacterial sepsis with hypotension, transient renal failure, respiratory failure necessitating mechanical ventilation, and positive laboratory fi ndings (C-reactive protein 30 mg/dL). With antibiotic treatment blood pressure normalised after 2 days and mechanical ventilation was ended on day 6. Diuresis was adequate with serum creatinine slightly increased (1.6 mg/dL) until day 14. Ultrasonography of the fetal kidneys showed transient hyperechodensities in the renal parenchyma that resolved by day 28. These transient hyperechodensities are often noted in newborn infants with transient renal failure as a result of decreased renal perfusion. Echocardiography and cranial ultrasound examinations were normal. The infant was discharged at age 6 weeks weighing 2335 g and in healthy condition. Development at 12 weeks was normal. Lancet Oncol 2007; 8: 79–81

T1 breast cancer: identification of patients at low risk of axillary lymph node metastases.

AbstractObjective. The status of the axillary lymph nodes is one of the most important prognostic factors in patients with breast cancer. A panel of molecular markers of tumor aggressiveness in addition to conventional clinical and histopathologic features were analyzed in an attempt to identify a subgroup of patients with a low risk of axillary lymph node metastases. Material and methods. Data from 358 patients with T1 breast cancer who underwent level I/II axillary lymph node dissection (ALND) were investigated. Hormone receptor status, Ki-67, S-phase fraction, DNA ploidy, HER-2/neu, p53, epidermal growth factor receptor, urokinase type plasminogen activator, plasminogen activator inhibitor-1, bone marrow micrometastases as well as patient age, menopausal status, tumor site, tumor size, histologic type, tumor grade, carcinoma in situ, multifocality, and lymph vascular invasion (LVI) were studied to predict axillary lymph node status. Results. In a multivariate logistic regression analysis LVI (present v.s. not present), Ki-67 (≥18% v.s. <18%), tumor size (1.1–2 cm v.s. ≤1 cm), and histologic grade (G3 v.s. G1/2) were identified as independent predictive factors of axillary lymph node metastases. Approximately 13% of patients (n = 47) with well or moderately differentiated tumors less than or equal to 1 cm, no lymph vascular invasion, and a low Ki-67 staining were identified as having a low risk of axillary lymph node metastases of 4.3%. However, 20 patients with all four unfavorable predictive factors had a 75% incidence of axillary lymph node involvement. Conclusion. Primary tumor characteristics can be used to identify a subgroup of patients with a low risk of axillary lymph node metastases in T1 breast cancer. Preoperative risk assessment might be used to omit routine ALND in those patients at low risk of axillary lymph node metastases.

Neonatal outcome and two-year follow-up after expectant management of second trimester rupture of membranes

Objective: To assess neonatal outcome and 2‐year follow‐up of pregnancies complicated by second trimester preterm premature rupture of membranes (PPROM). Methods: A retrospective review of obstetric and neonatal records for 87 pregnancies (56 singletons, 6 twins, 1 triplet) with PPROM between 14 + 0 and 24 + 6 weeks of gestation. Patients received antibiotics and steroids for fetal lung maturity once they reached 24 weeks of gestation. Placentas were examined histopathologically. Surviving infants were followed‐up at 2 years of age. Results: Median latency from PPROM to delivery was 4 days. Survival rate of 56 singletons was 45% (25/56); and 13 died in hospital. Survival rate of infants discharged from hospital was 23% (12/56). Chorioamnionitis was seen histologically in 42% (5/12) of surviving infants compared with 92% (12/13) of those that died in hospital. Of the 12 surviving infants, 50% had a normal neurological and developmental outcome at 2 years of age. Conclusion: Gestational age, birth weight, and histologic chorioamnionitis have prognostic importance in pregnancies complicated by PPROM. Surviving infants have a 50% chance of achieving an adequate health status at 2 years of age.

How accurate is frozen section histology of pelvic lymph nodes in patients with endometrial cancer

OBJECTIVE Recent prospective data support the trend towards systematic retroperitoneal lymphadenectomy in patients with high-risk endometrial cancer. Because para-aortic node involvement in the absence of pelvic node involvement is uncommon, a reliable finding of negative pelvic lymph nodes (PLN) at intraoperative frozen section examination might allow omitting para-aortic dissection. We analyzed the diagnostic accuracy of frozen section examination of PLN in patients with endometrial cancer. METHODS We reviewed 131 patients with endometrial cancer who underwent surgery including systematic pelvic lymphadenectomy (n=101) or pelvic and para-aortic lymphadenectomy (n=27). Intraoperative frozen section examination of PLN was performed in 72 (55%) patients. Results of frozen section examination were compared with those of final histopathology and the diagnostic accuracy of frozen section examination of PLN was calculated. One pathologist measured the diameters of PLN metastases retrospectively. RESULTS A total of 1063 and 2666 PLN were analyzed by frozen section examination and by final histopathology, respectively. PLN metastases were found in 7 cases (10%) at frozen section examination, and in 17 cases (24%) at final histopathology (false negative rate, 59%). No false positive cases were noted. The mean diameter of all PLN metastases at final histopathology was 4.3 mm, as compared to 9.0 mm for the metastases detected at frozen section analyses. The mean diameter of PLN metastases missed at frozen section examination was 2.0 mm. CONCLUSION In this review at a single institution, intraoperative frozen section histology missed nearly two of three endometrial cancer patients with positive nodes. These results do not support tailoring the extent of lymphadenectomy according to the results of frozen section examination.

Assessment of risk factors for survival of neonates born after second-trimester PPROM.

OBJECTIVE Assess fetal risk factors which impact survival of infants delivered after second-trimester PPROM. STUDY DESIGN Clinical records of 87 patients, who all had second-trimester rupture of membranes between 14+0 and 24+6 weeks of gestation treated January 1998 to July 2005 were reviewed regarding perinatal outcome. This study is based on 25 surviving infants. RESULTS 13 of these 25 infants died in the hospital. Survivors had a higher birth weight (p=0.008) and higher Apgar scores after 5 min (p=0.005) than those infants dying. No differences in UA pH, the need of catecholamines and no association between histological verified chorioamnionitis and early onset sepsis were seen between survivors and nonsurvivors. CONCLUSION Higher gestational age at birth, higher birth weight, the absence of histologically verified chorioamnionitis and 5 min Apgar scores of >or= than 6 have positive prognostic value for survival of neonates delivered preterm after second-trimester PPROM.

Guideline: Überwachung und Management bei Überschreitung des Geburtstermins1

Aufbauend auf der «evidence-based medicine» sollen Guidelines eine Hilfeleistung und Orientierung für Diagnostik und Therapie der individuellen Patientin erbringen. Die FMH legt Wert darauf, dass Guidelines insbesondere für die Ärzte in der Praxis, aber auch für den klinischen Bereich ihre Anwendung finden sollen. «Leitlinien» sind systematisch entwickelte Darstellungen und Empfehlungen mit dem Zweck, Arzt und Patientin bei der Entscheidung über zweckdienliche Massnahmen der Krankenversicherung (Prävention, Diagnostik, Therapie und Nachbehandlung) unter spezifischen klinischen Umständen zu unterstützen. Leitlinien stellen den Stand des Wissens über effektive und zweckdienliche Krankenversorgung zum Zeitpunkt der Veröffentlichung dar und wenden sich in erster Linie an den ärztlichen Bereich, erst sekundär an die Öffentlichkeit und die Versicherer. Wegen der Fortschritte der wissenschaftlichen Erkenntnisse müssen Leitlinien periodisch überarbeitet werden. Die Entscheidung darüber, ob einer bestimmten Empfehlung gefolgt werden soll, muss vom Arzt unter Berücksichtigung der bei der individuellen Patientin vorliegenden Gegebenheiten und der verfügbaren Ressourcen entschieden werden. Im Einzelfall müssen somit die aktuelle Situation der Patientin, ihr Umfeld, ihre sozio-ökonomische Situation, die Komorbidität und Nebendiagnosen, aber auch ihre ethische und religiöse Haltung mitberücksichtigt werden. Damit ist ein entscheidender ärztlicher Freiraum gegeben, welcher es überhaupt ermöglicht, Leitlinien in die Praxis umzusetzen. «Therapeutische Freiheit» bedeutet, dass der Arzt sowohl die Kompetenz hat wie auch die Verantwortung dafür trägt, dass die von ihm an der Patientin vorgenommene Diagnostik bzw. durchgeführte Therapie dem aktuellen Stand der Wissenschaft entspricht – therapeutische Freiheit somit gleichermassen als Freiheit wie auch als Verpflichtung, das Richtige zu tun.

Inflammatory myofibroblastic tumour of the urinary bladder mimicking recurrent uterine carcinosarcoma.

Inflammatory myofibroblastic tumours (IMTs) are rare benign or locally recurrent soft tissue tumours. The most common sites of origin are the lung, mesentery and omentum. Other sites include the gastrointestinal tract, genitourinary tract, skin, breast, and central nervous system. Most IMTs occur in the first two decades of life, and women are affected slightly more than men. Synonyms for the term IMT include plasma cell granuloma, inflammatory pseudotumour and inflammatory myofibrohistiocytic proliferation. Inflammatory fibrosarcoma is a close relative in the current World Health Organization classification of soft tissue tumours. Histologically, IMTs are characterized by proliferation of myofibroblastic spindle cells accompanied by an inflammatory infiltrate of plasma cells, lymphocytes and eosinophilic granulocytes. The differential diagnosis includes other mesenchymal tumours such as uterine neoplasms, particularly carcinosarcomas. We describe an inflammatory myofibroplastic tumour of the urinary bladder closely mimicking recurrent carcinosarcoma.

Die Tension-free-vaginal-tape-Operation zur Behandlung der Stressinkontinenz

Die neueste Entwicklung in der chirurgischen Therapie der weiblichen Stressinkontinenz ist die Tension-free-vaginal-tape (TVT)-Operation und analoge Verfahren. Im Unterschied zur Kolposuspension nach Burch und abdominovaginalen Schlingenoperationen ist das Ziel des TVTs eine Stabilisierung der mittleren Urethra, nicht eine Reposition des Blasenhalses. In der einzigen Studie, die das neue Verfahren gegen den bisherigen Standard, der Kolposuspension nach Burch, randomisiert hat, sind die 2-Jahres-Kontinenzraten der TVT-Operation durchaus mit denen der Kolposuspension nach Burch vergleichbar. Die TVT-Operation dürfte sich aufgrund der technisch einfachen Durchführung, der niedrigen Rate an intra- und postoperativen Komplikationen sowie der guten Kontinenzraten als Standardverfahren in der Behandlung der primären und Rezidivstressinkontinenz etablieren.

Wie wurde das Endometriumkarzinom 2011 diagnostiziert

Hintergrund: Die Abklarung von postmenopausalen Frauen mit vaginaler Blutung oder sonographisch auffalligem Endometrium ist kontroversiell. Empfehlungen von Fachgesellschaften reichen von Transvaginalsonografie und Endometriumbiopsie hin zu Hysteroskopie und fraktionierter Curettage. Material und Methode: Wir untersuchten die Diagnostik bei allen 89 Patientinnen mit Erstdiagnose eines Endometriumkarzinoms (EC) an der UFK Graz im Zeitraum 2010 – 11. Die Auswertung erfolgte hinsichtlich der primaren Symptomatik („presenting symptom“) sowie der diagnostischen Herangehensweise. Wir verglichen Patientinnen die bereits mit der Diagnose EC zur Therapie zugewiesen wurden mit Patientinnen mit Diagnose im Haus. Die Ergebnisse wurden Vergleichsdaten aus 2005 gegenubergestellt. Ergebnisse: Bei 69 Fallen (78%) trat eine Blutung als Erstsymptom auf, bei 8 (9%) erfolgte die Abklarung ausschlieslich auf Grund einer auffalligen Sonografie, bei 2 Fallen mit Ovarialkarzinom (3%) wurde das EC als Zusatzbefund in einem HE-Praparat gefunden, wahrend bei 4 (5%) die weitere Diagnostik aufgrund eines PAP V veranlasst wurde. 5 Patientinnen wurden mit bereits metastasiertem EC vorstellig. 41 Patientinnen (46%) wurden mit bereits diagnostizertem EC zugewiesen, bei 48 (54%) erfolgte die ED im Haus. Ein sonographisch auffalliges Endometrium wurde in 58 Falle (67%) dokumentiert, was einem Anteil von 74% (n = 46) Patientinnen mit auffalligem Endometrium bei primarer Abklarung wegen BPMP entspricht. Die Tabelle zeigt die Methode der Diagnosesicherung in Abhangigkeit vom Diagnoseort. Die diagnostischen Herangehensweisen unterschieden sich signifikant (p < 0,0001). Diskussion: Knapp die Halfte der 2010 – 11 intern diagnostizierten Endometriumkarzinome wurde mit Endometriumbiopsie diagnostiziert, womit diesen Patientinnen die HSK/Curettage erspart werden konnte. Die Methodik der Diagnosesicherung zeigt deutliche Unterschiede abhangig vom Standort, wobei die im niedergelassenen und peripheren Bereich festgestellten Endometriumkarzinome uberwiegend per HSK/Curettage festgestellt wurden. Die Verteilung der „presenting symptoms“ entspricht den in der Literatur angegebenen Vergleichszahl (Dijkhuizen P. et al, Cancer 2000; 89(5), 1765 – 1772) sowie hausinternen Daten aus 2005. Nur 8 Falle (9%) wurden ausschlieslich auf Grund einer auffalligen Sonografie detektiert.

Maligne Tumoren der Vulva

Maligne Veranderungen der Vulva sind selten. Die Inzidenz eines Vulvakarzinoms betragt 2/100.000 Frauen/Jahr. Der Altersgipfel fur das invasive Karzinom liegt zwischen dem 70. und 80. Lebensjahr, wahrend vulvare intraepitheliale Neoplasien (insbesondere VIN III) vorwiegend zwischen dem 35. und 40. Lebensjahr diagnostiziert werden.