Frank Girardi

Patterns of pelvic and paraaortic lymph node involvement in ovarian cancer

One hundred eighty patients with ovarian cancer underwent complete pelvic lymphadenectomy (n = 75) or pelvic and paraaortic lymphadenectomy (n = 105). Twenty-one patients underwent a preoperative biopsy of the scalene lymph nodes. The incidence of positive lymph nodes was 24% in stage I (n = 37), 50% in stage II (n = 14), 74% in stage III (n = 114), and 73% in stage IV (n = 15). Of the 105 patients who underwent pelvic and paraaortic lymphadenectomy, 13 (12%) had positive pelvic and negative paraaortic nodes and 10 (9%) had positive paraaortic and negative pelvic nodes. Positive scalene nodes were found in four patients (19%) later shown to have stage IV disease. One hundred forty patients were studied for number of involved nodes and node groups, size of nodal metastases, residual tumor, and survival. Of the 81 patients with positive nodes, most had only one or two positive node groups or one to three positive individual nodes. A few patients had seven to eight involved node groups with up to 44 positive nodes. Greater numbers of positive nodes were found in stage III than stage IV. The size of the largest nodal metastasis was not related to the clinical stage or survival, but did correlate with the number of positive nodes. Stage III patients with no residual tumor had a significantly lower rate of lymph node involvement than those with tumor residual (P less than 0.01). Actuarial 5-year survival rates of patients with stage III disease and no, one, or more than one positive nodes were 69, 58, and 28%, respectively.

The importance of parametrial lymph nodes in the treatment of cervical cancer

This study aimed to determine the presence, distribution, and metastatic involvement of lymph nodes in the parametria of patients undergoing radical hysterectomy for cervical cancer. Parametrial nodes were present in the giant sections of 280 (78%) of 359 surgical specimens, and metastatically involved nodes were found in 63 (22.5%) of these 280. Both positive and negative nodes were distributed through the entire parametrium. The frequency of positive nodes was linearly associated with both the clinical stage and with the tumor volume. The recurrence rate was higher when the parametrial nodes were positive than when they were negative. Survival dropped when the parametrial nodes were positive, regardless of the clinical stage.

Microinvasive carcinoma of the uterine cervix (International Federation of Gynecology and Obstetrics Stage IA).

In 1985 the International Federation of Gynecology and Obstetrics (FIGO) subdivided Stage IA cervical cancer and specified metric criteria to demarcate Stage IA from Stage IB. Early stromal invasion (Stage IA1) denotes the first invasive protrusions of a carcinoma in situ into the stroma. Microcarcinomas (Stage IA2) are small cancers a number of orders of magnitude larger than Stage IA1 lesions and with a maximum depth of invasion of 5 mm and a maximum horizontal spread of 7 mm; larger lesions are classified as Stage IB. This study reviews 486 patients previously classified as having Stage IA disease. This yielded 344 Stage IA1 and 101 Stage IA2 lesions; 41 cancers were reclassified as Stage IB. Three hundred nine, 89, and 38 patients were followed for ± 5 years. One (0.3%) patient with Stage IA1 disease re‐presented with Stage IIB disease 12 years after conization. Five (5.6%) patients with Stage IA2 lesions developed invasive recurrences; three died. None of the 38 patients reclassified as having a Stage IB lesion, including 16 who were treated conservatively, developed a recurrence. The FIGO classification is not a guideline for treatment. Stage IA1 lesions can be treated conservatively, but treatment in Stage IA2 must be individualized. Risk factors such as vascular space involvement and confluency are of high sensitivity but low specificity.

Prognostic importance of human papillomavirus type 16 DNA in cervical cancer.

Human papillomavirus (HPV) type 16 DNA is frequent in invasive cervical cancers. Among 43 patients with invasive cervical cancer, HPV‐16‐positive tumors spread to the parametrial and pelvic lymph nodes significantly more often than did HPV‐16‐negative tumors (P < 0.05). Demonstration of HPV‐16 DNA in invasive cervical cancers may be an additional prognostic factor for this disease.

Cell differentiation-related gene expression of human papillomavirus 33

The gene expression of human papillomavirus (HPV) 33, which can be detected both in benign and malignant genital tumors, was analyzed in a cervical condyloma acuminatum by in situ hybridization using open reading frame-specific RNA probes. Viral mRNA concentrations increased with the degree of differentiation of the keratinocytes. The probes for reading frames E4 and E5 generated the most intense signals. The patterns of the specific viral mRNAs were very similar to those in condylomas induced by HPV 6 or 11, which are only rarely associated with malignancies. This implies that in tumors of the same degree of morphological differentiation the gene expression program of different HPV types is essentially identical. The pattern observed here most likely corresponds to a productive phase of viral infection.

Diagnosis and surgical treatment of cervical cancer

9. 10. Introduction Natural history 2.1. Morphologic aspects 2.2. The role of human papillomaviruses 2.3. The transition to invasive growth Colposcopy 3.1. Cytology and colposcopy 3.2. Cervicography Histologic evaluation Morphometry Imaging techniques 6.1. Ultrasonography 6.2. Computed tomography 6.3. Magnetic resonance imaging 6.4. Comparative studies of imaging techniques 6.5. MRI tumormetry 6.6. Lymph node involvement Spread to the lymph nodes Clinical staging 8.1. Stage1 8.1.1. Stage Ia 8.1.2. Stage Ib 8.2. Stage II 8.2.1. Stage IIa 8.2.2. Stage IIb 8.3. Stage IIIa Staging laparotomy Surgical treatment 10.1. 10.2. 10.3. 10.4. Principles Local radicality Lymphadenectomy Treatment according to stage 10.4.1. Cervical intraepithelial neoplasia 10.4.2. Microinvasive carcinoma 10.4.2.1. Stage Ial 10.4.2.2. Stage Ia 182 182 182 184 186 187 190 191 192 193 195 195 195 195 195 195 196 197 199 199 199 201 201 201 201 202 202 202 202 202 204 204 204 205 205 205

Messerkonisation versus Loop-Excision – klinische und histomorphologische Ergebnisse

In einer prospektiv randomisierten Studie wurden die histomorphologischen und klinischen Ergebnisse der Messerkonisation (n = 52) und der Loop-Excision (n = 38) miteinander verglichen. Alle PrApa

Microinvasive Carcinoma of the Uterine Cervix (International Federation of Gynecology and Obstetrics Stage IA)

In 1985 the International Federation of Gynecology and Obstetrics (FIGO) subdivided Stage IA cervical cancer and specified metric criteria to demarcate Stage IA from Stage IB. Early stromal invasion (Stage IA1) denotes the first invasive protrusions of a carcinoma in situ into the stroma. Microcarcinomas (Stage IA2) are small cancers a number of orders of magnitude larger than Stage IA1 lesions and with a maximum depth of invasion of 5 mm and a maximum horizontal spread of 7 mm; larger lesions are classified as Stage IB. This study reviews 486 patients previously classified as having Stage IA disease. This yielded 344 Stage IA1 and 101 Stage IA2 lesions; 41 cancers were reclassified as Stage IB. Three hundred nine, 89, and 38 patients were followed for greater than or equal to 5 years. One (0.3%) patient with Stage IA1 disease re-presented with Stage IIB disease 12 years after conization. Five (5.6%) patients with Stage IA2 lesions developed invasive recurrences; three died. None of the 38 patients reclassified as having a Stage IB lesion, including 16 who were treated conservatively, developed a recurrence. The FIGO classification is not a guideline for treatment. Stage IA1 lesions can be treated conservatively, but treatment in Stage IA2 must be individualized. Risk factors such as vascular space involvement and confluency are of high sensitivity but low specificity.

Quantification of Cellular Proliferation and Differentiation by Microphotometry of DNA and Protein

Both histochemical DNA staining with 3-hydroxy-2-naphthoic acid hydrazide and Fast Blue B, and the histochemical protein staining with 2-hydroxy-l-naphtaldehyde were used for DNA-protein double staining of different cells and tissues after being optimized and quantified. Integrated nuclear extinctions were determined simultaneously at the absorption maximum of DNA staining (550 nm) and the absorption maximum of protein staining (420 nm) by scanning microphotometry. The DNA protein scattergrams obtained were used for the characterization and quantification of cellular proliferation and differentiation. Differentiation was investigated with squamous epithelium of sections from human uterine cervix and with rat liver parenchymal cells isolated at different times after birth. Differentiation was shown to be accompanied by a characteristic increase of nuclear proteins relative to DNA. Dedifferentiation was investigated with rat liver cells grown under proliferation promoting conditions. In contrast to differentiating cells cellular dedifferentiation is accompanied by a characteristic decrease of nuclear proteins. Analysis of DNA protein scattergrams obtained from double stained sections of human uterine cervix, breast and liver revealed the existence of three subgroups of malignant tumors. Analysis of DNA-protein scattergrams of basal cells of the normal squamous epithelium of human uterine cervix also showed a “cfield effect” of adjacent tumors. A characteristic change of the DNA protein scattergram of basal cells in the vicinity of malignant tumors enabled the discrimination of corresponding cells of healthy volunteers.

Die Konisation non in sano

Prof. Dr. M. Lahousen, Geburtsh.-gynäkol. Univers.-Klinik, Auenbruggerplatz 14, A-8036 Graz Die scharfe Konisation ist in erster Linie ein diagnostischer und erst ein zweiter ein therapeutischer Eingriff. Die Indikation ergibt sich aufgrund einer mittels Biopsie gesicherten epithelialen Atypie, bis zum Verdacht auf Beginn des invasiven Wachstums. Geringe Dys-plasie und suspekte Smears, die über einen längeren Zeitraum persi-stieren, stellen eine weitere Indikation dar. Erfolgte die Abtragung der atypischen Epithelveränderung im Gesunden, ist die Diagnose und damit auch die Therapie erreicht. Unklar dagegen ist das weitere Vorgehen, wenn die Entfernung der Veränderung unvollständig, non in sano, erfolgte. Verlaufen die Schnittränder eines Konus nicht über-all durch gesundes Zervixgewebe muß damit gerechnet werden, daß an dieser Stelle eine zervikale intraepitheliale Neoplasie (CIN) zu-rückbleibt. Dazu kommt das Problem der Nachsorge, wenn die atypi-sche Veränderung an der Ektozervix oder im Zervikalkanal lokali-siert ist. Es erhebt sich daher die Frage, ob bei dem Befund, Konisation non in sano, eine weitere Operation oder ein konservatives Vorgehen indiziert ist. In den Jahren 1970 bis 1990 wurde an der Grazer Klinik bei 3663 Patientinnen mit der Diagnose CIN III eine Konisation durchgeführt. Die jüngste Patientin war 15 Jahre, die älteste 84 Jahre alt. Die Tech-nik der Schnittführung richtete sich nach der Lokalisation der Veränderung. Ein hoher Konus muß bei der Lokalisation der Veränderung im Zervikalkanal, ein flacher Konus bei Veränderung an der Zervix-außenfläche durchgeführt werden. Die Hämostase wird mittels Elektrokoagulation nach Herausschneiden des Konus erreicht. Ganz wichtig ist die aufwendige histologische Aufarbeitung. Nur damit ist es möglich festzustellen, ob die gesamte atypische Veränderung ent-fernt worden ist. Alle Frauen wurden in der Nachsorgeambulanz der Klinik engmaschig nachkontrolliert. Die Kontrolluntersuchung umfaßt die Kolposkopie, die Zytologie und die gynäkologische Palpation. Erfolgte die Konisation non in sano, so wurde eine Biopsie und/ oder eine Zervikalkanalcurettage durchgeführt. Die Untersuchungs-intervalle betrugen im ersten Jahr 3 Monate, danach ein halbes Jahr. Ab dem 5. Jahr erfolgt die Kontrolle jährlich. Bei 3663 Frauen mit der Diagnose CIN III erfolgte bei 2984 (82 %) die Konisation im Gesunden. In einem Zeitraum von 5-7 Jahren konnte in 8 Fallen ein neuerliches Auftreten von CIN III festge-stellt werden. Bei 669 Patientinnen (18 %) erfolgte die Konisation nicht im Gesunden. In 345 der Fälle (52%) lag die Veränderung zervikalwärts, bei 262 (39 %) peripher und bei 62 (9 %) peripher und zervikalwärts nicht im Gesunden. Aufgrund der inadäquaten Therapie wurde bei 228 Frauen (34%) ohne Kinderwunsch oder nach abgeschlossener Familienplanung die Hysterektomie durchgeführt. Das durchschnitt-liche Alter lag bei diesen Patientinnen bei 45 Jahren. Dabei