100 years of iodine testing of the cervix: A critical review and implications for the future.

OBJECTIVES: We aim to describe the history of iodine testing of the cervix and identify areas where further work is required. STUDY DESIGN: We conducted a search of PubMed and Google Scholar. Full article texts were reviewed. Reference lists were screened for additional articles and books. 37 basic articles in journals including ones written in German and three basic articles in books were identified. RESULTS: Glycogen staining of the ectocervical squamous epithelium with iodine goes back to Paul Ehrlich (1854-1915). Walter Schiller (1887-1960) examined nearly 200 different dyes and found that vital staining of the cervical squamous epithelium was best achieved with Lugol's iodine solution, which was indicated by Jean Guillaume Lugol (1786-1851) for disinfection of the vagina. In 1928 W. Lahm observed that the glycogen content of a squamous epithelium cell decreases as anaplasia increases. From the outset, H. Hinselmann included the iodine test in the minimum requirements for colposcopy. In 1946 H. J. Wespi first mentioned the finding of an "uncharacteristic iodine negative area." The first international colposcopic terminology from Graz in 1975 lists the "iodine light area" among the different colposcopy findings. The IFCPC nomenclatures from Rome 1990, Barcelona 2002, and Rio de Janeiro 2011 have evaluated the iodine test and classified their findings differently. A breakthrough to effective cervical cancer screening in resource-limited settings in Africa, India, and Latin America was achieved with R. Sankaranarayanan's publication on naked-eye visual inspection of the cervix after application of Lugol's iodine. CONCLUSIONS: This paper is a step toward a better understanding of what we think and do today with iodine testing and what problems and upcoming tasks will arise in future.

200 years of diagnosis and treatment of cervical precancer.

OBJECTIVES: The history of the diagnosis and treatment of cervical precancer is fragmentary. Findings in the English-speaking and German-speaking areas vary considerably. We aim to describe the history of clinical advances in diagnosis and treatment of cervical precancer and identify areas where further work is required. STUDY DESIGN: We conducted a search of PubMed and Google Scholar. Full article texts were reviewed. Reference lists were screened for additional articles and books. 9 basic articles in German and 13 basic articles in books were identified. RESULTS: The first images of the ectocervix were published by H. Lebert (1812-1879) in the middle of the nineteenth century. R. Meyer's (1864-1947) theory of erosions, which dominated cervical pathology in the nineteenth century, was later refuted in studies by C. A. Ruge (1846-1926) and J. Veit (1852-1917). In 1908 W. Schauenstein (1870-1943) recognized the step-by-step development of cervical cancer. H. Hinselmann (1884-1959) replaced the purely histopathological approach previously with the use of colposcopy. All conization methods applied today can be traced back to amputation of the ectocervix as first indicated by J. Marion Sims (1813-1883) in 1861. In 1928 M. N. Hyams was the first to describe an excision method that employed electrodiathermy. The method of cold knife conization is based on a publication by J.W. Scott from 1957. The final breakthrough to effective electrodiathermy was achieved with the publications of W. Prendiville. CONCLUSIONS: This paper is a step toward a better understanding of what we think and do today based on past findings of colposcopists and gynecopathologists.

Has there been a change in peripartal maternal mortality in a tertiary care obstetric European center over the last five decades?

OBJECTIVE: Maternal mortality still remains a significant problem in obstetrics worldwide. Unchanged or even rising maternal mortality has been reported in several countries. The present study analyzed whether the pattern of maternal mortality has changed over the last five decades at the Department of Obstetrics and Gynecology of the Medical University of Graz. STUDY DESIGN: Starting in 1981, a registry of maternal deaths was established and regularly updated at our institution based on retrospective data. Between 1963 and 2012, a total of 187,917 women delivered. Thirty-five consecutive maternal deaths were observed and subdivided into 10 year cohorts. METHODS: The registry of maternal deaths included deliveries after 28+0 weeks of gestation. Puerperal deaths were defined as deaths up to day 42 post partum. MAIN OUTCOME MEASURES: Clinical data from maternal deaths were extracted from hospital records and autopsy reports. RESULTS: Maternal mortality rates declined from 35.0, 29.0, 2.4, 13.1 to 3.6 per 100,000 deliveries in the five subsequent periods, respectively. Sixty-six percent of women who died were 30 years or older. The cesarean section rate was 49%. Ninety-one percent of the 35 maternal deaths occurred in women with no significant medical history or risk factors. Seventy-five percent of deaths occurred after the 37+0 weeks of gestation. During all study periods, the prevalence of infections and hemorrhage was highest. The main causes of bleeding were uterine rupture and placental abruption, respectively. CONCLUSION: Even nowadays, peripartal maternal deaths occur mainly due to infections and hemorrhage and also in women with no significant medical history.

Hermann Lebert (1813-1878): a pioneer of diagnostic pathology.

Hermann Lebert (1813-1879) was a pioneer of diagnostic pathology and medical iconography. He was born in Breslau, then Prussia, and died in Nice (France). He lived in Switzerland as a general physician, in France as a pathologist, and eventually became the chairman for internal medicine in Zurich and Breslau, respectively. The significance of Hermann Lebert for medical posterity has three aspects: firstly, scientific linking of the French (Parisian) school and its distinctive clinical/practical orientation to the later clinical/pathological German school of Johann Lukas Schönlein, Johannes Müller, and Rudolf Virchow; secondly, his pioneering of the diagnostic use of the microscope in pathological anatomy; and finally, his remarkable book, Traité d'anatomie pathologique générale et spéciale, which has almost fallen into oblivion, being unknown to most contemporary workers.

Why do human papillomavirus infections induce sharply demarcated lesions of the cervix?

Chronic infections with high-risk human papilloma virus (HPV) have been established to cause cervical cancer. The causal pathogenesis of cervical carcinoma is believed to be the result of the proliferation of one or, at most, a few HPV-transformed cells. So far, it has not been possible to identify and analyze these early initial lesions or cell clusters. Invasive cervical cancer arises in cervical intraepithelial neoplasia, which in turn develops preferentially in squamous metaplasia in clearly demarcated fields. These fields are the main salient morphologic characteristic in cervical intraepithelial neoplasia and can be recognized colposcopically as well as histomorphologically. The precise mechanism for the development of separate, well-delineated fields in HPV-related intraepithelial neoplasia and the variable susceptibility of stem or reserve cells for different HPV genotypes remains unsolved. In cervical carcinogenesis, the link between formal pathogenesis apparent as colposcopic and histomorphologic changes and the causal pathogenesis of HPV-induced genetic changes is still missing and an issue for future research.

Cervical intraepithelial neoplasia III: long-term follow-up after cold-knife conization with involved margins.

OBJECTIVE: To evaluate the long-term outcome of patients with severe cervical intraepithelial neoplasia (CIN) III or squamous carcinoma in situ after cold-knife conization with involved margins. METHODS: A total of 390 patients (median age 39 years, range 20-69) with positive margins after cold-knife conization for CIN III were followed expectantly for a mean of 19 (range 6-30) years. Follow-up consisted of colposcopy, cytology, histology, and pelvic examination. RESULTS: Overall, 306 (78%) patients remained free of CIN III, and 84 (22%) had persisting or recurrent CIN III (n = 78) or developed invasive carcinoma (n = 6). Fifty-three patients had persisting CIN III (diagnosed within 1 year of conization), 25 developed recurrent CIN III after a median of 3 (range 2-28) years, five developed microinvasive carcinomas (at 3, 6, 7, 12, and 23 years), and one developed a stage IB carcinoma at 8 years. Persisting or recurrent disease was more common in patients in whom both the endocervical and the ectocervical cone margins were involved than in those in whom only the ectocervical or the endocervical margin was positive (52% versus 17% and 21%, respectively, P <.001). CONCLUSION: Expectant management is reasonable for patients with CIN III and positive margins after cold-knife conization. However, these patients require careful follow-up, particularly during the first year.

Parametrial spread of cervical cancer in patients with negative pelvic lymph nodes.

OBJECTIVE: We studied the incidence and prognostic implications of parametrial involvement according to tumor volume in a series of cervical cancer patients with negative pelvic lymph nodes. METHODS: We reviewed a series of 351 node-negative patients with stage IB, IIA, or IIB cervical cancer treated with class III radical hysterectomy. The surgical specimens were processed as step-serial giant sections and tumor volume was calculated. Overall, 180 patients had tumors <5 mL, 120 had tumors of 5-20 mL, and 51 had tumors >20 mL. Parametrial involvement was classified as continuous, discontinuous, or involvement of blood vessels or lymph nodes and according to location as medial or lateral. A total of 302 patients had squamous cell tumors and 49 had adenocarcinomas. The mean duration of follow-up was 9.3 years. RESULTS: Overall, 44 of 351 patients (12.5%) had parametrial involvement. The rate of parametrial involvement in patients with tumors <5, 5-20, and >20 mL was 6.7, 12.5, and 33%, respectively. Isolated involvement of the medial parametrium increased with tumor size (3.8, 8.3, and 27.5%, respectively), whereas isolated involvement of the lateral parametrium was seen in 2.2, 1.6, and 0% of the cases. Involvement of both the medial and the lateral portions of the parametrium was seen in 0.5, 2.5, and 5.9% of the specimens, respectively. There were no differences in the rate of parametrial involvement between squamous cell carcinomas and adenocarcinomas. The 5-year disease-free survival rates in patients without or with parametrial involvement were 90.2% vs 90%, 91.7% vs 92.9%, and 84.7% vs 67%, respectively. CONCLUSION: The lateral portion of the parametrium can be involved in patients with cervical cancer and negative pelvic lymph nodes, but this is uncommon. In this series of patients treated with type III radical hysterectomy, parametrial involvement had no influence on disease-free survival.