[Neurodevelopmental follow-up of premature children in Lausanne and Geneva]. / Suivi neurodéveloppemental de l'enfant né prématuré dans l'Arc lémanique.

Preterm children born before 32 weeks of gestation represent 1% of the annual births in Switzerland, and are the most at risk of neurodevelopmental disabilities. A neurological surveillance is thus implemented in the neonatal units, and multidisciplinary neurodevelopmental follow-up is offered to all our preterm patients. The follow-up clinics of the University hospitals in Lausanne and Geneva follow the Swiss guidelines for follow-up. An extended history and neurological examination is taken at each appointment, and a standardized test of development is performed. These examinations, which take place between the ages of 3 months and 9 years old, allow the early identification and treatment of developmental disorders frequent in this population, such as motor, cognitive or behavioral disorders, as well as the monitoring of the quality of neonatal care.

Structural asymmetries of perisylvian regions in the preterm newborn.

During the last trimester of human pregnancy, the cerebral cortex of foetuses becomes greatly and quickly gyrified, and post-mortem studies have demonstrated that hemispheres are already asymmetric at the level of Heschl gyrus, planum temporale and superior temporal sulcus (STS). Recently, magnetic resonance imaging (MRI) and dedicated post-processing tools enabled the quantitative study of brain development non-invasively in the preterm newborn. However, previous investigations were conducted either over the whole brain or in specific sulci. These approaches may consequently fail to highlight most cerebral sites, where anatomical landmarks are hard to delineate among individuals. In this cross-sectional study, we aimed to blindly and automatically map early asymmetries over the immature cortex. Voxel-based analyses of cortical and white matter masks were performed over a group of 25 newborns from 26 to 36 weeks of gestational age. Inter-individual variations associated with increasing age were first detected in large cerebral regions, with a prevalence of the right hemisphere in comparison with the left. Asymmetries were further highlighted in three specific cortical regions. Confirming previous studies, we observed deeper STS on the right side and larger posterior region of the sylvian fissure on the left side, close to planum temporale. For the first time, we also detected larger anterior region of the sylvian fissure on the left side, close to Broca's region. This study demonstrated that perisylvian regions are the only regions to be asymmetric from early on, suggesting their anatomical specificity for the emergence of functional lateralization in language processing prior to language exposure.

Hormone receptor expression in uterine sarcomas: prognostic and therapeutic roles.

OBJECTIVES.: The utility of hormone therapy in the management of uterine sarcomas is poorly defined. We hypothesize that estrogen receptor (ER) expression is common in uterine sarcomas, and carries prognostic significance. Further, we hypothesize that ER-positive uterine sarcomas respond to hormone therapy. METHODS.: We retrospectively reviewed charts of patients with uterine sarcomas. Stepwise Cox proportional hazards regression model was used to evaluate variables related to the risk of death: age, histology, stage, use of pelvic radiotherapy, and ER expression. In addition, we examined clinical outcomes in patients treated with aromatase inhibitors, megestrol acetate, depot medroxyprogesterone acetate, and tamoxifen. RESULTS.: Fifty-four patients underwent immunohistochemical staining, and 34 (63%) were ER-positive. Kaplan-Meier survival analysis and log-rank test indicated that patients with ER-positive sarcomas demonstrated improved overall survival when compared with ER-negative patients (median OS 36 vs. 16 months, p=0.004). Upon multivariate analysis, ER positivity retained significance as an independent predictor of survival (HR=0.32, CI 0.12-0.89, p=0.03). Four patients received hormonal treatment in the adjuvant setting and remained in remission (range of follow up: 18-68 months). Eighteen patients received hormone therapy in the setting of recurrent or progressive disease: fourteen (78%) demonstrated stable disease or complete or partial response (range of follow up: 6-124 months). CONCLUSIONS.: ER expression is common and is associated with improved overall survival in uterine sarcomas. Conducting immunohistochemical staining to ascertain ER status may aid with prognostication in this disease. Hormone therapy should be considered in patients with primary and recurrent ER-positive uterine sarcomas.

Primary cortical folding in the human newborn: an early marker of later functional development.

In the human brain, the morphology of cortical gyri and sulci is complex and variable among individuals, and it may reflect pathological functioning with specific abnormalities observed in certain developmental and neuropsychiatric disorders. Since cortical folding occurs early during brain development, these structural abnormalities might be present long before the appearance of functional symptoms. So far, the precise mechanisms responsible for such alteration in the convolution pattern during intra-uterine or post-natal development are still poorly understood. Here we compared anatomical and functional brain development in vivo among 45 premature newborns who experienced different intra-uterine environments: 22 normal singletons, 12 twins and 11 newborns with intrauterine growth restriction (IUGR). Using magnetic resonance imaging (MRI) and dedicated post-processing tools, we investigated early disturbances in cortical formation at birth, over the developmental period critical for the emergence of convolutions (26-36 weeks of gestational age), and defined early 'endophenotypes' of sulcal development. We demonstrated that twins have a delayed but harmonious maturation, with reduced surface and sulcation index compared to singletons, whereas the gyrification of IUGR newborns is discordant to the normal developmental trajectory, with a more pronounced reduction of surface in relation to the sulcation index compared to normal newborns. Furthermore, we showed that these structural measurements of the brain at birth are predictors of infants' outcome at term equivalent age, for MRI-based cerebral volumes and neurobehavioural development evaluated with the assessment of preterm infant's behaviour (APIB).

Mapping the early cortical folding process in the preterm newborn brain.

In the developing human brain, the cortical sulci formation is a complex process starting from 14 weeks of gestation onward. The potential influence of underlying mechanisms (genetic, epigenetic, mechanical or environmental) is still poorly understood, because reliable quantification in vivo of the early folding is lacking. In this study, we investigate the sulcal emergence noninvasively in 35 preterm newborns, by applying dedicated postprocessing tools to magnetic resonance images acquired shortly after birth over a developmental period critical for the human cortex maturation (26-36 weeks of age). Through the original three-dimensional reconstruction of the interface between developing cortex and white matter and correlation with volumetric measurements, we document early sulcation in vivo, and quantify changes with age, gender, and the presence of small white matter lesions. We observe a trend towards lower cortical surface, smaller cortex, and white matter volumes, but equivalent sulcation in females compared with males. By precisely mapping the sulci, we highlight interindividual variability in time appearance and interhemispherical asymmetries, with a larger right superior temporal sulcus than the left. Thus, such an approach, included in a longitudinal follow-up, may provide early indicators on the structural basis of cortical functional specialization and abnormalities induced by genetic and environmental factors.

Effect of CO2 laser conization of the uterine cervix on pathologic interpretation of cervical intraepithelial neoplasia.

The CO2 laser has become a valuable tool for the treatment of lower genital tract neoplasia. The records of 52 women who underwent CO2 laser cervical conization were analyzed retrospectively to evaluate the effect of tissue thermal damage on histopathologic interpretation. Lesion evaluability, defined by the ability to diagnose neoplasia accurately in the specimen, was satisfactory in only 26 cases; in the other 26, thermal damage was severe enough to preclude accurate diagnosis. A postoperative diagnosis of cervical intraepithelial neoplasia III was made in 17 instances, and microinvasion was suspected but unverifiable in two of these. Two patients had frankly invasive cancer, but vascular space involvement in one could not be evaluated accurately because of thermal damage. Tissue thermal damage sufficient to interfere with accurate histologic evaluation was noted in the majority of laser conization specimens. The value of a conization is both diagnostic and therapeutic. The potential impact of a diagnosis compromised by thermal damage is serious.

Management of regional lymph nodes and their prognostic influence in vulvar cancer.

One hundred thirteen patients with invasive carcinoma of the vulva underwent radical vulvectomy and bilateral inguinal-femoral lymphadenectomy between 1957 and 1978. Eighteen had unilateral pelvic lymphadenectomy. Thirty-one patients (27.4%) had positive lymph nodes. The corrected actuarial five-year survival for patients with negative nodes was 96%, whereas it was 94% for patients with one positive node, 80% for those with two positive nodes, and 12% for those with three or more positive nodes. All patients with positive pelvic nodes or pelvic recurrence had three or more positive unilateral groin nodes, and all had palpably suspicious groin nodes preoperatively. Groin and systemic recurrences occurred in 2.9 and 3.8%, respectively, of patients with fewer than three positive unilateral inguinal-femoral nodes, as compared to 33 and 66%, respectively, of patients with three or more positive nodes. These data do not support routine pelvic lymphadenectomy in patients who have no clinically suspicious groin nodes and fewer than three positive nodes on histologic examination.

Levator ani transposition for anal incompetence secondary to sphincter damage.

An operative procedure is described in which the levator ani muscles are used to correct anal incompetence secondary to sphincter damage. The relevant pelvic anatomy and operative procedure are described in detail. Four patients in whom sphincter damage occurred during surgery for posterior vulvar carcinoma underwent the procedure; in 3, good sphincter function was attained. Morbidity was minimal. The transposition of the levator ani muscle to replace partially obliterated anal sphincter muscles is a suitable procedure for patients who have insufficient sphincter tissue for simpler repairs.

Radical vulvectomy and bilateral inguinal lymphadenectomy through separate groin incisions.

One hundred patients underwent radical vulvectomy and bilateral inguinal lymphadenectomy using separate groin incisions. Forty-nine had stage I disease, 37 stage II, and 14 stage III. Corrected actuarial 5-year survival for each stage was 97.4, 86, and 49.2%, respectively. Inguinal lymph nodes were positive in 25% of cases: 10.2% of stage I, 27% of stage II, and 71.4% of stage III cases. Major complications occurred in 21 patients, including major groin breakdown in 14. Thirty patients experienced no acute postoperative morbidity. The mean postoperative hospital stay was 19 days, and mean operative blood loss was 620 ml. No patients developed isolated metastases in either the groin or the inguinal skin bridge, but 2 stage III patients developed simultaneous metastases in the skin bridge and elsewhere. For appropriately selected patients, separate groin incisions for inguinal lymphadenectomy appear to result in lower morbidity than traditional methods, without compromising survival.

Individualization of treatment for stage I squamous cell vulvar carcinoma.

Of 177 cases of invasive squamous cell vulvar cancer seen at the University of California at Los Angeles and the City of Hope National Medical Center from 1957 to 1980, 84 (47.5%) had stage I disease. Seventy-seven patients with stage I disease (91.7%) had stromal invasion of 5 mm or less. Correlation between lymph node status and depth of invasion was as follows: 1 mm or less, none of 34 (0%); 1.1 to 2 mm, two of 19 (10.5%); 2.1 to 3 mm, two of 17 (11.8%); 3 to 5 mm, one of seven (14.3%); more than 5 mm, three of seven (42.9%). Fifty-six patients had radical vulvectomy for the primary lesion, and 28 had more conservative excision, but the incidence of local invasive recurrence (4%) was the same in each group. None of 58 patients treated with inguinal-femoral lymphadenectomy developed a groin recurrence, but three of 26 patients (11.5%) who had omission or modification of inguinal-femoral lymphadenectomy died with groin recurrence within 12 months. These data suggest that although some modification of the standard radical vulvectomy is appropriate for the primary lesion in patients with stage I disease, patients with greater than 1 mm of stromal invasion require at least an ipsilateral inguinal-femoral lymphadenectomy.

Adenocarcinoma of the uterine cervix: histologic variables associated with lymph node metastasis and survival.

One hundred and two patients were treated for primary adenocarcinoma of the uterine cervix over a ten-year period from 1973 to 1982. Of these, 51 patients underwent initial surgical management that included a pelvic and para-aortic lymphadenectomy with a radical hysterectomy or a surgical staging operation. Clinical lesion size, grade, and depth of stromal invasion were correlated with lymph node metastasis and survival. The incidence of positive lymph nodes was 14.6% for stage I and 40.0% for stage II. Positive lymph nodes were documented in none of 15 patients with lesions smaller than 2 cm, 16.7% (five of 30) with 2 to 4 cm, and 82.3% (five of six) with larger than 4 cm; 5.3% of grade 1 tumors, 11.1% of grade 2, and 50.0% of grade 3. There were no lymph node metastases (zero of six) in patients with a tumor that had a depth invasion of less than 2 mm, whereas positive nodes were found in 11.1% (two of 18) patients with 2 to 5 mm of invasion, 28.6% (two of seven) with 5 to 10 mm, and 57.1% (four of seven) with greater than 10 mm of invasion. Five-year survival was 82.9% for stage I and 42.9% for stage II patients; 91.7% with negative lymph nodes, and 10% with positive nodes (P less than .0001). The size of the primary tumor (P less than .0001), tumor grade (P less than .05), and depth of invasion (P less than .05) correlated with patient survival.(ABSTRACT TRUNCATED AT 250 WORDS)

Primary carcinoma of the Bartholin gland: a report of 14 cases and review of the literature.

Fourteen cases of primary carcinoma of the Bartholin gland were treated between 1955 and 1980. Follow-up information was available on all patients. Ten patients have survived free of disease for 5 or more years. Three patients with positive inguinal lymph nodes have survived 5 years. Histological patterns and lymph node involvement are analyzed. The authors' data and a review of the literature support the concept that radical vulvectomy with bilateral inguinal-femoral lymphadenectomy is required for all histologic types of Bartholin gland carcinoma. Routine pelvic lymph node dissection is not necessary when the inguinal-femoral nodes are negative for metastases.

Nd: YAG laser therapy of rectosigmoid bleeding due to radiation injury.

The Nd:YAG laser was used to treat a patient bleeding from the rectosigmoid as a result of radiation injury related to therapy for cervical carcinoma. Successful laser therapy was performed after a diverting colostomy failed to control persistent bleeding. Further surgical procedures were not required. Characteristics of Nd:YAG laser as compared with those of the carbon dioxide and argon lasers are considered.

[Erythropoietin and neuroprotection]. / Erythropoïétine et neuroprotection.

Erythropoietin (Epo) has long been recognised for its role in the control of erythropoiesis and therefore in the treatment of anemia including anemia of prematurity. The erythropoietin receptor (Epo-R) though is expressed in many other organs including the CNS. This review focuses on the role of erythropoietin during the development of the CNS and its potential role as a neuroprotective agent. Epo-R is expressed in many different cellules of the CNS during development including neural progenitor cells, neurons, astrocytes and oligodendrocytes. In the event of hypoxia CNS cells respond with increase of erythropoietin release with subsequent stimulation of neurogenesis through Epo-R on neural progenitor cells. In an Epo-R knock-out model therefore cerebral development is severely impaired. In models of hypoxia-ischemia exogenous Epo has been shown to reduce lesion size and improve structural and functional recovery. Human studies are emerging using Epo as a neuroprotective agent both for the term infant with hypoxia-ischemia as well as for the extremely preterm infant.

Neuroendocrine features in poorly differentiated and undifferentiated carcinomas of the cervix.

Neuroendocrine or argyrophil cell carcinoma of the cervix has recently been accepted as a distinct clinical-pathological entity. The histologic pattern of these carcinomas is usually poorly differentiated or undifferentiated. Twenty patients with a histologic diagnosis of small cell carcinoma, undifferentiated carcinoma, poorly differentiated adenocarcinoma, or poorly differentiated, adenosquamous carcinoma of the cervix were evaluated for neuroendocrine features. The results of studies to detect neurosecretory granules were positive in seven of the 20 cases. Not only small cell carcinomas, but also tumors classified as undifferentiated carcinoma and poorly differentiated, adenosquamous carcinoma contained cytoplasmic granules consistent with neuroendocrine carcinoma of the cervix. The prognosis for survival appears poorer for patients having tumors with neurosecretory granules after controlling for stage and histologic grade of the neoplasm.

Does hysteroscopy improve upon the sensitivity of dilatation and curettage in the diagnosis of endometrial hyperplasia or carcinoma?

OBJECTIVE: The objective of this study was to determine whether hysteroscopy improved upon the diagnostic sensitivity of dilatation and curettage (D+C) in the detection of endometrial hyperplasia and carcinoma. METHODS: A retrospective chart review was conducted of all patients undergoing hysteroscopy/D+C for abnormal uterine bleeding between 1991 and 1995. Hysteroscopic impressions and D+C diagnoses were compared. RESULTS: Three hundred seventy-three patients were included in the study. Of the 61 patients with D+C demonstrating hyperplasia, the hysteroscopic impression was hyperplasia in 32 (52%). Of the 10 patients with D+C demonstrating carcinoma, the hysteroscopic impression was hyperplasia in 8 (80%) and carcinoma in 2 (20%). Two additional cases of carcinoma were diagnosed within 6 months of hysteroscopy/D+C, and both had been missed on both hysteroscopy and D+C. Of 204 patients with a normal hysteroscopic impression, 23 (11%) had hyperplasia on D+C. CONCLUSIONS: Hysteroscopy did not improve upon the sensitivity of D+C in the detection of endometrial hyperplasia or carcinoma.

Splenectomy and surgical cytoreduction for ovarian cancer.

OBJECTIVE: The aim of this study was to evaluate the role of splenectomy, as a surrogate marker for aggressive tumor cytoreduction in ovarian cancer, and its impact on patient morbidity and survival. METHODS: A retrospective cohort study of 35 patients who underwent splenectomy for ovarian cancer cytoreduction between August 1986 and May 1998 was performed. Data abstracted from the medical record included patient demographics, preoperative imaging, surgical procedures, tumor distribution, postoperative complications, chemotherapy treatment, and follow-up information. RESULTS: Splenectomy was performed in 13 patients at the time of primary cytoreduction and in 22 patients at the time of secondary cytoreduction. Preoperative diagnosis of splenic involvement was frequently made prior to secondary surgery, 77.3% compared to 15.4% of primary cases. In addition, parenchymal splenic involvement was more commonly observed at recurrence, 59.1% vs 23.1% at initial presentation. Disease distribution in secondary cytoreduction cases tended to be more focal, macronodular, and have no ascites. Cytoreduction to less than 1 cm disease was achieved in 100% of primary patients and 86% of secondary patients. Major morbidity (pneumonia, PE, sepsis, pancreatitis, MI) occurred in 23.1% of primary patients and 28.6% of secondary patients. Combining splenectomy with other cytoreductive procedures may make splenectomy itself seem more morbid. With a 17-month median follow-up, median progression-free interval was 24 months in primary patients and 14 months in secondary patients. Among secondary patients, median survival time after splenectomy and cytoreduction was 41 months. CONCLUSIONS: Splenectomy at the time of primary and secondary cytoreduction for ovarian cancer can be performed with acceptable morbidity. Secondary cytoreduction patients may be selected preoperatively by their progression-free interval, prior degree of cytoreduction, and macronodular tumor involvement on imaging studies. Identification of splenic involvement allows for appropriate counseling and preoperative preparation.

The influence of tumor grade, distribution, and extent of carcinomatosis in minimal residual stage III epithelial ovarian cancer after optimal primary cytoreductive surgery.

The purpose of this study was to determine the influence of tumor grade, distribution, and extent of carcinomatosis in minimal residual epithelial ovarian cancer after primary optimal cytoreductive surgery. Between 1978 and 1990, 112 patients with stage III epithelial ovarian cancer underwent primary cytoreductive surgery and had minimal residual disease, i.e., < 5 mm maximum diameter of residual tumor nodules. Seventy-eight patients (70%) had operative reports that contained sufficient detail to be included in this study. We retrospectively reviewed histopathological reports to determine tumor grade, operative and clinical notes to determine one predominant distribution pattern of residual metastases (pelvic/omental, diaphragmatic, or intestinal/mesenteric), and the approximate extent of residual disease (no gross disease, scattered nodules, or extensive carcinomatosis). Standard actuarial survival analysis was performed, and the log-rank chi 2 was used. At the mean follow-up time of 24.4 months, survival was 65% for grade 2 or 3 disease versus 93% for grade 1 (log-rank P < 0.01). Survival was 66% for residual disease in the intestines/mesentery versus 70 and 81% for residual disease in the diaphragm and pelvis/omentum, respectively (log-rank P < 0.03). Survival was 48% for residual extensive carcinomatosis versus 76 and 93% for minimal residual nodules and no gross residual, respectively (log-rank P < 0.001). In conclusion, in women who have minimal residual ovarian cancer after primary cytoreductive surgery, tumor grade and the distribution and extent of carcinomatosis can independently affect survival. The shortest survival correlated with high-grade tumor and extensive carcinomatosis predominantly involving the intestines and mesentery.

Development of endometrial cancer in women on estrogen and progestin hormone replacement therapy.

The presenting symptoms, hormonal regimens, treatment modalities, tumor pathology, and follow-up of 25 women developing endometrial cancer while receiving postmenopausal estrogen and progestin therapy were investigated retrospectively. Patients were interviewed and hormone therapies were confirmed through medical records. Pathology specimens were reviewed. Patients received conjugated estrogens (n = 20) or another estrogen (n = 5). For those on conjugated estrogens, the mean daily dose was 0.68 mg, monthly duration was 24.9 days, and monthly dose was 17.0 mg. Women also received medroxyprogesterone acetate (n = 23) or norethindrone acetate (n = 2). The most common regimen was sequential medroxyprogesterone acetate, at a mean daily dose of 7.5 mg, monthly duration of 9.3 days, and monthly dose of 68 mg (mean duration = 5.7 years). Most tumors were low stage and grade, with few demonstrating grade 3 disease (n = 2) or greater than 50% myometrial invasion (n = 2). Twenty-three (92%) had disease limited to the uterus, while two had stage IIIA disease. All are alive and disease-free after a median follow-up of 26 months. Estrogen and progestin therapy does not prevent endometrial cancer in all patients. Women who developed this tumor on sequential therapy in general received less than the recommended guidelines for daily dosage and monthly duration of progestin. Most patients had early-stage and low-grade disease. Continued vigilance in the care of women on hormone replacement therapy is necessary even when combination therapy is prescribed.