Diethylstilbestrol exposure during pregnancy with primary clear cell carcinoma of the cervix in an 8-year-old granddaughter: a multigenerational effect of endocrine disruptors?

To date, vaginal/cervical clear cell adenocarcinoma (CCAC) has not been reported in the granddaughters of women treated with diethylstilbestrol (DES) during pregnancy. We present an 8-year-old girl with a history of severe vaginal bleeding who was diagnosed with cervical CCAC. She underwent fertility-sparing surgery and radiotherapy. No sign of recurrence was detected throughout a 10-year follow-up. Her grandmother had received DES therapy during pregnancy with the patient's mother. Although no direct causal link is demonstrated, this case raises for the first time, the hypothesis of multigenerational effects of DES in girls and strongly suggests the need to follow the granddaughters of DES-treated women.

Treatment failure following excision therapy of CIN: the impact of direct colposcopic vision during procedure.

PURPOSE: To assess whether the use of direct colposcopic vision during excision therapy of cervical intraepithelial neoplasia (CIN) has an impact on the risk of treatment failure. METHODS: Data from 285 patients who had had excision therapy with proven CIN at specimen histological analysis were reviewed. Primary endpoint was the occurrence of post-treatment failure defined by the histological diagnosis of CIN 2-3 during follow-up. Data were analysed according to the use of colposcopy at the time of initial therapy of CIN. RESULTS: The use of direct colposcopic vision (DCV) resulted in a significant reduction in the mean height (p = 0.008) and diameter (p < 0.001) of the excised specimen. Patients' median follow-up was 28.4 (±1.3) months. A total of 43 (15.2 %) patients were diagnosed with treatment failure. Compared to excisions performed without any use of colposcopy, DCV was not found to have any significant impact on the risk of treatment failure (HR: 0.58; 95 % CI 0.16-2.13, p = 0.412), neither when compared to excisions performed immediately after colposcopy (HR: 0.91; 95 % CI 0.47-1.79; p = 0.794). The only factors found to have a significant impact on the risk of treatment failure was the identification of clear margins (HR: 0.36; 95 %CI 0.19-0.69; p = 0.002) and the diameter of the surgical specimen (HR: 0.94; 95 %CI 0.89-0.99; p = 0.040). CONCLUSIONS: Although the use of DCV during excision therapy of CIN was associated with a significant reduction in the dimensions of the excised cervical specimen, it did not result in a significant change in the risk of treatment failure.

Benefits of Direct Colposcopic Vision for Optimal LLETZ Procedure: A Prospective Multicenter Study.

OBJECTIVE: The aim of the study was to assess whether direct colposcopic vision (DCV) of the cervix during large loop excision of the transformation zone (LLETZ) is associated with a decrease in the volume and dimensions of specimens or affects margin status at histology. MATERIALS AND METHODS: A prospective multicenter observational study of 216 women who underwent LLETZ for grades 2 and 3 cervical intraepithelial neoplasia was conducted. The volume and dimensions (circumference, length, and thickness) of the surgical specimens were measured before fixation. Data were compared according to the use of colposcopy during LLETZ. The following 3 groups were considered: LLETZ performed without colposcopy (n = 91), LLETZ performed immediately after colposcopy (n = 51), and LLETZ performed under DCV (n = 74). RESULTS: Patient characteristics were comparable with regard to age, parity, history of excision, indication of the procedure, and the size of the cervix. We found a significant decrease in all dimensions of the specimens obtained under DCV (p < .001). Margin status was not affected. After adjusting for confounders, the mean volumes were significantly lower in the DCV group (adjusted mean difference = -0.66 mL; 95% CI = -1.17 to -0.14). The probability that negative margins would be achieved together with the attainment of a volume less than 5 mL and a thickness less than 10 mm was the highest in the DCV group (adjusted OR = 2.80; 95% CI = 1.13 to 6.90). CONCLUSIONS: Direct colposcopic vision is associated with a significant decrease in the volume and in all dimensions of LLETZ specimens with no compromise in the margin status.

Relationship between HPV 16, 18, 31, 33, 45 DNA detection and quantitation and E6/E7 mRNA detection among a series of cervical specimens with various degrees of histological lesions.

Better understanding of the correlation between high-risk HPV DNA testing, viral load quantitation, and E6/E7 mRNA detection is required. The aim of this study was to assess the relationship between these markers and the severity of cervical lesions. One-hundred and fifty one directed cervical specimens were analysed (normal, cervical intraepithelial neoplasia, and cancer). HPV types 16, 18, 31, 33, and 45 DNA detection and quantititation and E6/E7 mRNA detection were performed. DNA was detected in 87 (57.6%) samples and increased from 0% (normal) to 93.9% (cancer). E6/E7 mRNA was detected in 65 (43%) samples and increased with the severity of the lesions from 0% (normal) to 78.8% (26/33) (cancers) (P < 0.001). HPV DNA and E6/E7 mRNA detection were compared in the 141 samples harbouring HPV16, 18, 31, 33, or 45 infection: 45.4% (64/141) of specimens were DNA-/mRNA-, 46% (65/141) were DNA + /mRNA+ and 8.5% (12/141) were DNA + /mRNA-. The proportion of DNA + /mRNA+ specimens increased with the severity of the lesions (P < 0.001). All normal cervix specimens were DNA-/mRNA-. Among grade 2 cervical intraepithelial neoplasia, prevalence of DNA was higher than that of mRNA: 41.6% (5/12) versus 25% (3/12), whereas it was 79.3% (46/58) versus 62% (36/58) among grade 3 cervical intraepithelial neoplasia. Full concordance was observed in cancers as all the 26 DNA+ specimens were mRNA +. Median overall HPV load was higher in DNA + /mRNA+ than in DNA + /mRNA- specimens (1.41 × 10(6) vs. 9.1 × 10(2) copies per million cells, P < 0.001). Both E6/E7 mRNA detection and concordant DNA + /mRNA+ detection increases with the severity of the lesions and with the HPV DNA load.

Spontaneous resolution of severe, symptomatic mesocolic panniculitis: a case report.

BACKGROUND: Mesenteric panniculitis is a rare chronic fibrosing inflammatory disease that typically affects the adipose tissue and mesentery of the small intestine but may also affect the mesosigmoid and the mesocolon. The pathology of this disease remains unclear despite association with some malignancies or inflammatory disorders. We report a case of mesocolic panniculitis and a literature review of its clinical presentation, imaging findings, associated conditions and treatment options. CASE PRESENTATION: A 64 year-old Caucasian man was admitted to the gastroenterology department for severe weakness, left lower quadrant abdominal pain, weight loss and diarrhoea. Physical examination revealed a palpable firm mass occupying the entire left part of the abdomen. Abdominal CT-scan showed fatty infiltration of the mesosigmoid and left mesocolic fat which was strongly suggestive of panniculitis. Laparoscopic surgery revealed an inflamed and edematous mesocolon and mesosigmoid; the sigmoid mucosa appeared petechial which was suggestive of venous ischemia. Histological examination of surgical biopsies revealed mesocolic panniculitis. Despite exhaustive investigation, no associated conditions were found and the cause was classified as idiopathic. Surprisingly, the patient clinically improved without therapeutic intervention other than supportive care. CONCLUSION: Although mesenteric panniculitis is most often a radiographic diagnosis without clinical symptomatology, it can also present with significant general status alteration. We report a case of mesocolic panniculitis complicated by development of an inflammatory mass associated with ischemic colitis. Mesenteric panniculitis is a difficult diagnosis to make which typically requires histologic confirmation. The overall prognosis is good with supportive treatment.

Validation of an immunohistochemical signature predictive of 8-year outcome for patients with breast carcinoma.

We recently reported that standardized quantitative immunohistochemical (IHC) assays allowed prediction of an adverse outcome among 572 node negative (N-) patients with breast carcinoma (BrCa). To further validate our prior findings, we repeated the IHC stains including a second series of BrCa diagnosed at Yale University. Tissue microarrays (TMAs) of two cohorts of patients with BrCa (418 Marseille University and 303 Yale University) were respectively investigated for IHC expression of 15 markers (HIF-1α, PI3K, pAKT, pmTOR, moesin, P21, 4(E) BP-1, P27, Ker5-6, pMAPKAPK-2, SHARP2, claudin-1, ALDH, AF6 and CD24). Quantitative measurements of immunoprecipitates densitometry assessed with an image analyzer were correlated with 8-year patients' outcome and compared in the two cohorts. The best predictive signature consisted of a combination of five markers that included HIF-1α, PI3K, claudin-1, AF6 and pAKT in N- BrCa. This combination permitted an accurate prediction of outcome in 92.34% (386/418) of N- patients in the first set (Marseille) and 89.8% (158/176) in the second set (Yale). The close results in both cohorts confirmed the validity of this original IHC signature predictive of prognosis in node negative BrCa. This validation suggests that in clinical practice, it would be possible with standardized kits (i) to identify patients with poor prognosis at diagnosis time, particularly in the N- BrCa subset, who would require more aggressive adjuvant therapy and (ii) to avoid useless expensive therapies and their side effects in N- patients with favorable prognosis.