Laparoscopic En Bloc Right Diaphragmatic Peritonectomy for Diaphragmatic Endometriosis According to the Sugarbaker Technique.

STUDY OBJECTIVE: To evaluate the feasibility of a novel laparoscopic procedure for complete eradication of diaphragmatic endometriosis (DE). DESIGN: A retrospective multicenter study (Canadian Task Force Classification II-2). SETTING: University tertiary referral centre. PATIENTS: A consecutive series of 9 women with DE. INTERVENTIONS: Laparoscopic en bloc eradication using Sugarbaker's peritonectomy technique with or without diaphragmatic resection for DE. All surgical procedures were performed by the same surgeon in 2 tertiary referral centers (Charitè University, Berlin, Germany, and Catholic University of the Sacred Heart, Foundation John Paul II, Campobasso, Italy). MEASUREMENTS AND MAIN RESULTS: Rate of conversion to laparotomy, perioperative outcomes, intra- and postoperative complications, and recurrence rate. The procedures were successfully performed in all patients laparoscopically without conversion to laparotomy. All patients also presented with multiple endometriotic lesions in the Morison pouch, and in 3 cases a deep infiltration of the right diaphragm was observed that required partial diaphragmatic resection. In 2 women, pulmonary nodules were also detected, and lung laparoscopic resection was attempted to eradicate the disease. A chest drain was placed in 7 women and was removed after a median time of 6 days (range, 4-10 days). No intra- or postoperative complications were recorded. To complete the diaphragmatic peritonectomy, the median operative time required was 180 minutes (range, 90-240 minutes). The median estimated blood loss was 100 mL (range, 50-300 mL), and the median hospital stay was 10 days (range, 5-17 days). After a median follow-up of 6 months, we observed symptomatic relief for all study patients without major surgery-related morbidity. In 1 woman, laparoscopic adhesiolysis was performed after 18 months from surgery without signs of recurrent endometriosis. CONCLUSION: Laparoscopic en bloc eradication of DE with Sugarbaker's peritonectomy is highly effective in the management of symptomatic DE, with no major intra-/postoperative complications and very favorable perioperative outcomes.

Ligneous cervicitis in a woman with plasminogen deficiency associated with an atypical form of microglandular hyperplasia: a case report and review of literature.

A 19-yr-old woman with previously diagnosed clear cell adenocarcinoma was referred to the Charité for further treatment. Biopsies were taken from the cervix, the endometrium, pseudomembranes in the peritoneum, and sentinel lymph nodes. The morphologic picture of pseudomembranes and inflammation together with the provided information about plasminogen deficiency of the patients led to the hypothesis of ligneous cervicitis. The previously taken biopsies of the adenocarcinoma were reevaluated and showed a clear cell lesion. Further immunohistochemical examination with antibodies against p16, Ki67, CEA, and p53 could not prove its malignant character. As a result we diagnosed an atypical form of microglandular hyperplasia in a patient with ligneous cervicitis. Ligneous cervicitis is a rare inflammatory condition that might affect all mucus membranes in patients with plasminogen deficiency. This case shows the importance of correlating pathologic and clinical findings in the diagnosis of ligneous cervicitis because of the rarity of the disease and the heterogeneity at presentation.

Detection of human papillomavirus type 18 E7 oncoprotein in cervical smears: a feasibility study.

Persistent infections by high-risk human papillomaviruses (HPVs) are the main etiological factor for cervical cancer, and expression of HPV E7 oncoproteins was suggested to be a potential marker for tumor progression. The objective of this study was to generate new reagents for the detection of the HPV18 E7 oncoprotein in cervical smears. Rabbit monoclonal antibodies against recombinant E7 protein of HPV type 18 (HPV18) were generated and characterized using Western blotting, epitope mapping, indirect immunofluorescence, and immunohistochemistry. One clone specifically recognizing HPV18 E7 was used for the development of a sandwich enzyme-linked immunosorbent assay (ELISA). The assay was validated using recombinant E7 proteins of various HPV types and lysates from E7-positive cervical carcinoma cells. A total of 14 HPV18 DNA-positive cervical swab specimens and 24 HPV DNA-negative-control specimens were used for the determination of E7 protein levels by the newly established sandwich ELISA. On the basis of the average absorbance values obtained from all 24 negative controls, a cutoff above which a clinical sample can be judged E7 positive was established. Significant E7 signals 6- to 30-fold over background were found in 7 out of 14 abnormal HPV18 DNA-positive cervical smear specimens. This feasibility study demonstrates for the first time that HPV18 E7 oncoprotein can be detected in cervical smears.

Combined Expression of HGFR with Her2/neu, EGFR, IGF1R, Mucin-1 and Integrin α2ß1 Is Associated with Aggressive Epithelial Ovarian Cancer.

Hepatocyte growth factor receptor (HGFR), also known as c-mesenchymal-epithelial transition factor (c-MET), plays a crucial role in the carcinogenesis of epithelial ovarian cancer (EOC). In contrast, the mechanisms contributing to aberrant expression of HGFR in EOC are not fully understood. In the present study, the expression of HGFR with its prognostic and predictive role was evaluated immunohistochemically in a cohort of 42 primary ovarian cancer patients. Furthermore, we analyzed the dual expression of HGFR and other druggable biomarkers. In the multivariate Cox regression analysis, high HGFR expression was identified as an independent prognostic factor for a shorter progression-free survival (PFS) (hazard ratio (HR) 2.99, 95% confidence interval (CI95%) 1.01-8.91, p = 0.049) and overall survival (OS) (HR 5.77, CI95% 1.56-21.34, p = 0.009). In addition, the combined expression of HGFR, human epidermal growth factor receptor 2 (Her2/neu), epithelial growth factor receptor (EGFR), insulin-like growth factor 1 (IGF1R), Mucin-1 and Integrin α2ß1 further significantly impaired PFS, platinum-free interval (PFI) and OS. Protein co-expression analyses were confirmed by transcriptomic data in a large, independent cohort of patients. In conclusion, new biomarker-directed treatment targets were identified to fight poor prognosis of primary EOC.

Integrin α2ß1 Represents a Prognostic and Predictive Biomarker in Primary Ovarian Cancer.

Currently, the same first-line chemotherapy is administered to almost all patients suffering from primary ovarian cancer. The high recurrence rate emphasizes the need for precise drug treatment in primary ovarian cancer. Being crucial in ovarian cancer progression and chemotherapeutic resistance, integrins became promising therapeutic targets. To evaluate its prognostic and predictive value, in the present study, the expression of integrin α2ß1 was analyzed immunohistochemically and correlated with the survival data and other therapy-relevant biomarkers. The significant correlation of a high α2ß1-expression with the estrogen receptor alpha (ERα; p = 0.035) and epithelial growth factor receptor (EGFR; p = 0.027) was observed. In addition, high α2ß1-expression was significantly associated with a low number of tumor-infiltrating immune cells (CD3 intratumoral, p = 0.017; CD3 stromal, p = 0.035; PD-1 intratumoral, p = 0.002; PD-1 stromal, p = 0.049) and the lack of PD-L1 expression (p = 0.005). In Kaplan-Meier survival analysis, patients with a high expression of integrin α2ß1 revealed a significant shorter progression-free survival (PFS, p = 0.035) and platinum-free interval (PFI, p = 0.034). In the multivariate Cox regression analysis, integrin α2ß1 was confirmed as an independent prognostic factor for both PFS (p = 0.021) and PFI (p = 0.020). Dual expression of integrin α2ß1 and the hepatocyte growth factor receptor (HGFR; PFS/PFI, p = 0.004) and CD44v6 (PFS, p = 0.000; PFI, p = 0.001; overall survival [OS], p = 0.025) impaired survival. Integrin α2ß1 was established as a prognostic and predictive marker in primary ovarian cancer with the potential to stratify patients for chemotherapy and immunotherapy, and to design new targeted treatment strategies.

Outpatient hysteroscopic emptying of a submucosal uterine cystic lesion.

BACKGROUND: Uterine cystic neoformations are rare, but they should always be investigated to differentiate a benign from a malignant pathology. Transvaginal ultrasonography, MRI, and blood tests are the main investigations for diagnosing these lesions, avoiding over- or undertreatment. Hysteroscopy might represent a helpful tool both for its diagnostic and therapeutic properties. METHODS: We report the hysteroscopic emptying of a cystic-degenerated leiomyoma with a 5-Fr flexible needle inserted through the operative channel of a 5-mm continuous-flow operative office hysteroscope in an outpatient setting. RESULTS: The cystic lesion was successfully emptied. The hystopathological result of the target biopsies performed on the cystic wall was cystic degeneration of a leiomyoma. CONCLUSION: This needle is normally used in gynecology to instill intrauterine local anesthesia under a hysteroscopic view. We adapted it to drain a fluid-filled lesion, identifying a further application of this instrument.

Reduced Sympathetic Innervation in Endometriosis is Associated to Semaphorin 3C and 3F Expression.

Endometriosis is a chronic inflammatory disease and one of the most common causes of pelvic pain. The mechanisms underlying pain emergence or chronic inflammation during endometriosis remain unknown. Several chronic inflammatory diseases including endometriosis show reduced amounts of noradrenergic nerve fibers. The source of the affected innervation is still unclear. Semaphorins represent potential elicitors, due to their known role as axonal guidance cues, and are suggested as nerve repellent factors in different chronic inflammatory diseases. Therefore, semaphorins might influence the progress of neuroinflammatory mechanisms during endometriosis. Here, we analyzed the noradrenergic innervation and the expression of the specific semaphorins and receptors possibly involved in the neuroimmunomodulation in endometriosis. Our studies revealed an affected innervation and a significant increase of semaphorins and their receptors in peritoneal endometriotic tissue. Thereby, the expression of the receptors was identified on the membrane of noradrenergic nerve fibers and vessels. Macrophages and activated fibroblasts were found in higher density levels and additionally express semaphorins in peritoneal endometriotic tissue. Inflammation leads to an increased release of immune cells, which secrete a variety of inflammatory factors capable of affecting innervation. Therefore, our data suggests that the chronic inflammatory condition in endometriosis might contribute to the increase of semaphorins, which could possibly affect the innervation in peritoneal endometriosis.

Ultramicro-trauma in the endometrial-myometrial junctional zone and pale cell migration in adenomyosis.

OBJECTIVE: To determine if ultrastructural tissue trauma occurs in the junctional zone in uteri in adenomyosis. DESIGN: A case-control experimental study. SETTING: Endometriosis research center. PATIENT(S): Twelve uteri with adenomyosis, and 9 uteri without adenomyosis, were gained during laparoscopy-assisted vaginal hysterectomy. INTERVENTION(S): Transmission electron microscopic study of the junctional zone, as well as immunohistochemical staining for epithelial cadherin, and van Gieson staining and immunofluorescence for CD45 and CD68. MAIN OUTCOME MEASURE(S): Analysis of the electron microscopy photos and the immunoreactive scores of the staining. RESULT(S): The inner myometrial muscle fibers were diversely arranged in adenomyosis; they were parallel to the basal endometrial glands in nonadenomyosis. Nuclear membrane infolding of the basal glandular epithelium and the disruption of the interface between basal endometrium and inner myometrium in adenomyosis (but not in nonadenomyosis) were evident. Intraepithelial pale cells were seen in the basal endometrial glands in both groups, but they lacked CD45 and CD68 expression. They were seen actively migrating into the stroma in adenomyosis only. CONCLUSION(S): The myofiber disarray in the inner myometrium, and the nuclear membrane irregularities in adenomyosis, are evidence for ultramicro-trauma in adenomyosis. The migrating nonleukocytic pale cells may be involved in pathogenesis of adenomyosis.