Nicola Ragni

Bowel endometriosis: Presentation, diagnosis, and treatment

Bowel endometriosis opens a new frontier for the gynecologist, as it forces the understanding of a new anatomy, a new physiology, and a new pathology. Although some women with bowel endometriosis may be asymptomatic, the majority of them develop a variety of gastrointestinal complains. No clear guideline exists for the evaluation of patients with suspected bowel endometriosis. Given the fact that, besides rectal nodules, bowel endometriosis can not be diagnosed by physical examination, imaging techniques should be used. Several techniques have been proposed for the diagnosis of bowel endometriosis including double-contrast barium enema, transvaginal ultrasonography, rectal endoscopic ultrasonography, magnetic resonance imaging, and multislice computed tomography enteroclysis. Medical management of bowel endometriosis is currently speculative; expectant management should be carefully balanced with the severity of symptoms and the feasibility of prolonged follow-up. Several studies demonstrated an improvement in quality of life after extensive surgical excision of the disease. Bowel endometriotic nodules can be removed by various techniques: mucosal skinning, nodulectomy, full thickness disc resection, and segmental resection. Although the indications for colorectal resection are controversial, recent data suggest that aggressive surgery improves symptoms and quality of life. Target Audience: Obstetricians & Gynecologists, Family Physicians Learning Objectives: After completion of this article, the reader should be able to describe the varied appearance of bowel endometriosis, recall that it is difficult to diagnose preoperatively, and explain that surgical treatment offers the best treatment in symptomatic patients through a variety of surgical techniques which is best accomplished with a team approach.

Crosstalk between decidual NK and CD14+ myelomonocytic cells results in induction of Tregs and immunosuppression

Regulatory T cells (Tregs) are thought to play a major role in pregnancy by inhibiting the maternal immune system and preventing fetal rejection. In decidual tissues, NK cells (dNK) reside in close contact with particular myelomonocytic CD14+ (dCD14+) cells. Here we show that the interaction between dNK and dCD14+ cells results in induction of Tregs. The interaction is mediated by soluble factors as shown by transwell experiments, and the prominent role of IFN-γ is revealed by the effect of a neutralizing monoclonal antibody. Following interaction with dNK cells, dCD14+ cells express indoleamine 2,3-dioxygenase (IDO), which, in turn, induces Tregs. Notably, unlike peripheral blood NK (pNK) cells, dNK cells are resistant to inhibition by the IDO metabolite L-kynurenine. “Conditioned” dCD14+ cells also may induce Tregs through transforming growth factor-β (TGF-β) production or CTLA-4–mediated interactions, as indicated by the effect of specific neutralizing Abs. Remarkably, only the interaction between dNK and dCD14+ cells results in Treg induction, whereas other coculture combinations involving either NK or CD14+ cells isolated from peripheral blood are ineffective. Our study provides interesting clues to understanding how the crosstalk between decidual NK and CD14+ cells may initiate a process that leads to Treg induction and immunosuppression. Along this line, it is conceivable that an impaired function of these cells may result in pregnancy failure.

HER2/neu oncoprotein overexpression in epithelial ovarian cancer : Evaluation of its prevalence and prognostic significance clinical study

Introduction: The HER2/neu proto-oncogene encodes a transmembrane receptor protein involved in the development and progression of the majority of cancers. Prior studies have shown that HER2/neu oncogene is overexpressed in approximately 15–30% of ovarian carcinomas. However findings regarding the overexpression and prognosis are still conflicting. Methods: Our retrospective study was performed on 194 ovarian carcinoma tissues obtained at the time of first surgery. The staining procedure for HER2/neu overexpression was performed using a polyclonal antibody. Results: HER2/neu overexpression was found in 53 out of 194 (27.3%) investigated cases of which 26 (13.4%) carcinomas were weakly positive (score 1+) and 27 (13.9%) moderately (score 2+) to intensely positive (score 3+). No significant relationship was found between HER2/neu score and main clinical and pathological features. Significant difference in overall survival was evident between negative women (0/1+) and positive women (2+/3+): 48 and 29 months, respectively (p = 0.04). In multivariate analysis HER2/neu overexpression appeared to be the only variable significantly correlated with progression and death. CA125 normalization at 3 and 6 months appeared a strong predictor of progression and survival. Conclusion: In this study HER2/neu overexpression was associated with an increased risk of progression and death, especially among women with FIGO Stage I and II ovarian carcinoma.

Multislice CT enteroclysis in the diagnosis of bowel endometriosis

This prospective study aims to evaluate the efficacy of multislice computed tomography combined with colon distension by water enteroclysis (MSCTe) in determining the presence and depth of bowel endometriotic lesions. Ninety-eight women with symptoms suggestive of colorectal endometriosis underwent MSCTe; locations, number of nodule/s, size of the nodule/s and depth of bowel wall infiltration were determined. Independently from the findings of MSCTe, all women underwent laparoscopy. MSCTe findings were compared with surgical and histological results. Abnormal findings suggestive of bowel endometriotic nodules were detected by MSCTe in 75 of the 76 patients with bowel endometriosis. MSCTe identified 110 (94.8%) of the 116 bowel endometriotic nodules removed at surgery; 6 nodules missed at MSCTe were located on the rectum. MSCTe correctly determined the degree of infiltration of the bowel wall in all of the 34 serosal bowel nodules identified at MSCTe. In six nodules reaching the submucosa, the depth of infiltration was underestimated by MSCTe. MSCTe had a sensitivity of 98.7%, a specificity of 100%, a positive predictive value of 100% and a negative predictive value of 95.7% in identifying women with bowel endometriosis. MSCTe is effective in determining the presence and depth of bowel endometriotic lesions.

Prospective study of mother-to-infant transmission of hepatitis C virus: a 10-year survey (1990-2000)

Background. The purpose of this study was to determine the rate of vertical transmission of hepatitis C virus (HCV). We also aimed to analyze the time of clearance of maternal antibodies in the serum of non‐infected babies.

Inflammatory bowel disease: management issues during pregnancy.

IntroductionInflammatory bowel disease often affects women during their reproductive years, causing management concerns for obstetricians caring for these patients during pregnancy.TreatmentApart from methotrexate, most drugs used regularly to treat ulcerative colitis and Crohns disease can safely be used by pregnant women. No causal relationship has been established between exposure to sulfasalazine or other 5-aminosalicylic acid drugs and the development of congenital malformations and these drugs may be used with relative safety during pregnancy and lactation. Current evidence indicates that maternal use of azathioprine and mercaptopurine is not associated with an increased risk of congenital malformations, though impaired foetal immunity, intrauterine growth retardation and prematurity are occasionally observed. Cyclosporin is not teratogenic, but may be associated with growth retardation and prematurity.ConclusionsPregnancy should be avoided in women treated with methotrexate because of its known abortifacient effects and risk of causing typical malformations. There is no actual evidence of adverse effect in pregnant women receiving Infliximab but the amount of clinical information is small. The treatment with metronidazole or ciprofloxacin for short durations appear to be safe, but there is no data about the effects of increased length of treatment as required in Crohns disease remains unknown. Control of disease activity before conception and during pregnancy is critical to optimise both maternal and foetal health. A multidisciplined approach involving both obstetrician and gastroenterologist and education about pregnancy are essential components of the treatment of any young women with IBD.

Fertility after bowel resection for endometriosis.

OBJECTIVE To determine the pregnancy rate after bowel resection for rectosigmoid endometriosis. DESIGN Prospective cohort study. SETTING University hospital. PATIENT(S) Forty-six symptomatic women with bowel endometriosis requiring colorectal resection. INTERVENTION(S) Bowel resection by either laparoscopy or laparotomy. MAIN OUTCOME MEASURE(S) Pregnancy rate after surgery. RESULT(S) The pregnancy rate was higher in women who underwent bowel resection by laparoscopy (57.6%) than in those who underwent laparotomy (23.1%). No significant difference was observed in pregnancy rate and mode of conception between women with different fertility status before bowel resection. Women who conceived were significantly younger than those who did not conceive; only 26.7% of women aged > or =35 years conceived after bowel resection. Uterine adenomyosis was more frequently present in women who did not conceive than in those who conceived. Infertile women who conceived had a shorter length of infertility before surgery than those who did not conceive. CONCLUSION(S) Laparoscopic colorectal resection is less likely to impact negatively on fertility than the laparotomy approach. Previous laparotomies, age > or =35 years, uterine adenomyosis, and longer duration of infertility before surgery are associated with decreased pregnancy rate.

Does transvaginal ultrasonography combined with water-contrast in the rectum aid in the diagnosis of rectovaginal endometriosis infiltrating the bowel?

BACKGROUND The aim of this study was to determine whether adding water-contrast in the rectum during transvaginal ultrasonography (RWC-TVS) improves the diagnosis of rectal infiltration in women with rectovaginal endometriosis. METHODS This prospective study included 90 women, with suspect rectovaginal endometriosis, who underwent operative laparoscopy. TVS and RWC-TVS were independently performed by different investigators. RWC-TVS was performed by injecting saline solution into the rectal lumen under ultrasonographic control through a 6-mm catheter. Presence of rectovaginal nodules, presence and degree of rectal infiltration, and the largest diameter of the bowel nodules were evaluated. Ultrasonographic results were compared to surgical and histological findings. RESULTS Although RWC-TVS had higher accuracy than TVS in diagnosing rectovaginal endometriosis, the difference between the two techniques was not statistically significant. RWC-TVS was significantly more accurate than TVS in determining the presence of endometriotic infiltration reaching at least the muscular layer of the rectal wall. The sensitivity of RWC-TVS in identifying rectal lesions was 97%, the specificity 100%, the positive predictive value 100% and the negative predictive value 91.3%. RWC-TVS caused a higher intensity of pain than TVS. CONCLUSIONS RWC-TVS determines the presence of rectovaginal nodules infiltrating the rectal muscularis propria more accurately than TVS; RWC-TVS could be used when TVS cannot exclude the presence of rectal infiltration.

Norethisterone acetate in the treatment of colorectal endometriosis: a pilot study

BACKGROUND This pilot study evaluates the efficacy of norethisterone acetate in treating pain and gastrointestinal symptoms of women with colorectal endometriosis. METHODS This prospective study included 40 women with colorectal endometriosis, who had pain and gastrointestinal symptoms. Patients received norethisterone acetate (2.5 mg/day) for 12 months; in case of breakthrough bleeding, the dose of norethisterone acetate was increased by 2.5 mg/day. The degree of patient satisfaction with treatment (primary end-point) and the changes in symptoms (secondary end-point) were evaluated. Side effects of treatment were recorded. RESULTS Norethisterone acetate determined a significant improvement in the intensity of chronic pelvic pain, deep dyspareunia, dyschezia. Treatment determined the disappearance of symptoms related to the menstrual cycle (dysmenorrhea, constipation during the menstrual cycle, diarrhoea during the menstrual cycle and cyclical rectal bleeding). The severity of diarrhoea, intestinal cramping and passage of mucus significantly improved during treatment. On the contrary, the administration of norethisterone acetate did not determine a significant effect on constipation, abdominal bloating and feeling of incomplete evacuation after bowel movements. At the completion of treatment, 57% of the patients with diarrhoea or diarrhoea during the menstrual cycle continued the treatment with norethisterone acetate compared with 17% of the patients with constipation or constipation during the menstrual cycle. CONCLUSIONS In some patients with bowel endometriosis, the administration of norethisterone acetate may determine a relief of pain and gastrointestinal symptoms. This therapy has greater benefits in patients with gastrointestinal symptoms related to the menstrual cycle, diarrhoea and intestinal cramping.

Letrozole and desogestrel‐only contraceptive pill for the treatment of stage IV endometriosis

Background:  It has recently been suggested that aromatase inhibitors may effectively reduce pain symptoms related to the presence of endometriosis both in postmenopausal women and in subjects of reproductive age.