Submucous Fibroids, Fertility, and Possible Correlation to Pseudocapsule Thickness in Reproductive Surgery.

BACKGROUND AND OBJECTIVES: Fibroids are related to infertility. Fibroid pseudocapsule is a neurovascular bundle surrounding leiomyomas rich of neurofibers involved in myometrial biology. Authors evaluated, by a case-control study, the fibroid pseudocapsule (FP) thickness by ultrasound (US) and the histological measurements, according to uterine location of fibroids. METHODS: 137 consecutive patients undergoing hysterectomy for uterine myomas were enrolled and 200 myomas were evaluated. Before surgery, patients underwent an ultrasound (US) investigation to evaluate the number, the size, and the location of fibroids. After surgery, myoma-pseudocapsule-myometrium specimens were measured and evaluated by a single expert pathologist. Both US and histological data were collected and statistically analyzed. RESULTS: Our results confirm the relevant difference of FP thickness, particularly represented under the endometrium for submucous LMs. FPs near the endometrial cavity were considerably thicker than those of both intramural fibroids and subserous fibroids measured by US (P=0.0001) and histology (P=0.0001). A clear cut-off measurement at 2 mm (P=0.0001) was found between endometrial FPs and all other FPs for either US or histology measurements. CONCLUSION: The thickness of FP is considerably higher near the endometrial cavity when compared to those of both intramural and subserous LMs, suggesting a potential role either in fertility or in myometrial healing.

A Proteomic Analysis of Human Uterine Myoma.

Uterine leiomyoma is a benign smooth muscle tumor characterized by a high incidence in women of reproductive age. The aetiology of this tumor is still unknown but established risk factors include high levels of female hormones, family history, African ancestry, early age of menarche and obesity. Here, to identify proteomic features associated with this tumor type, we performed a liquid chromatography-mass spectrometry (LC-MS/MS) analysis of uterine myomas. The identified proteins were subjected to a gene ontology analysis to generate biological functions, molecular processes, and protein networks that were relevant to the uploaded dataset. Pathway-based analysis was an effective approach to investigate the molecular mechanisms underlying the disease and to create biological hypotheses about regulation of our proteins including the identification of upstream regulators and main protein nodes. Moreover, proteomic and in silico data were combined with immunohistochemistry and western blotting to identify a group of proteins representative of some selected pathways, with a dysregulated expression in myoma, pseudocapsule, and normal myometrium samples. Based on these results, we confirmed the over-expression of extracellular matrix components, and estrogen and progesterone receptors in uterine myomas, and proposed biological networks, canonical pathways and functions that may be relevant to the pathophysiology of this tumor.

A combined ultrasound and histologic approach for analysis of uterine fibroid pseudocapsule thickness.

Authors investigated 75 patients with uterine myomas, appraising whether fibroid pseudocapsule (FP) thickness varies depending on fibroid location, by a prospective cohort trial (level of evidence II-2) settled in University-affiliated Hospitals. Uteri were scanned via bidimensional and power Doppler ultrasound (US) to map the fibroids and record the FP thickness, prior to hysterectomy for symptomatic uterine fibroids. After hysterectomy, FP specimens were sampled and analyzed by pathologists. Ultrasound and histology data were matched. Pseudocapsule thickness of 108 fibroids was measured: subserosal fibroids (SSFs), intramural fibroids (IMFs), and fibroids near the endometrial cavity (FEC). The FEC's pseudocapsules were considerably thicker than those of IMF and SSF measured by US and histology (P = .001). A clear cutoff existed between FEC pseudocapsule thickness and all other pseudocapsules, with significant differences observed at 2 mm (P = .001). Similarity between histological and US measurements was observed only with IMF pseudocapsules, whereas FEC or SSF showed significant differences. The pseudocapsule of fibroids is considerably thicker near the endometrial cavity when compared to those of both IMFs and SSFs. Since fibroids closest to the endometrial cavity are the most involved in fertility and infertility and FP is considerably thicker near the endometrial cavity, it is possible to hypothesize an involvement of FP of fibroid near the endometrium since FP contains many neuropeptides and neurotransmitters that are physiologically active, even if these data may take on a broader meaning in a study on a larger number of patients.

The opioid neuropeptides in uterine fibroid pseudocapsules: a putative association with cervical integrity in human reproduction.

The myoma pseudocapsule (MP) is a fibro-vascular network rich of neurotransmitters, as a neurovascular bundle, surrounding fibroid and separating myoma from myometrium. We investigated the distribution of the opioid neuropeptides, as enkephalin (ENK) and oxytocin (OXT), in the nerve fibers within MP and their possible influence in human reproduction in 57 women. An histological and immunofluorescent staining of OXT and ENK was performed on nerve fibers of MP samples from the fundus, corpus and isthmian-cervical regions, with a successive morphometric quantification of OXT and ENK. None of the nerve fibers in the uterine fundus and corpus MPs contained ENK and the nerve fibers in the isthmian-cervical region demonstrated an ENK value of up to 94 ± 0.7 CU. A comparatively lower number of OXT-positive nerve fibers were found in the fundal MP (6.3 ± 0.8 CU). OXT-positive nerve fibers with OXT were marginally increased in corporal MP (15.0 ± 1.4 CU) and were substantially higher in the isthmian-cervical region MP (72.1 ± 5.1 CU) (p < 0.01). The distribution of OXY neurofibers showed a slight into the uterine corpus, while are highly present into the cervico-isthmic area, with influence on reproductive system and sexual disorders manifesting after surgical procedures on the cervix.

A new germline stop codon mutation in exon 15 of the APC gene predisposing to familial adenomatous polyposis.

Familial adenomatous polyposis (FAP) is an autosomal dominant disorder related to germline mutations of the adenomatous polyposis coli (APC) gene. It is characterized by the detection of numerous adenomatous polyps that, if untreated, develop into colorectal cancer. We studied an Italian family with FAP history and the related colorectal tumor sample of the proband. Sequencing analysis of blood samples revealed the presence of a never-reported germline mutation in the APC gene (exon 15): an heterozygous G deletion at position c.2126 resulting in a premature stop codon (p.Gly721GlufsX6) and in a truncated protein. This mutation was also identified in the colorectal tumor tissue, together with a second known pathogenic heterozygotic somatic mutation, c.4348C>T (p.Arg1450X), which generates a premature truncated protein. The novel identified germline mutation is therefore related to FAP and, in accordance with Knudson's "two hit" hypothesis, can be considered the first event predisposing to the insurgence of colorectal cancer in these patients. The somatic hit inactivating the second allele of the APC gene is located in the mutation cluster region of the gene; this is not a random event since it depends on the position of the germline mutation. The inactivation of APC generates the neoplastic growth advantage to the cell.

NT, NPY and PGP 9.5 presence in myomeytrium and in fibroid pseudocapsule and their possible impact on muscular physiology.

The uterine myoma pseudocapsule is a neurovascular bundle surrounding fibroid, containing neuropeptides, probably involved in uterine scar healing. We studied neurotensin (NT), neuropeptide tyrosine (NPY), and protein gene product 9.5 (PGP 9.5) nerve fibres in the pseudocapsule neurovascular bundle of intramural uterine fibroids on 67 no pregnant women by intracapsular myomectomy sparing the neurovascular bundle, sampling full thickness specimens of the pseudocapsule of uterine fibroids (PUF) and normal myometrium (NM) obtained from the fundus uteri (FU) and the uterine body (UB). The samples were sent for histological and immunofluorescent analyses and compared by morphometrical quantification. The Conventional Unit (C.U.) difference of NT, NPY, and PGP 9.5 nerve fibres was statistically analyzed. Our results showed that NT, NPY, and PGP 9.5 neurofibers are almost equally present in PUF as in NM of a no pregnant uterus. As all of these neuropeptides are present in the uterine muscle and can affect muscle contractility, uterine peristalsis and muscular healing. A myomectomy respecting the pseudocapsule neurofibers should facilitate smooth muscle scarring and promote restoration of normal uterine peristalsis with a possible positive influence on fertility.

The mRNA-HPV test utilization in the follow up of HPV related cervical lesions.

UNLABELLED: The biomolecular follow up of Human Papilloma Virus (HPV) is widely investigated in patients treated for HPV related cervical lesions, since the HPV-mRNA test is more specific and have a higher positive predictive value for CIN2-3 in triage of high risk (HR) women and in follow-up of women treated for CIN2/3. MATERIAL & METHODS: We investigated, during a 5 years' study, a cohort of patients divided in: group 1, patients at high risk for HPV-infections, and group 2, women diagnosed for CIN2/3, Cervicocarcinoma in situ (CIS) and Adenocarcinoma in situ (AIS) and surgically treated. The overall scheduled follow up was repeated each 6 months by: Pap Test, HPV-DNA test, m-RNA-HPV test and, in case of CIN2/3, CIS and AIS, also by colposcopy and biopsy. RESULTS: The follow up involved a total of 203 women: 85 women with mRNA-HPV positive test and 118 patients surgically treated for CIN2/3, CIS and AIS. In the group 1, the long term follow up detected, after one year, 32 positive mRNA-HR HPV women and, of these, after more than 2 years, 37.5% developed CIN1 and 21.8% developed CIN2/3. Similarly, in the follow up of group two, women with abnormal Pap test showed positivity of mRNA HR-HPV in 71.4% of cases even after 6 months; 65% of these developed a CIN1 within 2.5 years and 20% had CIN2/3 after 2.3 years. CONCLUSIONS: Study results indicate either that patients with mRNA HR-HPV positive controls, on average, after 12 months are all at risk of progression to CIN1 and CIN2/3, or the higher specificity of mRNA-HPV test than Pap Test in follow up of surgical treated patients. This investigation confirmed a strong association between HR mRNA-HPV presence and risk of neoplastic progression.

Ultrasound evaluation of uterine healing after laparoscopic intracapsular myomectomy: an observational study.

STUDY QUESTION: Can uterine scar healing after laparoscopic intracapsular myomectomy (LIM) be adequately monitored by traditional two-dimensional (2D) ultrasound (US) and Doppler velocimetry? SUMMARY ANSWER: The myometrial area of the scar after LIM can be followed by 2D US and Doppler velocimetry. WHAT IS KNOWN ALREADY: Apart from post-surgical adhesions, the main concern linked to laparoscopic myomectomy is the quality of healing of the myometrial incision: it has been suggested that US could be useful for assessing uterine scars after myomectomy. However, no diagnostic method has yet been widely accepted to assess the healing process. STUDY DESIGN, SIZE, DURATION: A cohort prospective study (level of evidence II-2), run in University-affiliated hospitals: 149 women with symptomatic uterine fibroids (UFs) underwent LIM, between January 2007 and October 2011. During follow up 13 patients withdrew from the study. PARTICIPANTS/MATERIALS, SETTING, METHODS: After LIM, all patients were followed by traditional 2D US scanning and Doppler velocimetry on Days: 0, 1, 7, 30 and 45. Authors evaluated: number, size and location of UFs, scar diameter and Doppler velocimetry and resistance index (RI) of the uterine arteries, at their ascending branch. MAIN RESULTS AND THE ROLE OF CHANCE: The uterine examination showed a significant (P < 0.05) progressive reduction of uterine scar area from 78% of the previous UF location on the first day, to 19% on 30th day, and <4% on the 45th day. There was no correlation with the size of the fibroid or the relative reduction in the size of the scar, on both Days 1 and 45. There was a significant (P < 0.05) increase in the RI of the ipsilateral uterine arteries from 0.65 on the first post-operative day to 0.83 after 7 days followed by a decrease to 0.71 on the 30th and 0.61 on the 45th post-operative day. LIMITATIONS, REASONS FOR CAUTION: This is a cohort investigation on a limited number of patients and it does not surgically compare LIM and 'classic' myomectomy in the scar US follow up. WIDER IMPLICATIONS OF THE FINDINGS: LIM avoided intraoperative bleeding and excessive tissue damage, as post-operative US follow up showed, with just two intra-myometrial hematomas (1.5%). The 2D US and Doppler velocimetry, a non-invasive safe method to check the myometrium after LIM, can detect post-operative hematoma and disechogenic, heterogeneous or ill-defined scar area, all unfavorable signs for myometrial scarring. Moreover, Doppler transvaginal monitoring, evaluating the pulsatility index (PI) and RI of the uterine arteries at their ascending branch, could identify patients with altered PI and RI parameters, possible markers of impaired wound healing.

Prevention of lymphocele in female pelvic lymphadenectomy by a collagen patch coated with the human coagulation factors: a pilot study.

BACKGROUND AND OBJECTIVES: The prevention of lymphoceles was tested using collagen patch coated with the human coagulation factors (TachoSil) on 58 consecutive patients with endometrial cancer who had undergone hysterectomy and pelvic lymphadenectomy (PL). METHODS: Patients were randomized in two groups: standard technique plus TachoSil (30 patients, group 1) and standard technique only (28, group 2). All surgical parameters were collected and patients underwent ultrasound examination on postoperative days 7, 14, and 28. The main outcome measures were: the development of symptomatic or asymptomatic lymphoceles, the need for further surgical intervention, as adverse effect of surgery and the drainage volume and duration. RESULTS: Same number of lymph nodes in both groups was removed; group 1 showed a lower drainage volume. Lymphoceles developed in 7 patients in group 1 and 16 in group 2, but only 3 were symptomatic in group 1 and 9 symptomatic in group 2, with statistical difference. Percutaneous drainage proved necessary in five cases: only one was in group 1 and four in group 2. CONCLUSIONS: Intraoperative application of TachoSil reduced rate of postoperative lymphocysts after PL, and it seems to provide a useful additional treatment option for reducing drainage volume and preventing lymphocele development after PL.

Laparoscopical management ovarian early sex cord-stromal tumors in postmenopausal women: a proposal method.

BACKGROUND: Ovarian sex-cord stromal tumor (SCST) comprises 5% of the ovarian neoplasm; it occurs as an ovarian mass or hemoperitoneum, and the surgical management of SCST is not well defined at early stage and in adult patients. PURPOSE OF THE STUDY: The authors tested to test the total not radical laparoscopic management of SCST in postmenopausal women at early stage. METHODS: Three postmenopausal women were admitted in University-affiliated hospitals for pelvic pain, ovarian complex mass and genital bleeding. Preoperative clinical and instrumental examination suspected an ovarian tumor; therefore, a total laparoscopic approach was attempted. All patients underwent laparoscopic oophorectomy with the frozen section, who suggested for ovarian SCST; one woman received a total laparoscopic hysterectomy plus other oophorectomy, two received only the complementary oophorectomy, all without intensive surgical staging by with pelvic and para-aortic lymphadenectomy, appendectomy, peritoneal biopsies, and omentectomy. RESULTS: All patients completed surgery without intrasurgical and postsurgical complications, with a fast dismissal. They are, currently, in long-term follow-up, with a 100% of survival after 3 years and with none morbility and morbidity. CONCLUSIONS: In order to fast restore and preserve women's integrity, total laparoscopic approach of early SCST in adult age, without intensive radical staging, could be an appropriate clinical choice, since these tumors at slow growth, recurring locally and only a long time after initial treatment. This minimally invasive management could be suggested in association with a long-term follow-up, as possible "wait and see" postoperative option.

Laparoscopical management of cornual pregnancies: a report of three cases.

OBJECTIVE: Cornual pregnancy refers to the implantation and development of a gestation in one of the upper and lateral portions of the uterus; authors report their experience in laparoscopic therapeutic procedures on three singleton cornual pregnancies. STUDY DESIGN: Three healthy women were admitted in General Hospitals with suspect of cornual pregnancies by clinical examination, increasing of beta-hCG value and transvaginal ultrasonography. One of them had a haemoperitoneum. Surgeons performed all operative laparoscopies, by incision and enucleating of ectopic cornual mass, coagulating of its surrounding vessels and suturing of the uterine incision site. RESULTS: Patients were successfully treated only by laparoscopy, post-operative recovery period was normal in all women, with no further therapeutically intervention in the follow-up course. The aftermath was uneventful at the follow-up of 2 years. CONCLUSION: In cornual pregnancies, the minimally invasive surgical treatment by salpingotomy or resection of the cornual region of the uterus and the suturing of the incision site, should be the option in women interested in future fertility.

Age-related pelvic floor modifications and prolapse risk factors in postmenopausal women.

OBJECTIVE: Genital prolapse is frequent in postmenopausal women; it describes the loss of support to the pelvic organs, resulting in a herniation of these into the vaginal channel. This problem affects 50% of parous women, and at least 50% of all women develop a mild form of genital prolapse after pregnancy. METHODS: An extensive literature review from 1990 to 2008 was performed on prolapse etiology and its risk factors; analyzing the data, we reviewed the genetic and biological aspects, age-related prolapse, biological tissue modifications, surgical problems, pelvic musculature modifications, and neuropathy. RESULTS: Data suggested that aging, pelvic trauma, and surgery evoke tissue denervation and devascularization, anatomic alterations, and increased degradation of collagen; all of these may lead to a decrease in mechanical strength and predispose an individual to prolapse. It has been demonstrated that there is a reduction in protein content and estrogens in uterosacral ligaments, in the vagina, and in the parametrium of women with prolapse. This is a possible explanation for why many surgical procedures to correct prolapse fail and recurrences after surgical correction are frequent. CONCLUSIONS: Even if the etiology of pelvic prolapse is poorly defined and multifactorial, aging risk factors, such as biomechanical abnormalities in connective tissue composition, hormonal deficiency, and irregular tissue metabolism, are nonmodifiable and therefore largely stated in clinical practice. Regardless of future developments, based on the reported findings, prolapse therapy will be more influenced by genetics, biological pelvic changes, changes in tissue homeostasis, and topical hormones, rather than general pelvic corrective surgical anatomy.

Subfascial hematomas and hemoperitoneum after cesarean section: prevalence according to closure and non-closure of the parietal peritoneum.

AIM: To compare early hemorrhagic complications and the surgical and clinical outcome in the closure and non-closure of the parietal peritoneum in cesarean section (CS) patients. MATERIAL AND METHODS: We retrospectively evaluated 2,576 post-CS women subdivided and compared in two groups by open and closed parietal peritoneum (group I, n = 1,580, group II, n = 996). RESULTS: The ultrasonographical detection of 23 blood collections (0.89%) was 14 in group I and 9 in group II, and of these we surgically treated 11 patients in group I and 8 patients in group II, with no statistical difference (p > 0.05); all group I patients showed hemoglobin point decreases and needed blood transfusions, with statistical significance (p < 0.05) linked to more severe early complications that make the post-CS outcome worse; no difference was confirmed in terms of antibiotic administration (p > 0.05). CONCLUSIONS: There was a significant increase of blood loss and transfusions in the first group. As the posterior surface of the Retzius space is open and if post-CS pathological bleeding occurs, blood can invade the peritoneal cavity causing a hemoperitoneum, with the possibility of hemorrhagic shock and a worse clinical outcome.

Abdominopelvic tuberculosis in gynaecology: laparoscopical and new laboratory findings.

INTRODUCTION: Tuberculosis (TB) is a rare curable infective disease, caused mainly by Mycobacterium tuberculosis, which in abdominopelvic (AP) localisation, can mimic a disseminated carcinomatosis. Symptoms of AP-TB are non-specific, so diagnosis is difficult and elusive as the affected patients have normal chest X-ray and elevated levels of CA125. Female ultrasonographic features of AP-TB mimic peritoneal carcinomatosis, and the computed tomography has also been suggested to be helpful, but the final diagnosis was reached by histology and serology. AIM OF THE STUDY: To propose the validity of the combination of laparoscopy (LPS), histopathology and enzyme-linked immuno-spot (ELIspot) in the diagnosis of AP-TB. METHODS: In the last two years, we had six women with suspect of AP-TB, who, after the routine exams, were referred for a diagnostic LPS that revealed turbid-free fluid in pelvis or ascites (collected for serology), multiple peritoneal and/or bowel tubercles (randomly sampled), fibrous bands, adhesions, hyperaemic and oedematous bowel loops. RESULTS: LPS diagnosis was confirmed by intra-LPS biopsy of nodules and histological examination of specimens: epithelioid granulomas with central caseous necrosis in five patients (83.3%) and a non-caseating granulomatous inflammation in the last one. An outer layer of epithelioid histiocytes and Langhans cells was present in all patients. Using the ELIspot technique performed on free fluids, the final diagnosis of TB was made in all patients. CONCLUSIONS: Even if gynaecological LPS appearance of the peritoneum can mimic other conditions, ELIspot and histopathological exam can confirm the suspect of AP-TB.