Liver tumours due to endometriosis and endometrial stromal sarcoma

BACKGROUND: Endometriosis can occur in unusual sites, liver involvement being first described in 1986. Extra-uterine malignant transformation in endometriosis has been reported, occurring mainly in the ovary. Liver involvement with endometrial stromal sarcoma (ESS) has not been previously reported. CASE OUTLINE: Two patients presenting with symptomatic liver masses related to endometriosis, who successfully underwent surgical intervention, are presented. CASE 1: A 31-year-old woman previously had been treated with hysterectomy and bilateral salpingoophorectomy for severe pelvic endometriosis. Six years later, she presented with malaise from bilobar liver involvement with endometrial deposits. She proceeded acutely to hilar obstruction with obstructive jaundice and portal vein thrombosis. CASE 2: A 59-year-old post-menopausal woman had earlier presented acutely from a ruptured mesenteric cyst, which showed features of endometrial stromal sarcoma (ESS). Two years later, she presented with symptoms from a large ESS occupying the right lobe. Discussion: Endometriosis per se, as well as malignant transformation into ESS can involve the liver.These should be considered in women with hepatic space occupying lesions of unknown etiology.     

线阵超声内镜对直肠子宫内膜异位症的诊断价值

目的:探讨线阵超声内镜对直肠子宫内膜异位症(rectal endometriosis,RE)的诊断价值.方法:对20例子宫内膜异位症患者于外科手术前行线阵超声内镜检查直肠,超声扫描频率为7.5MHz,根据直肠壁内有无边界不规则的低回声结节或团块判断直肠是否受累,并将超声内镜检查结果与手术中所见及术后病理进行比较.结果:20例患者中有12例经线阵超声内镜检查发现直肠壁内有异位子宫内膜病灶,其余8例患者的直肠壁正常.超声内镜诊断为RE的12例患者术中均见盆腔异位子宫内膜病灶与肠壁粘连紧密,手术切除的直肠病灶送检均见子宫内膜组织.超声内镜下未见直肠受累的8例患者盆腔子宫内膜异位病灶与肠壁无粘连或轻度粘连,易分离,分离缘组织送检未见子宫内膜组织.线阵超声内镜检查结果与手术中所见及术后病理完全一致.结论:线阵超声内镜检查是诊断RE的可靠方法,可对子宫内膜异位症患者是否伴有直肠受累做出准确的术前评估.     

Extracellularly signal-regulated kinase activity in the human endometrium: possible roles in the pathogenesis of endometriosis

Context: Endometriosis is an estrogen-dependent disease characterized by the presence of endometrial tissue outside of the uterine cavity, causing pelvic pain and infertility in 10% of reproductive-aged women. It is unclear why ectopic endometrium remains viable in only a subset of women. ERK1/2 plays key intracellular roles in activating cellular survival and differentiation processes. Objective: We sought to determine ERK1/2 activity in patients with endometriosis and its possible roles in regulating endometrial cell survival. Design: ERK1/2 phosphorylation and expression throughout the menstrual cycle were evaluated in vivo in normal and endometriotic human endometrium, and in vitro techniques assessed the steroidal regulation of ERK1/2 and its effect on endometrial cell survival. Results: Total ERK1/2 remained constant in normal and endometriotic endometrium throughout the menstrual cycle. Phospho-ERK1/2 was high in the late proliferative and secretory phases in normal endometrium (P < 0.05). In endometriotic glandular cells, there was no cyclical variation in phospho-ERK1/2. In endometriotic stromal cells, there was also a reduction in phospho-ERK1/2 variation, with higher levels in the early-mid secretory phase (P < 0.05). In cultured endometrial stromal cells (ESCs), estrogen plus progesterone increased ERK1/2 phosphorylation within 15 min (P < 0.05). Although estrogen alone did not induce ERK1/2 phosphorylation in normal ESCs, there was a significant response to estrogen in ESCs isolated from eutopic endometriotic endometrium (P < 0.05). ERK1/2 inhibition in ESCs reduced proliferation and increased apoptosis (P < 0.05). Conclusion: Abnormally high levels of ERK1/2 activity may be involved in endometriosis, possibly by stimulating endometrial cell survival.     

Endometrioma involving the perianal tissues: Report of a case

Summary and Conclusions Endometriosis may involve the uterine cavity (internal) or ectopic areas outside the uterus (external). The usual sites of external endometriosis are within the pelvic cavity. They include the ovary, peritoneal surface of the uterus, uterosacral ligaments, cul de sac, peritoneum, uterovesical peritoneum, the rectovaginal septum, the rectum, all parts of the colon, the appendix, and the ileum. Less common locations for ectopic endometriosis include the umbilicus, abdominal wall scars, the vulva, and the perineum. Endometriosis involving the perianal tissues is rare, and when found it is ussually located in the perineum at the site of previous episiotomy scars. The generally accepted explanation for the pathogenesis of external endometriosis is a combination of Sampson's⁶ retrograde-flow theory and the theory of metaplasia expounded by Gruenwald.³ A case of endometriosis involving the perianal tissues in a 29-year-old woman has been presented. The diagnosis was entertained prior to surgery because of the relationship of the symptoms to the patient's menstrual cycle, but confirmation of the diagnosis depended upon pathologic study of the tumor mass, which showed endometrial glands and stroma typical of endometriosis. Read at the meeting of the Pennsylvania Society of Colon and Rectal Surgery in conjunction with the Sectional Meeting of the Pennsylvania State Medical Society, Lancaster, Pennsylvania, November 18, 1970.     

Rectovaginal fistula after STARR procedure complicated by haematoma of the posterior vaginal wall: report of a case

We report the case of a patient treated with the stapled transanal rectal resection (STARR) procedure for obstructed defecation, who developed an early postoperative haematoma of the posterior vaginal wall and, after 30 days, a rectovaginal fistula (RVF), even though the intervention had been performed according to the standardized technique. After clinical examination and three-dimensional anal endosonography, we carried out a successful surgical correction with double vaginal and rectal flaps with repair of the rectovaginal septum and without faecal diversion. The STARR procedure, even if performed according to a rigorous application of the methodological standards, may be followed by a RVF possibly due to a blood collection leading to ischaemia of the vaginal wall.     

Rectovaginal septum endometriosis: a disease with specific diagnosis and treatment

BACKGROUND: The involvement of the rectovaginal septum, of rectum and sigmoid by endometriosis leads to intense symptoms as dysmenorrhea, pelvic pain, deep dyspareunia, tenesmus and hematochezia in young and middle aged women during periods. The diagnosis can be made by tipycal history and vaginal examination, rectal examination, barium enema, proctoscopy and so on. The indications of operation include severe clinic symptoms and failed conservative therapy. The treatment of choice for this type of endometriosis is the surgical resection of affected tissue, in order to relieve patient symptoms, and avoid disease progression. The correct assessment as to the presence and extension of the endometriosis-affected sites such as the rectum, uterosacral ligaments and rectovaginal septum is extremely important to provide better results with the surgical treatment of endometriosis. AIM: To describe the main aspects related to rectovaginal septum endometriosis and offer the general surgeon some information about this enigmatic disease. CONCLUSION: Rectovaginal septum endometriosis is a frequent disease, with specific diagnosis and treatment.     

Prevention of Anovaginal Fistula during Double-Stapling of Ileal Pouch-Anal Anastomosis

Abstract Recto- or anovaginal fistula is a troublesome complication of double-stapling technique in ultralow rectal anastomosis for rectal cancer or in ileal pouch-anal anastomosis for ulcerative colitis. In this study, a technique for preventing this problem by means of separation of the vaginal wall during the stapler firing is described using a flexible spatula introduced through the rectovaginal septum into the peritoneal cavity.     

Combined perineal and endorectal repair of rectocele by circular stapler: a novel surgical technique

PURPOSE: The aim of this study was to present a new technique for treatment of disabling rectocele when associated with internal mucosal prolapse or hemorrhoids using a 33-mm circular stapler. METHODS: Eight female patients complaining of obstructed defecation because of distention rectocele associated with internal mucosal prolapse or hemorrhoids and perineal descent entered the study. The rectovaginal septum was opened by diathermy up to the end of the rectal wall weakness. The perineal wound and the anus were held open by a self-retractor. Using a transparent anoscope (PPH 01 system), 2 mucosal pursestrings were prepared 5 and 8 to 9 cm distant from the dentate line. Posteriorly, only the submucosa was included in the pursestring; anteriorly, it included the rectal wall, which was kept separate from the vaginal wall. A transanal 33-mm circular stapler was then used to close the rectocele and treat the mucosal prolapse. Before closing the perineum a levatorplasty was fashioned. RESULTS: One patient had a vaginal tear during dissection of the septum, which healed spontaneously in one month. No other complications were recorded. Postoperative defecography showed correction of the rectocele and the posterior rectal prolapse in all patients. In two of them, a small lateral diverticulum could be seen, although this was asymptomatic. After a median follow-up of 12 months, all had significantly improved defecation (chronic constipation score dropped from 14.3 to 5, P < 0.04). CONCLUSION: Combined perineal and endorectal stapler repair of rectocele may be a useful new surgical tool for correcting distention rectocele associated with mucosal prolapse or hemorrhoids and perineal descent in selected patients. A longer follow-up on a larger number of patients is needed to confirm these preliminary results.     

Endometriosis of the intestines: A report of seven cases

Summary and Conclusions In a series of 720 cases of histologically verified endometriosis filed at this hospital in a 20-year period, seven cases of intestinal endometriosis were found: four in appendiceal locations, one in the terminal ileum, one in the rectovaginal septum, and one in the cecum. Two of these patients had concurrent involvement of the uterus and adnexa, and in the remaining patients the lesions were limited to the intestines. No patient had clinical signs and symptoms of endometriosis, and even diagnosis was established by pathologic examination of the lesion. In two of the cases included in this series, the patients were post menopausal; these cases illustrate the point that aberrant endometrial tissue may become activated after the menopause. Embryology gives support to the view that peritoneum, germinal epithelium and uterine epithelium are all derivatives of coelomic epithelium. In all our cases the endometrial implants were subserosal. This presupposes the persistence in the subcoelomic mesenchyma of undifferentiated stem cells capable of differentiating into endometrial tissue.     

Chronic obstruction of the inferior vena cava with recurrent endometrial stromal sarcoma

A 64-year-old woman presented with endometrial stromal sarcoma of the inferior vena cava. The tumor was removed along the venous wall, and the vena cava and the right renal vein were reconstructed with a ringed polytetrafluoroethylene (PTFE) graft. The patient remains well 9 months after the operation despite graft occlusion. Fifteen years earlier the patient had undergone a hysterectomy for endometrial stromal sarcoma. Histologically, the second tumor was identical with the endometrial stromal sarcoma removed with the uterus at the primary operation. To the best of our knowledge, this is the first report of a case of obstruction of the inferior vena cava by such a tumor.     

Rectovaginal septal repair: case presentations and introduction of a modified reconstruction technique

Abstract Rectovaginal fistula are a relatively rare kind of anorectal fistulas. Spontaneous healing is rare and the rectal advancement flap repair is the most popular procedure with success rates ranging between 60% and 80%. We present a new technique for repairing damage in the rectovaginal septum that consists of placing a folded polyglycolic acid mesh (Dexon) between the levator ani muscle closure area and the vaginal wall. This absorbable mesh separates the suture lines on the vaginal and rectal walls, and induces fibrosis and healing. The technique was performed in four women suffering from a rectovaginal fistula due to different causes. It was successful in all cases.     

Progesterone resistance in endometriosis: link to failure to metabolize estradiol

Endometriosis is the most common cause of pelvic pain and affects an estimated 5 million women in the US. The biologically active estrogen estradiol (E2) is the best-defined mitogen for the growth and inflammation processes in the ectopic endometriotic tissue that commonly resides on the pelvic organs. Progesterone and progestins may relieve pain by limiting growth and inflammation in endometriosis but a portion of patients with endometriosis and pelvic pain do not respond to treatment with progestins. Moreover, progesterone-induced molecular changes in the eutopic (intrauterine) endometrial tissue of women with endometriosis are either blunted or undetectable. These in vivo observations are indicative of resistance to progesterone action in endometriosis. The molecular basis of progesterone resistance in endometriosis may be related to an overall reduction in the levels of progesterone receptors (PRs) and the lack of the PR isoform named progesterone receptor B (PR-B). In normal endometrium, progesterone acts on stromal cells to induce secretion of paracrine factor(s). These unknown factor(s) act on neighboring epithelial cells to induce the expression of the enzyme 17beta-hydroxysteroid dehydrogenase type 2 (17beta-HSD-2), which metabolizes the biologically active estrogen E2 to estrone (E1). In endometriotic tissue, progesterone does not induce epithelial 17beta-HSD-2 expression due to a defect in stromal cells. The inability of endometriotic stromal cells to produce progesterone-induced paracrine factors that stimulate 17beta-HSD-2 may be due to the lack of PR-B and very low levels of progesterone receptor A (PR-A) observed in vivo in endometriotic tissue. The end result is deficient metabolism of E2 in endometriosis giving rise to high local concentrations of this local mitogen. The cellular and molecular mechanisms underlying progesterone resistance and failure to metabolize E2 in endometriosis are reviewed.     

Regulation of aromatase P450 expression in endometriotic and endometrial stromal cells by CCAAT/enhancer binding proteins (C/EBPs): decreased C/EBPbeta in endometriosis is associated with overexpression of aromatase

In human endometriotic stromal cells, markedly high levels of aromatase P450 (P450arom) mRNA and promoter II activity are present and can be vigorously stimulated by PGE(2) via a cAMP-dependent pathway to give rise to physiologically significant estrogen biosynthesis. Stromal cells of eutopic endometrium, on the other hand, do not express sufficient levels of P450arom for detectable enzyme activity. Because P450arom is up-regulated in the ovaries of CCAAT/enhancer binding protein (C/EBP) beta knockout mice and activation of the ovarian-type P450arom promoter (II) is responsible for aberrant P450arom expression in endometriosis, we sought here to evaluate the possible roles of C/EBP isoforms in the regulation of P450arom expression in endometriotic vs. eutopic endometrial stromal cells. We previously found that the -517-bp flanking region of promoter II contained the critical cis-acting elements for baseline and cAMP (analog)-induced activity. In this study, we disrupted several potential sequences and found that mutations of a -211/-197-bp cAMP-response element (CRE) and a -317/-304-bp C/EBP binding site abolished both baseline and cAMP-induced promoter II activity. Ectopic expression of C/EBPalpha increased both baseline and cAMP-dependent promoter II activity significantly in endometriotic cells, whereas ectopic expression of C/EBPbeta or C/EBPdelta abolished promoter II activity in both untreated and cAMP-treated endometriotic stromal cells. Comparable changes in promoter II activity were observed using endometrial stromal cells, which showed, however, seemingly diminished levels of baseline and cAMP-induced promoter II activity in comparison with endometriotic cells. EMSA using a probe containing the critical -317/-304-bp C/EBP site upstream of promoter II demonstrated a distinct DNA-protein complex in endometriotic, but not in endometrial stromal cells. This specific complex, however, could not be altered using antibodies against C/EBPalpha, -beta, or -delta. Because CRE is another potential DNA motif that can bind C/EBP isoforms, we next used EMSA using a probe containing the -211/-197-bp CRE and demonstrated that specific DNA-protein complexes contained C/EBPalpha but not C/EBPbeta or C/EBPdelta in endometriotic stromal cells. In contrast, C/EBPbeta and C/EBPdelta but not C/EBPalpha were detected in DNA-protein complexes using nuclear extracts from endometrial stromal cells. Western blotting and immunohistochemistry demonstrated expression of C/EBPalpha, -beta, and -delta in human endometriotic and endometrial stroma and epithelium. Intriguingly, C/EBPbeta was expressed at increased levels in stromal cells of human eutopic endometrium compared with simultaneously biopsied endometriotic tissues. We conclude that both -317/-304 and -211/-197-bp elements in promoter II are critical for the robust cAMP-dependent induction in endometriosis. C/EBPalpha up-regulates, whereas C/EBPbeta and C/EBPdelta inhibit P450arom promoter activity via binding primarily to the -211/-197-bp CRE under in vitro conditions. In vivo down-regulation of C/EBPbeta in endometriotic stromal cells and its up-regulation in endometrial stromal cells may in part account for the induction of P450arom expression in endometriosis and its inhibition in endometrium.     

Endoluminal ultrasound diagnosis and operative management of rectal endometriosis

PURPOSE: Endorectal ultrasound was performed in patients with endometriosis to evaluate the role of this technique for rectal wall involvement and to evaluate the position of preoperative diagnosis in the operative management of rectal endometriosis. METHODS: Sixteen patients with suspected fixation of endometriomas to the rectal wall during bimanual examination were included in the study. Endorectal ultrasound was performed using a real time unit with a 7.5 MHz endorectal transducer. The probe was introduced via a rectoscope into the rectum up to the rectosigmoid. RESULTS: Endometriosis was confirmed histopathologically in all patients. In six patients rectal wall involvement was diagnosed, in two patients endometriomas were adjacent to the rectal wall, and in eight patients rectal wall involvement could be excluded. Preoperative diagnosis was confirmed in all patients during operation. Laparotomy was performed in those patients with preoperatively diagnosed rectal wall involvement, whereas the remaining patients were treated laparoscopically. Endometriomas with rectal wall involvement were treated in five of six patients with resection of the affected bowel predominantly by low anterior resection. CONCLUSIONS: Preoperative endorectal ultrasound is a reliable technique to visualize perirectal endometriomas and to assess rectal wall involvement. Based on preoperative endosonographic diagnosis, an operative management was established with laparotomy and resection of the affected bowel in cases of rectal wall involvement.     

Bowel endometriosis: Colorectal surgeon’s perspective in a multidisciplinary surgical team

Endometriosis is a gynecological condition that presents as endometrial-like tissue outside the uterus and induces a chronic inflammatory reaction. Up to 15% of women in their reproductive period are affected by this condition. Deep endometriosis is defined as endometriosis located more than 5 mm beneath the peritoneal surface. This type of endometriosis is mostly found on the uterosacral ligaments, inside the rectovaginal septum or vagina, in the rectosigmoid area, ovarian fossa, pelvic peritoneum, ureters, and bladder, causing a distortion of the pelvic anatomy. The frequency of bowel endometriosis is unknown, but in cases of bowel infiltration, about 90% are localized on the sigmoid colon or the rectum. Colorectal involvement results in alterations of bowel habits such as constipation, diarrhea, tenesmus, dyschezia, and, rarely, rectal bleeding. Differential diagnosis must be made in case of irritable bowel syndrome, solitary rectal ulcer syndrome, and a rectal tumor. A precise diagnosis about the presence, location, and extent of endometriosis is necessary to plan surgical treatment. Multidisciplinary laparoscopic treatment has become the standard of care. Depending on the size of the lesion and site of involvement, full-thickness disc excision or bowel resection needs to be performed by an experienced colorectal surgeon. Long-term outcomes, following bowel resection for severe endometriosis, regarding pain and recurrence rate are good with a pregnancy rate of 50%.     

Cyclooxygenase-2 regulates survival, migration, and invasion of human endometriotic cells through multiple mechanisms

Endometriosis is a debilitating disease characterized by the presence of functional endometrial glandular epithelium and stroma outside the uterine cavity that affects up to 20% of women of child-bearing age. Cyclooxygenase-2 (COX-2), a rate-limiting enzyme in the biosynthesis of prostaglandin E(2) (PGE(2)), is highly expressed in endometriotic tissues and results in increased concentrations of peritoneal PGE(2) in women. In this study, we determined the expression of COX-2 protein in ectopic and eutopic endometria in humans and the role of COX-2 in endometriotic cell survival, migration, and invasion in humans. Our results indicate that COX-2 protein is abundantly expressed in ectopic endometria compared with eutopic endometria. Comparatively, expression of COX-2 protein is higher in eutopic endometria from women with endometriosis compared with women without endometriosis. Inhibition of COX-2 decreases survival, migration, and invasion of endometriotic cells that are associated with decreased production of PGE(2). Cell growth inhibitory effects of COX-2 inhibition/silencing are mediated through nuclear poly (ADP-ribose) polymerase-mediated apoptosis. Cell motility and invasion inhibitory effects of COX-2 inhibition/silencing are mediated through matrix metalloproteinase-2 and -9 activities. Interestingly, effects of COX-2 inhibition is more profound in endometriotic epithelial than in stromal cells. Furthermore, inhibition of COX-2 affects invasion rather than migration of endometriotic epithelial and stromal cells. It is the first evidence showing that inhibition of COX-2 decreases endometriotic epithelial and stromal cell survival, migration, and invasion in humans. Our results support the emerging concept that COX-2/PGE(2) promotes the pathophysiology and pathogenesis of endometriosis in humans.     

Hepatocyte growth factor/Met system promotes endometrial and endometriotic stromal cell invasion via autocrine and paracrine pathways

Endometrial stromal cells reportedly have a role in the initial invasion of endometrial tissue into the peritoneum. Hepatocyte growth factor (HGF), which is a ligand for the c-met protooncogene product (Met), stimulates proliferation and invasion of a large number of cells. In this study we investigated the role of the HGF/Met system in the pathogenesis of endometriosis. HGF concentrations in the peritoneal fluid of patients with endometriosis were significantly higher than in those without endometriosis and correlated positively with revised American Society of Reproductive Medicine scores. We showed that the peritoneum and endometriotic stromal cells may be major sources of HGF in peritoneal fluid. Endometrial and endometriotic stromal cells expressed the Met receptor, which was activated by endogenous and exogenous HGF. HGF enhanced stromal cell proliferation and invasion. We also demonstrated that the HGF-stimulated stromal cell invasion was due in part to the induction of urokinase-type plasminogen activator, a member of the extracellular proteolysis system. In conclusion, the HGF/Met system is involved in the pathogenesis of endometriosis by promoting stromal cell proliferation and invasion of shed endometria and endometrial lesions via autocrine and paracrine pathways.     

Tumor necrosis factor-alpha promotes proliferation of endometriotic stromal cells by inducing interleukin-8 gene and protein expression

Endometriosis, a common disease among women of reproductive age, is characterized by the presence of endometrial-like tissue outside the uterus. We and others showed that several cytokine levels, including interleukin-8 (IL-8) and tumor necrosis factor-alpha (TNFalpha), are elevated in the peritoneal fluid of women with endometriosis compared with those in women without endometriosis. We also demonstrated that the addition of IL-8 to the culture medium stimulated the proliferation of cultured endometriotic stromal cells. TNFalpha is a multipotent cytokine that induces IL-8 production in various cell types. Therefore, we hypothesized that TNFalpha may also contribute to the pathogenesis of endometriosis by inducing the production of IL-8. To test this hypothesis, we analyzed the peritoneal fluid concentrations of IL-8 and TNFalpha using enzyme-linked immunosorbent assay (ELISA). We observed a significant correlation between the levels of TNFalpha and IL-8 in the peritoneal fluid of endometriosis patients. We also obtained the endometriotic stromal cells from chocolate cyst linings of the ovary. The expression of the receptors for TNFalpha (TNFR) was examined by RT-PCR. We observed the expression of both TNFR-I and TNFR-II genes in endometriotic stromal cells. The expression of IL-8 gene and protein was analyzed by Northern blot hybridization and enzyme-linked immunosorbent assay, respectively. TNFalpha induced the gene and protein expression of IL-8 in endometriotic stromal cells in a dose-dependent fashion. The addition of TNFalpha promoted the proliferation of the endometriotic stromal cells, and the stimulatory effects of TNFalpha were abolished by adding anti-IL-8 antibody. We demonstrated for the first time that TNFalpha stimulated proliferation of endometriotic stromal cells through induction of IL-8 gene and protein expression. We concluded that the TNFalpha may be one of the essential factors for the pathogenesis of endometriosis.