Unraveling the role of Epac1-SOCS3 signaling in the development of neonatal-CRD-induced visceral hypersensitivity in rats.

AIMS: Visceral hypersensitivity in irritable bowel syndrome (IBS) is widespread, but effective therapies for it remain elusive. As a canonical anti-inflammatory protein, suppressor of cytokine signaling 3 (SOCS3) reportedly relays exchange protein 1 directly activated by cAMP (Epac1) signaling and inhibits the intracellular response to inflammatory cytokines. Despite the inhibitory effect of SOCS3 on the pro-inflammatory response and neuroinflammation in PVN, the systematic investigation of Epac1-SOCS3 signaling involved in visceral hypersensitivity remains unknown. This study aimed to explore Epac1-SOCS3 signaling in the activity of hypothalamic paraventricular nucleus (PVN) corticotropin-releasing factor (CRF) neurons and visceral hypersensitivity in adult rats experiencing neonatal colorectal distension (CRD). METHODS: Rats were subjected to neonatal CRD to simulate visceral hypersensitivity to investigate the effect of Epac1-SOCS3 signaling on PVN CRF neurons. The expression and activity of Epac1 and SOCS3 in nociceptive hypersensitivity were determined by western blot, RT-PCR, immunofluorescence, radioimmunoassay, electrophysiology, and pharmacology. RESULTS: In neonatal-CRD-induced visceral hypersensitivity model, Epac1 and SOCS3 expressions were downregulated and IL-6 levels elevated in PVN. However, infusion of Epac agonist 8-pCPT in PVN reduced CRF neuronal firing rates, and overexpression of SOCS3 in PVN by AAV-SOCS3 inhibited the activation of PVN neurons, reduced visceral hypersensitivity, and precluded pain precipitation. Intervention with IL-6 neutralizing antibody also alleviated the visceral hypersensitivity. In naïve rats, Epac antagonist ESI-09 in PVN increased CRF neuronal firing. Consistently, genetic knockdown of Epac1 or SOCS3 in PVN potentiated the firing rate of CRF neurons, functionality of HPA axis, and sensitivity of visceral nociception. Moreover, pharmacological intervention with exogenous IL-6 into PVN simulated the visceral hypersensitivity. CONCLUSIONS: Inactivation of Epac1-SOCS3 pathway contributed to the neuroinflammation accompanied by the sensitization of CRF neurons in PVN, precipitating visceral hypersensitivity and pain in rats experiencing neonatal CRD.

Plasminogen activator inhibitor-1 (PAI-1) expression in endometriosis.

PURPOSE: Deep infiltrating endometriosis (DIE) is defined as an endometriotic lesion penetrating to a depth of >5 mm and is associated with pelvic pain, but the underlying mechanisms are unclear. Our objective is to investigate whether plasminogen activator inhibitor-1 expression (PAI-1) in endometriotic tissues is increased in women with DIE. METHODS: In this blinded in vitro study, immunohistochemistry and Histoscore were used to examine the expression of PAI-1 in glandular epithelium (GECs) and stroma (SCs) in a total of 62 women: deep infiltrating uterosacral/rectovaginal endometriosis (DIE; n = 13), ovarian endometrioma (OMA; n = 14), superficial peritoneal uterosacral/cul-de-sac endometriosis (SUP; n = 23), uterine (eutopic) endometrium from women with endometriosis (UE; n = 6), and non-endometriosis eutopic endometrium (UC; n = 6). The following patient characteristics were also collected: age, American Fertility Society stage, hormonal suppression, phase of menstrual cycle, dysmenorrhea score and deep dyspareunia score. RESULTS: PAI-1 expression in GECs and SCs of the DIE group was significantly higher than that of SUP group (p = 0.01, p = 0.01, respectively) and UE group (p = 0.03, p = 0.04, respectively). Interestingly, increased PAI-1 expression in GECs and SCs was also significantly correlated with increased dysmenorrhea (r = 0.38, p = 0.01; r = 0.34, p = 0.02, respectively). CONCLUSIONS: We found higher expression of PAI-1 in DIE, and an association between PAI-1 and worse dysmenorrhea.

Intramucosal fat is uncommon in large bowel polyps but raises three differential diagnoses.

AIMS: This case series intends to expand currently limited knowledge regarding the existence and diagnostic significance of intramucosal fat in colorectal polyps. METHODS: Clinicopathological features of nine such polyps were reported following histopathological review, including S100 and EMA immunohistochemistry. RESULTS AND CONCLUSIONS: Such review subdivided seven polyps into three groups: (1) mucosal perineurioma/serrated polyps with fat among the perineurial stroma (three cases); (2) submucosal lipomas with adipose tissue extending into the overlying mucosa (two cases) and (3) polyps with intramucosal adipose tissue only, that is, the newly described but less-recognised entity known as intramucosal lipoma (two cases). The two remaining polyps of this series did not include submucosa but, from assessing their muscularis mucosae, were favoured to represent intramucosal lipomas. The first two phenomena are formally described for the first time by this case series. The last of these three diagnoses should prompt investigations for Cowden syndrome, but intramucosal lipomas are more often sporadic/non-syndromic.

Downregulation of neuronal vasoactive intestinal polypeptide in Parkinson's disease and chronic constipation.

BACKGROUND: Chronic constipation (CC) is a common and severe gastrointestinal complaint in Parkinson's disease (PD), but its pathogenesis remains poorly understood. This study evaluated functionally distinct submucosal neurons in relation to colonic motility and anorectal function in PD patients with constipation (PD/CC) vs both CC and controls. METHODS: Twenty-nine PD/CC and 10 Rome III-defined CC patients were enrolled. Twenty asymptomatic age-sex matched subjects served as controls. Colonic transit time measurement and conventional anorectal manometry were evaluated in PD/CC and CC patients. Colonoscopy was performed in all three groups. Colonic submucosal whole mounts from PD/CC, CC, and controls were processed for immunohistochemistry with antibodies for vasoactive intestinal polypeptide (VIP) and peripheral choline acetyltransferase, markers for functionally distinct submucosal neurons. The mRNA expression of VIP and its receptors were also assessed. KEY RESULTS: Four subgroups of PD/CC patients were identified: delayed colonic transit plus altered anorectal manometry (65%); delayed colonic transit (13%); altered manometric pattern (13%); and no transit and manometric impairment (9%). There were no differences in the number of neurons/ganglion between PD/CC vs CC or vs controls. A reduced number of submucosal neurons containing VIP immunoreactivity was found in PD/CC vs controls (P<.05). VIP, VIPR1, and VIPR2 mRNA expression was significantly reduced in PD/CC vs CC and controls (P<.05). CONCLUSIONS AND INFERENCES: Colonic motor and rectal sensory functions are impaired in most PD/CC patients. These abnormalities are associated with a decreased VIP expression in submucosal neurons. Both sensory-motor abnormalities and neurally mediated motor and secretory mechanisms are likely to contribute to PD/CC pathophysiology.

Rectal mucosal endometriosis primarily misinterpreted as adenocarcinoma: a case report and review of literature.

Endometriosis involving intestinal mucosa is relatively uncommon. It poses a diagnostic challenge for clinicians and pathologists. We herein report a case of colonoscopic specimen revealing rectal mucosal endometriosis. A 39-year-old woman complained of red rectal bleeding and intermittent abdominal pain. Colonoscopic examination showed a rectal mass with ulceration and circum wall involvement. Biopsy was processed in the suspicious of carcinoma. Morphologically, irregular glands replaced residual colorectal ones, displayed mucin depletion, nuclear stratification and subtile subnuclear vacuoles. The stroma was full of spindle cells with abundant pink cytoplasm and unclear boundary. Due to subjectively interpreting as dysplastic glands in desmoplastic setting, primary rectal adenocarcinoma was firstly raised. Immunohistochemically, CK7, ER and CD10 identified the essence of ectopic endometrium. CK20 and CDX2 highlighted residual glands. In case of misdiagnosis, any pathologists should be aware of intestinal endometriosis for each female's colorectal biopsy, especially for that morphology not typical for primary adenocarcinoma or endometriosis. Reading slides carefully combined with a panel of immunomarkers would solve the pitfall.

Use of hormonal therapy is associated with reduced nerve fiber density in deep infiltrating, rectovaginal endometriosis.

OBJECTIVE: To study the density of nerve fibers in cases of deep infiltrating endometriosis (DIE) of the rectovaginal septum in relation to various clinical factors. DESIGN: A research laboratory-based study. SETTING: A tertiary center together with a research laboratory. METHODS: Archived DIE tissue samples from 45 women operated upon for rectovaginal septum DIE were re-examined histologically, and by immunohistochemistry. MAIN OUTCOME MEASURES: The effect of progestogens or combined oral contraceptives on the density of nerve fibers, and the expression of nerve growth factor (NGF) and its high-affinity receptor (tyrosine kinase receptor A, Trk-A). RESULTS: The use of hormonal therapy was associated with reduced densities of sympathetic, parasympathetic and sensory nerve fibers in DIE lesions. Density of total nerve fibers (with pan-neuronal marker PGP9.5) was significantly lower (p < 0.05) in lesions collected from hormone-treated women (8.6/mm², 4.2-20.8/mm²; median density, from 25th to 75th quartiles) compared with that in lesions from untreated women (24.9/mm², 11.2-34.9/mm²). DIE lesions stained strongly for NGF and its receptor Trk-A. Expression of NGF, but not of Trk-A, was significantly reduced during use of hormonal therapy. CONCLUSIONS: Use of hormonal therapy was associated with significantly reduced nerve fiber density in DIE lesions. This may be an important mechanism of action of hormonal therapy for controlling DIE pain symptoms. The expression of estrogen-regulated NGF and its receptor was only partially suppressed during the use of hormonal therapy, suggesting that local estrogen action is often maintained during conventional hormonal therapy in cases of DIE.

Exploring Metabolic Profile Differences between Colorectal Polyp Patients and Controls Using Seemingly Unrelated Regression.

Despite the fact that colorectal cancer (CRC) is one of the most prevalent and deadly cancers in the world, the development of improved and robust biomarkers to enable screening, surveillance, and therapy monitoring of CRC continues to be evasive. In particular, patients with colon polyps are at higher risk of developing colon cancer; however, noninvasive methods to identify these patients suffer from poor performance. In consideration of the challenges involved in identifying metabolite biomarkers in individuals with high risk for colon cancer, we have investigated NMR-based metabolite profiling in combination with numerous demographic parameters to investigate the ability of serum metabolites to differentiate polyp patients from healthy subjects. We also investigated the effect of disease risk on different groups of biologically related metabolites. A powerful statistical approach, seemingly unrelated regression (SUR), was used to model the correlated levels of metabolites in the same biological group. The metabolites were found to be significantly affected by demographic covariates such as gender, BMI, BMI(2), and smoking status. After accounting for the effects of the confounding factors, we then investigated potential of metabolites from serum to differentiate patients with polyps and age matched healthy controls. Our results showed that while only valine was slightly associated, individually, with polyp patients, a number of biologically related groups of metabolites were significantly associated with polyps. These results may explain some of the challenges and promise a novel avenue for future metabolite profiling methodologies.

Trend and risk factors of diverticulosis in Japan: age, gender, and lifestyle/metabolic-related factors may cooperatively affect on the colorectal diverticula formation.

BACKGROUND: Despite the marked increase of diverticulosis, its risk factors have not been adequately elucidated. We therefore aim to identify significantly associated factors with diverticulosis. We also aim to investigate the present state of diverticulosis in Japan. METHODS: We reviewed the medical records from 1990 to 2010 that included the data of consecutive 62,503 asymptomatic colonoscopy examinees from the general population in Japan. Most recent 3,327 examinees were analyzed with 16 background factors. RESULTS: Among the 62,503 subjects (47,325 men and 15,178 women; 52.1 ± 9.2 years old), diverticulosis was detected in 11,771 subjects (18.8%; 10,023 men and 1,748 women). The incidences of diverticulosis in 1990-2000 and 2001-2010 were respectively 13.0% (3,771 of 29,071) and 23.9% (8,000 of 33,432): the latter was much higher than the former in all age groups and for both genders. Considering the anatomical locations of colorectal diverticula, left-sided ones have markedly increased with age but not significantly changed with times. Univariate analyses of the 3,327 subjects showed significant association of diverticulosis with four basic factors (age, sex, body mass index, blood pressure), three life style-related factor (smoking, drinking, severe weight increase in adulthood), and two blood test values (triglyceride, HbA1c). The multiple logistic analysis calculating standardized coefficients (ß) and odds ratio (OR) demonstrated that age (ß = 0.217-0.674, OR = 1.24-1.96), male gender (ß = 0.185, OR = 1.20), smoking (ß = 0.142-0.200, OR = 1.15-1.22), severe weight increase in adulthood (ß = 0.153, OR = 1.17), HbA1c (ß = 0.136, OR = 1.15), drinking (ß = 0.109, OR = 1.11), and serum triglyceride (ß = 0.098, OR = 1.10) showed significantly positive association with diverticulosis whereas body mass index and blood pressure did not. CONCLUSIONS: The large-scale data of asymptomatic colonoscopy examinees from the general population from 1990 to 2010 indicated that the prevalence of diverticulosis is still increasing in Japan. Age, male gender, smoking, severe weight increase in adulthood, serum HbA1c, drinking, and serum triglyceride showed significant positive association with diverticulosis.

Rectal tonsil: a case report and literature review.

The rectal tonsil, a reactive proliferation of lymphoid tissue located in the rectum, is rare. Histologically, benign lymphoid hyperplasia of the rectum is usually characterized by large lymphoid follicles with active germinal centers and a narrow surrounding mantle zone and marginal zone. This lesion is benign, but must be differentiated from the polypoid type of mucosa-associated lymphoid tissue lymphomas. In the current paper, we present a case of rectal tonsil in a 59-year-old woman. We describe the endoscopic ultrasound imaging findings with literature review.

The relationship among HOXA10, estrogen receptor α, progesterone receptor, and progesterone receptor B proteins in rectosigmoid endometriosis: a tissue microarray study.

BACKGROUND: Very few studies have evaluated the expression of homeobox A10 (HOXA10) and steroid (estrogen and progesterone) receptors exclusively in deep endometriosis. Conclusions drawn from studies evaluating peritoneal and ovarian endometriosis are usually generalized to explain the pathogenesis of the disease as a whole. We aimed to evaluate the expression of HOXA10, estrogen receptor α (ER-α), progesterone receptor (PR), and PR-B in rectosigmoid endometriosis (RE), a typical model of deep disease. METHODS: We used RE samples from 18 consecutive patients to construct tissue microarray blocks. Nine patients each were operated during the proliferative and secretory phases of the menstrual cycle. We quantified the expressions of proteins by immunohistochemistry using the modified Allred score. RESULT: The HOXA10 was expressed in the stroma of nodules during the secretory phase in 5 of the 18 patients. Expression of ER-α (in 16 of 18 patients), PR (in 17 of 18 patients), and PR-B (17 of 18 patients) was moderate to strong in the glands and stroma of nodules during both phases. Expression of both PR (P = .023) and PR-B (P = .024) was significantly greater during the secretory phase. CONCLUSION: The HOXA10 is expressed in RE, where it likely imparts the de novo identity of endometriotic lesions. The ER-α, PR, and PR-B are strongly expressed in RE, which differs from previous studies investigating peritoneal and ovarian lesions. This suggests different routes of pathogenesis for each of the 3 types of endometriosis.

Expressão de mediadores neurotróficos e pró-inflamatórios na endometriose de reto e sigmoide / Expression of neurotrophic and inflammatory mediators in rectosigmoid endometriosis

OBJETIVO: Avaliar a expressão de mediadores neurotróficos (NGF, NPY E VIP) e pró-inflamatórios (TNF-α) em fragmentos de reto e sigmoide comprometidos por endometriose. MÉTODOS: Foram selecionadas 24 pacientes submetidas ao tratamento cirúrgico de endometriose de reto e sigmoide com técnica de ressecção segmentar, seguido de anastomose mecânica término-terminal, com grampeador circular, no período de janeiro de 2005 a dezembro de 2007. Neste estudo incluímos mulheres no menacme que se submeteram a tratamento cirúrgico por endometriose profunda infiltrativa com acometimento do reto e sigmoide, atingindo o nível da camada muscular, submucosa ou mucosa. Para o grupo de estudo foram utilizados 24 fragmentos de reto e sigmoide com endometriose confirmada histologicamente, sendo um fragmento de cada uma das 24 pacientes selecionadas. Para o grupo controle, utilizou-se um fragmento da margem distal da ressecção, denominado anel de anastomose, de cada uma das 24 pacientes selecionadas e incluídas no estudo. As amostras foram agrupadas em blocos de Tissue Micro Array (TMA) e submetidas à reação imunoistoquímica para avaliar a expressão do fator de necrose tumoral alfa (TNF-α), do fator de crescimento neural (NGF), do neuropeptídeo Y (NPY) e do peptídeo intestinal vasoativo P (VIP), e posterior análise semiquantitativa da imunomarcação por meio da leitura da densidade ótica relativa (DO). RESULTADOS: Observou-se maior densidade ótica relativa da imunomarcação para TNF-α e NGF no grupo de estudo (amostras com endometriose intestinal), DO= 0,01, respectivamente, para as duas proteínas (p<0,05), em relação aos controles sem endometriose. Não houve diferença estatística na densidade ótica da imunomarcação do NPY e VIP. CONCLUSÃO: Identificou-se o aumento da imunomarcação dos anticorpos TNF-α e NGF em fragmentos de reto e sigmoide comprometidos por endometriose em relação aos controles livres da doença. Não identificamos diferença estatística na imunomarcação das proteínas NPY e VIP.

PURPOSE: To evaluate the expression of neurotrophic (NGF, NPY and VIP) and pro-inflammatory (TNF-α) mediators in the rectum and sigmoid fragments compromised by endometriosis. METHODS: Twenty-four patients were selected to undergo surgical treatment of endometriosis of the rectum and sigmoid colon with a segmental resection technique, followed by end-to-end anastomosis with a circular stapler from January 2005 to December 2007. The study included premenopausal women who underwent surgical treatment for deep endometriosis infiltrating the rectum with involvement of the rectum and sigmoid, reaching the level of the muscle layer, submucosa or mucosa. Twenty-four rectum and sigmoid fragments with histologically confirmed endometriosis, one from each of the 24 selected patients, were used for the study group. For the control group, we used a fragment of the distal resection margin called anastomosis ring from each of the 24 patients enrolled in the study. Samples were grouped into Tissue Micro Array (TMA) blocks and subjected to immunohistochemistry to evaluate the expression of tumor necrosis factor alpha (TNF-α), nerve growth factor (NGF), neuropeptide Y (NPY) and P vasoactive intestinal peptide (VIP), followed by semiquantitative analysis of immunostaining by reading the relative optical density (OD). RESULTS: There was higher optical density relative to TNF-α immunostaining and NGF in the study group (samples with intestinal endometriosis), DO=0.01, for the two proteins, respectively (p<0.05), compared to controls without endometriosis. There was no statistically significant difference in the optical density of immunostaining of NPY and VIP. CONCLUSION: We identified increased immunostaining of TNF-α antibodies and fragments of NGF in the rectum and sigmoid compromised by endometriosis compared to disease-free controls. We did not identify any statistical difference in immunostaining of NPY and VIP proteins.

Eutopic endometrium and peritoneal, ovarian and colorectal endometriotic tissues express a different profile of nectin-1, -3, -4 and nectin-like molecule 2.

STUDY QUESTION: How is the expression of nectins and nectin-like molecules (Necls) detected by immunostaining altered by endometriosis? SUMMARY ANSWER: Our results suggest that Nectin-1, -3, -4 and Necl-2 may contribute to the pathogenesis of endometriosis. Immunostaining of nectins and Necls varies according to the anatomical location of endometriosis. WHAT IS KNOWN AND WHAT THIS PAPER ADDS: Nectin and Necl molecules are immunoglobulin-like cell adhesion molecules involved in apoptosis, cell proliferation and in metastases. Previous studies have demonstrated the involvement of adhesion molecules in the development of endometriotic lesions but no data exist on immunostaining of nectins and Necls molecules in endometriosis. DESIGN, PARTICIPANTS AND SETTING: This retrospective study was conducted in a tertiary-care hospital (Tenon Hospital, Paris, France). Samples were collected from 55 women undergoing endometrial biopsy or surgery for endometriosis and 20 controls having hysterectomy or endometrial biopsy for other reasons; multiple samples were collected from 15 women. We studied the immunostaining of Nectin-1, -3, -4 and Necl-2 in secretory and proliferative endometrium from women with (n = 20) or without endometriosis (i.e. control group, n = 20), and in peritoneal (n = 20), ovarian (n = 20) and colorectal endometriosis (n = 20). MAIN RESULTS: Semi-quantitative immunostaining demonstrated that (1) Necl-2 staining was stronger in all types of endometriotic lesions than in the eutopic endometrium from patients with endometriosis (P < 0.0125) and in ovarian endometriotic cysts compared with other locations (P < 0.001); (2) Nectin-3 staining was stronger in the eutopic endometrium of patients with endometriosis compared with controls (P = 0.03) and in all endometriotic lesions compared with the eutopic endometrium from patients with endometriosis (P < 0.0125); (3) Nectin-4, staining was stronger in the eutopic endometrium of patients with endometriosis compared with controls (P = 0.04) and (4) Nectin-1 staining was significantly increased in colorectal endometriosis compared with other locations (P = 0.004). BIAS, CONFOUNDING AND OTHER REASONS FOR CAUTION: We did not assess the pattern of expression in endometriosis of all nectins and Necl molecules. Indeed, Necl-5 is implicated in many pathophysiological processes such as cell movement and proliferation with potential relevance to endometriosis. GENERALISABILITY TO OTHER POPULATIONS: At present, few data on implication of nectins and Necl molecules in endometriosis exist. Hence, our results should be confirmed by further quantitative studies at protein or RNA levels. STUDY FUNDING/COMPETING INTEREST(S): No funding source. All the authors declare no conflict of interest.

[Expression of neurotrophic and inflammatory mediators in rectosigmoid endometriosis]. / Expressão de mediadores neurotróficos e pró-inflamatórios na endometriose de reto e sigmoide.

PURPOSE: To evaluate the expression of neurotrophic (NGF, NPY and VIP) and pro-inflammatory (TNF-α) mediators in the rectum and sigmoid fragments compromised by endometriosis. METHODS: Twenty-four patients were selected to undergo surgical treatment of endometriosis of the rectum and sigmoid colon with a segmental resection technique, followed by end-to-end anastomosis with a circular stapler from January 2005 to December 2007. The study included premenopausal women who underwent surgical treatment for deep endometriosis infiltrating the rectum with involvement of the rectum and sigmoid, reaching the level of the muscle layer, submucosa or mucosa. Twenty-four rectum and sigmoid fragments with histologically confirmed endometriosis, one from each of the 24 selected patients, were used for the study group. For the control group, we used a fragment of the distal resection margin called anastomosis ring from each of the 24 patients enrolled in the study. Samples were grouped into Tissue Micro Array (TMA) blocks and subjected to immunohistochemistry to evaluate the expression of tumor necrosis factor alpha (TNF-α), nerve growth factor (NGF), neuropeptide Y (NPY) and P vasoactive intestinal peptide (VIP), followed by semiquantitative analysis of immunostaining by reading the relative optical density (OD). RESULTS: There was higher optical density relative to TNF-α immunostaining and NGF in the study group (samples with intestinal endometriosis), DO=0.01, for the two proteins, respectively (p<0.05), compared to controls without endometriosis. There was no statistically significant difference in the optical density of immunostaining of NPY and VIP. CONCLUSION: We identified increased immunostaining of TNF-α antibodies and fragments of NGF in the rectum and sigmoid compromised by endometriosis compared to disease-free controls. We did not identify any statistical difference in immunostaining of NPY and VIP proteins.

Ectopic gastric mucosa and pancreatic ducts in the rectum.

A 68-year-old woman with fecal occult blood was referred to Dokkyo Medical School Hospital. Colonoscopy demonstrated a flat lesion in the rectum, and endoscopic mucosal resection of the lesion was performed. Histologic examination revealed that it contained ectopic gastric mucosa, which had a gastric foveolar and glandular mucinous phenotype, as demonstrated by immunohistochemistry. Moreover, the lesion also contained CA19-9- and CK7-positive pancreatic duct-like components in the submucosal layer. The present case is the first report to describe ectopic gastric mucosa and pancreatic ducts concurrently arising in the rectum.

Randomized controlled trial of preoperative oral carbohydrate treatment in major abdominal surgery.

BACKGROUND: Major surgery is associated with postoperative insulin resistance which is attenuated by preoperative carbohydrate (CHO) treatment. The effect of this treatment on clinical outcome after major abdominal surgery has not been assessed in a double-blind randomized trial. METHODS: Patients undergoing elective colorectal surgery or liver resection were randomized to oral CHO or placebo drinks to be taken on the evening before surgery and 2 h before induction of anaesthesia. Primary outcomes were postoperative length of hospital stay and fatigue measured by visual analogue scale. RESULTS: Sixty-nine and 73 patients were evaluated in the CHO and placebo groups respectively. The groups were well matched with respect to surgical procedure, epidural analgesia, laparoscopic procedures, fasting period before induction and duration of surgery. Postoperative changes in fatigue score from baseline did not differ between the groups. Median (range) hospital stay was 7 (2-35) days in the CHO group and 8 (2-92) days in the placebo group (P = 0.344). For patients not receiving epidural blockade or laparoscopic surgery (20 CHO, 19 placebo), values were 7 (3-11) and 9 (2-48) days respectively (P = 0.054). CONCLUSION: Preoperative CHO treatment did not improve postoperative fatigue or length of hospital stay after major abdominal surgery. A benefit is not ruled out when epidural blockade or laparoscopic procedures are not used. REGISTRATION NUMBER: ACTRN012605000456651 (http://www.anzctr.org.au).

Immunohistochemical evaluation of endometriotic lesions and disseminated endometriosis-like cells in incidental lymph nodes of patients with endometriosis.

OBJECTIVE: To investigate the frequency of endometriotic lesions and disseminated endometriotic-like cells in a series of incidentally removed lymph nodes (LNs) in patients with endometriosis. DESIGN: Retrospective study. SETTING: University hospital endometriosis center. PATIENT(S): Premenopausal patients underwent surgery because of endometriosis-associated symptoms. INTERVENTION(S): Retrospective analysis of 108 coincidentally resected LNs of 24 patients with endometriosis. To identify endometriotic cells, immunohistochemical analysis of estrogen and progestogen receptor (ER-PR), CD10, and cytokeratin was performed. MEAN OUTCOME MEASURE(S): The occurrence of endometriotic lesions (ER-PR, CD10, and cytokeratin positive) and disseminated endometriotic-like ER-PR-positive cells in LNs. RESULT(S): Deep infiltrating endometriosis was diagnosed in 23 of the 24 patients with incidentally removed LNs. In 8 of 24 (33.3%) patients with incidentally removed LNs, typical endometriotic lesions were detected. Disseminated ER-PR-positive cells were found in 17 of 24 patients (70.8%). Lymph node involvement correlated directly with the deep infiltrating endometriosis lesional size. CONCLUSION(S): Estrogen receptor-progestogen receptor-positive endometriotic lesions and disseminated endometriotic-like cells frequently are detected in LNs of patients with deep infiltrating endometriosis and, therefore, might reflect "nonlocalized" disease. If clinical significance of such lesions were provided, adjuvant hormonal treatment could be considered as a possible additional mode of therapy.

Solitary rectal ulcer syndrome: a clinicopathological study of 13 cases.

BACKGROUND/AIMS: Solitary rectal ulcer syndrome (SRUS) is a rare disorder that has a wide spectrum of clinical presentation and variable endoscopic findings. To further characterize the clinical and pathological features, a retrospective, hospital-based clinicopathological study was conducted. MATERIALS AND METHODS: All cases of SRUS diagnosed at Farwania Hospital, Kuwait, between 2002 and 2007 were retrieved from the computerized filing system. The histological slides were reviewed by two authors to confirm the diagnosis. Immunohistochemical stain for smooth muscle actin (SMA) was performed. The clinical files were reviewed for clinical features and endoscopic findings. RESULTS: Thirteen cases were identified: 8 males and 5 females. The age range was 15-85. Rectal bleeding, constipation, and abdominal pain were the most common presenting symptoms and were seen, either alone or in various combinations, in 12 of the 13 cases. Rectal ulceration was the most common endoscopic finding, being seen in 9 of the 3 cases; 3 of these cases had multiple ulcerations. Two patients had rectal polyps, with one of them having multiple polyps. The histological examination revealed surface serration, fibromuscular obliteration of the lamina propria, and crypts' distortion in all the cases. Seven of the cases had diamond crypts. Ectatic mucosal vessels were a common finding. Positivity for SMA in the lamina propria was seen in all examined cases. CONCLUSION: SRUS is a rare disorder and only 13 cases were diagnosed in Farwania hospital over a 6-year period. The clinical presentation of our patients was variable. The presence of polyps and multiple ulcerations on endoscopy is further evidence that SRUS is a misnomer. Surface serration, fibromuscular obliteration, and crypts' distortion are the most characteristic features. The presence of diamond crypts is an additional diagnostic feature.

Status of HER1 and HER2 in peritoneal, ovarian and colorectal endometriosis and ovarian endometrioid adenocarcinoma.

A role for the EGF system, in particular HER1 and 2, in growth of the endometrium has been suggested but HER1 and 2 have not been studied in all locations of endometriosis and in ovarian endometrioid adenocarcinoma (OEC) which is a rare form of malignant transformation of endometriosis. Immunohistochemistry (IHC) was used for studying HER1 and HER2 in ovarian (n = 10), peritoneal (n = 10), colorectal endometriosis (n = 20) and OEC (n = 10). Fluorescent in situ hybridisation (FISH) was used for analysing the status of HER2 gene in colorectal endometriosis and OEC. All samples were negative for HER2 in both glandular and stromal cells and in glandular cells for HER1 by IHC. In 15 out of 20 colorectal endometriosis, there was a weak expression in stromal cells. Following FISH, two colorectal samples had a partial 17 aneusomy and three OEC, a 17 polysomy. The other samples were 17 disomic without HER2 amplification; HER1 and 2 do not seem to have a role in endometriosis physiopathology.

Estrogen and progestogen receptor positive endometriotic lesions and disseminated cells in pelvic sentinel lymph nodes of patients with deep infiltrating rectovaginal endometriosis: a pilot study.

BACKGROUND: Deep infiltrating endometriosis (DIE) shows similarities to malignant diseases. A recent study involving DIE patients found endometriosis in mesorectal lymph nodes (LNs) after segmental bowel resection. However, it is unclear whether this observation is a local phenomenon or a sign of systemic disease. Therefore, we conducted a prospective study to investigate the occurrence of endometriosis in pelvic sentinel lymph nodes (SLNs) in patients with DIE. METHODS: Fourteen patients underwent primary surgery for symptomatic DIE. Combined vaginal laparoscopic-assisted resection of the rectovaginal septum was performed. Dye was injected into the visible/palpable nodule. SLNs were removed from the iliac region. In order to identify endometriotic cells, immunohistochemical analysis of estrogen and progestogen receptors, CD10 and cytokeratin was performed. RESULTS: In 12 out of 14 patients with DIE, SLNs were detected. The localization of the SLN followed the typical LN spread of the upper vagina. In three patients, we could detect typical endometriotic lesions in the LNs. Ten out of 12 (83.3%) SLNs showed disseminated estrogen and/or progestogen positive cells. CONCLUSIONS: By using immunohistochemistry, we could demonstrate endometriotic lesions and endometriotic-like cells in pelvic SLNs of patients with DIE suggesting the potential for lymphatic spread of the disease.