The Outcomes of Endoanal Ultrasound and Three-Dimensional, High-Resolution Anorectal Manometry do not Predict Fecal Incontinence

Endoanal ultrasound (EUS) is the gold standard for diagnosing anal sphincter defects often seen in patients with fecal incontinence (FI). Threedimensional, high-resolution anorectal manometry (3D-HRARM) is a newer technique that might also be used to diagnose sphincter defects. We aimed to investigate whether FI is associated with anal sphincter defects detected by EUS and 3D-HRARM. Retrospectively, we included all adult patients who had undergone EUS and 3D-HRARM for FI, between January 2012 and February 2015 (N = 37). During 3D-HRARM, the presence of sphincter defects was examined in rest and during maximal anal sphincter contraction. All patients also underwent a balloon retention test to objectively determine whether they suffered from FI for solid stool. Of the 37 patients, 12 patients (32%) suffered from FI. The presence of a sphincter defect detected with EUS, and with 3D-HRARM during contraction, was not associated with the prevalence of FI and no significant correlations were found between these variables. The presence of a sphincter defect, detected by 3D-HRARM in rest, was negatively correlated with the presence of FI (rs -.372, P = .024). Moreover, the prevalence of sphincter defects was lower in patients with FI, detected by 3D-HRARM in rest, than in patients without FI (13% versus 88%, P = .035). FI is not associated with anal sphincter defects detected by EUS and 3D-HRARM. The outcomes of EUS and 3D-HRARM do not thus predict the presence of FI. Instead, extensive anorectal function tests should be performed to form a complete picture of a patient’s anorectal functions and to determine the underlying causes of FI

Measurement of distal intramural spread and the optimal distal resection by naked eyes after neoadjuvant radiation for rectal cancers

BACKGROUND: The safe distance between the intraoperative resection line and the visible margin of the distal rectal tumor after preoperative radiotherapy is unclear. We aimed to investigate the furthest tumor intramural spread distance in fresh tissue to determine a safe distal intraoperative resection margin length. METHODS: Twenty rectal cancer specimens were collected after preoperative radiotherapy. Tumor intramural spread distances were defined as the distance between the tumor’s visible and microscopic margins. Visible tumor margins in fresh specimens were identified during the operation and were labeled with 5 - 0 sutures under the naked eye at the distal 5, 6, and 7 o’clock directions of visible margins immediately after removal of the tumor. After fixation with formalin, the sutures were injected with nanocarbon particles. Longitudinal tissues were collected along three labels and stained with hematoxylin and eosin. The spread distance after formalin fixation was measured between the furthest intramural spread of tumor cells and the nanocarbon under a microscope. A positive intramural spread distance indicated that the furthest tumor cell was distal to the nanocarbon, and a negative value indicated that the tumor cell was proximal to the nanocarbon. The tumor intramural spread distance in fresh tissue during the operation was 1.75 times the tumor intramural spread distance after formalin fixation according to the literature. RESULTS: At the distal 5, 6, and 7 o’clock direction, seven (35%), five (25%), and six (30%) patients, respectively, had distal tumor cell intramural spread distance > 0 mm. The mean and 95% confidence interval of tumor cell intramural spread distance in fresh tissue during operation was − 0.3 (95%CI − 4.0 ~ 3.4) mm, − 0.9 (95%CI − 3.4 ~ 1.7) mm, and − 0.4 (95%CI − 3.5 ~ 2.8) mm, respectively. The maximal intraoperative intramural spread distances in fresh tissue were 8.8, 7, and 7 mm, respectively. CONCLUSIONS: The intraoperative distance between the distal resection line and the visible margin of the rectal tumor after radiotherapy should not be less than 1 cm to ensure oncological safety

Physiological mechanisms underlying fecal continence

Abstract The machinery maintaining fecal continence prevents involuntary loss of stool and is based on synchronized interplay of multiple voluntary and involuntary mechanisms, dependent on cooperation between motor responses of the musculature of the colon, pelvic floor and anorectum, and on sensory and motor neural pathways. Knowledge of the physiology of fecal continence is key towards understanding the pathophysiology of fecal incontinence. The idea that involuntary contraction of the internal anal sphincter is the primary mechanism of continence and that external anal sphincter supports continence only by voluntary contraction is outdated. Other mechanisms have come to the forefront and they have significantelly changed viewpoints on the mechanisms of continence and incontinence. And so for instance, involuntary contractions of the external anal sphincter, the puborectal muscle and the sphincter of O'Beirne have been proven to play a role in fecal continence. Also, retrograde propagating cyclic motor patterns in the sigmoid and rectum promote retrograde transit to prevent continuous flow of content into the anal canal. With this review we aim to give an overview of primary and secondary mechanisms controlling fecal continence and evaluate the strenght of evidence

Physiological mechanisms underlying fecal continence

Abstract The machinery maintaining fecal continence prevents involuntary loss of stool and is based on synchronized interplay of multiple voluntary and involuntary mechanisms, dependent on cooperation between motor responses of the musculature of the colon, pelvic floor and anorectum, and on sensory and motor neural pathways. Knowledge of the physiology of fecal continence is key towards understanding the pathophysiology of fecal incontinence. The idea that involuntary contraction of the internal anal sphincter is the primary mechanism of continence and that external anal sphincter supports continence only by voluntary contraction is outdated. Other mechanisms have come to the forefront and they have significantelly changed viewpoints on the mechanisms of continence and incontinence. And so for instance, involuntary contractions of the external anal sphincter, the puborectal muscle and the sphincter of O'Beirne have been proven to play a role in fecal continence. Also, retrograde propagating cyclic motor patterns in the sigmoid and rectum promote retrograde transit to prevent continuous flow of content into the anal canal. With this review we aim to give an overview of primary and secondary mechanisms controlling fecal continence and evaluate the strenght of evidence

EpCAM in morphogenesis

Embryonic development is one of the most complex biological phenomena that involves the appropriate expression and synchronized interactions of a plethora of proteins, including cell adhesion molecules (CAMs). Many members of the diverse family of CAMs have been shown to be critically involved in the correct execution of embryonic development. The Epithelial Cell Adhesion Molecule (EpCAM) is an atypical cell adhesion molecule originally identified as a marker for carcinoma. However, recent insights have revealed that EpCAM participates in not only cell adhesion, but also in proliferation, migration and differentiation of cells. All of these processes are known to be fundamental for morphogenesis. Here, we review the current literature that establishes EpCAM as a protein involved in morphogenesis, starting from the earliest stages of embryogenesis and ending in organogenesis. In addition, we provide directions for further elucidation of the role of EpCAM in embryogenesis

EpCAM homologues exhibit epithelial-specific but different expression patterns in the kidney

The Epithelial Cell Adhesion Molecule (EpCAM) is expressed virtually on normal epithelia in vertebrates. Among different species, the amino acid sequence of EpCAM is highly homologous, indicating that EpCAM is an evolutionary conserved protein. However, differences in the expression pattern of EpCAM homologues have been reported. We hypothesized that differences in expression pattern might be related to the promoter organization of the respective EpCAM homologues. Therefore, we here compared the promoter region of the mouse and human EpCAM homologues. In addition, we compared the expression pattern of the human and murine EpCAM homologues in the hEpCAM transgenic mouse. In silico analysis of EpCAM homologues revealed that the amino acid sequence as well as the domain structure is highly conserved throughout different vertebrates. In silico analysis of the promoter region identified that the human and mouse EpCAM promoters share a low homology. In agreement with this low homology, the murine and human EpCAM promoter contains only a few common transcription factor binding sites. Nevertheless, immunohistochemcial analysis of the expression of human and murine EpCAM in lung, colon, and kidney of the hEpCAM transgenic mouse identified that expression of both homologues is restricted to epithelial cells in these organs. Moreover, in lung and colon the human and murine homologues of EpCAM were co-expressed. In contrast, the EpCAM homologues were only sporadically co-expressed in renal epithelia, although they were distributed similarly along the nephronic segments. Together, these findings indicate an overall conserved regulatory mechanism that ensures epithelial expression of EpCAM homologues, despite the low promoter homology. Furthermore, the fact that murine epithelia express the human homologue of EpCAM indicates that the mouse has transcription factors required for human EpCAM expression