A novel age-related venous amyloidosis derived from EGF-containing fibulin-like extracellular matrix protein 1.

Most intractable tissue-degenerative disorders share a common pathogenic condition, so-called proteinopathy. Amyloid-related disorders are the most common proteinopathies and are characterized by amyloid fibril deposits in the brain or other organs. Aging is generally associated with the development of these amyloid-related disorders, but we still do not fully understand how functional proteins become pathogenic amyloid deposits during the human aging process. We identified a novel amyloidogenic protein, named epidermal growth factor-containing fibulin-like extracellular matrix protein 1 (EFEMP1), in massive venous amyloid deposits in specimens that we obtained from an autopsied patient who died of gastrointestinal bleeding. Our postmortem analyses of additional patients indicate that EFEMP1 amyloid deposits frequently developed in systemic venous walls of elderly people. EFEMP1 was highly expressed in veins, and aging enhanced venous EFEMP1 expression. In addition, biochemical analyses indicated that these venous amyloid deposits consisted of C-terminal regions of EFEMP1. In vitro studies showed that C-terminal regions formed amyloid fibrils, which inhibited venous tube formation and cell viability. EFEMP1 thus caused a novel age-related venous amyloid-related disorder frequently found in the elderly population. Understanding EFEMP1 amyloid formation provides new insights into amyloid-related disorders occurring during the aging process. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

A three-dimensional computed tomography angiography study of the anatomy of the accessory middle colic artery and implications for colorectal cancer surgery.

PURPOSE: In the present study, we focused on the accessory middle colic artery and aimed to increase the safety and curative value of colorectal cancer surgery by investigating the artery course and branching patterns. METHODS: We included 143 cases (mean age, 70.4 ± 11.2 years; 86 males) that had undergone surgery for neoplastic large intestinal lesions at the First Department of Surgery at Yamagata University Hospital between August 2015 and July 2018. We constructed three-dimensional (3D) computed tomography (CT) angiograms and fused them with reconstructions of the large intestines. We investigated the prevalence of the accessory middle colic artery, the variability of its origin, and the prevalence and anatomy of the arteries accompanying the inferior mesenteric vein at the same level as the origin of the inferior mesenteric artery. RESULTS: Accessory middle colic artery was observed in 48.9% (70/143) cases. This arose from the superior mesenteric artery in 47, from the inferior mesenteric artery in 21, and from the celiac artery in two cases. In 78.2% (112/143) cases, an artery accompanying the inferior mesenteric vein was present at the same level as the origin of the inferior mesenteric artery; this artery was the left colic artery in 92, the accessory middle colic artery in 11, and it divided and became the left colic artery and the accessory middle colic artery in 10 cases. CONCLUSION: 3D CT angiograms are useful for preoperative evaluation. Accessory middle colic arteries exist and were observed in 14.9% of cases.

Near-Infrared Indocyanine Green-Enhanced Fluorescence and Evaluation of the Bowel Microperfusion During Robotic Colorectal Surgery: a Retrospective Original Paper.

BACKGROUND: Leakage of the anastomosis after colorectal surgery is a severe complication, and one of the most important causes is poor vascular supply. However, a microvascular deficit is often not detectable during surgery under white light. Near-infrared indocyanine green (ICG)-enhanced fluorescence may be useful for assessing microvascular deficits and conceivably preventing anastomotic leakage. OBJECTIVES: This paper presents a preliminary retrospective case series on robotic colorectal surgery. The aim is to evaluate the feasibility, safety and role of near-infrared ICG-enhanced ?uorescence for the intraoperative assessment of peri-anastomotic tissue vascular perfusion. MATERIALS AND METHODS: From among more than 164 robotic colorectal cases performed, we retrospectively analyzed 28 that were all performed by the same surgeon (PCG) using near-infrared ICG-enhanced fluorescence technology: 16 left colectomies (57.1%), 8 rectal resections (28.6%), 3 right colectomies (10.8%) and 1 pancolectomy (3.6%). RESULTS: The rates of conversion, intraoperative complications, dye allergic reaction and mortality were all 0%. In two cases (7.1%)-1 left and 1 right colectomy-the level of the anastomosis was changed intraoperatively after ICG showed ischemic tissues. Despite the application of ICG, one anastomotic leak (after left colectomy for a chronic recurrent sigmoid diverticulitis with pericolic abscess) was observed. CONCLUSIONS: ICG technology may help to determine when to intraoperatively change the anastomotic level to a safer location. In our case series, ICG results led to a change in the level of the anastomosis in 7.1% of the cases. Despite the use of ICG, we observed one leak. This may have been related to vascularization-independent causes (e.g., infection in this case) or may reflect a need for better standardization of this ICG technology. In particular, we need a way to objectively assess the ICG signal and the related risk of leakage. More randomized, prospective, well-powered trials are needed to unveil the full potential of this innovative surgical technology.

Dual-Energy CT Iodine Mapping and 40-keV Monoenergetic Applications in the Diagnosis of Acute Bowel Ischemia.

OBJECTIVE: Sensitivity of CT of the abdomen for detection of acute bowel ischemia (ABI) can be as low as 60%. In this study, we assessed the diagnostic performance of iodine-map and monoenergetic (40-keV) images in patients with suspected ABI. MATERIALS AND METHODS: This retrospective study included 60 consecutive patients with suspected ABI who underwent a standardized imaging protocol dual-source dual-energy CT (DECT) over a 26-month period. Clinical and operative outcomes were recorded as the reference standard. Two abdominal radiologists who were unaware of clinical and surgical information independently assessed conventional CT images for ABI. After a time interval designed to reduce recall, readers reassessed conventional images with supplementary iodine-map and 40-keV postprocessed images. Quantitative ROI analysis was also performed. RESULTS: ABI was observed in 11 patients. For reader A, sensitivity was 63.6% (95% CI, 30.8-89.1%) when interpreting conventional images alone. Sensitivity for detection of ABI increased to 81.8% (95% CI, 48.2-97.7%) and 100% (95% CI, 71.5-100%) when iodine-map and 40-keV images were assessed, respectively. For reader B, no change in sensitivity was seen with either technique, but the number of false-positives were reduced with supplementary iodine-map and 40-keV postprocessed images. Interobserver agreement was fair with conventional images (κ = 0.29) but improved to moderate (κ = 0.45) and substantial (κ = 0.63) with iodine-map and 40-keV images, respectively. Quantitative assessment found significant differences in iodine uptake (1.01 ± 0.55 mg/mL vs 3.04 ± 1.19 mg/mL) and mean attenuation (75.2 ± 38.4 HU vs 163.5 ± 48.9 HU) between nonischemic and ischemic segments, respectively. CONCLUSION: Iodine-map and 40-keV monoenergetic images increase conspicuity of ABI, resulting in improved diagnostic accuracy compared with review of conventional CT images alone.

[Pathomorphological peculiarities of hemomicrocirculatory bed of the small and large intestine in acute peritonitis].

Experimental comparative morphological investigation of hemomicrocirculation bed (HMCB) of the small and large bowel wall was performed in dynamics of an acute serous peritonitis. Spreaded aseptic peritonitis was simulated using injection of 5 ml of gamma-caraginen (Sigma, USA) in 1 ml of isotonic solution of sodium chloride. On the early stage of peritonitis (in 12 h from beginning of the experiment) in mucosa of small bowel nonsignificant venuls dilatation and the capillary lumen reduction were observed. In 1 day (reactive stage of peritonitis) in mucosa the quantity of capillars have had reduced significantly, comparing with such observed previously. On the 2-nd day (toxic stage of peritonitis) some capillary dilatation in intestinal villi and crypts coexistant with the blood rheology disorders in a form of stasis, change in permeability of the vessels walls, predominantly of the venous, was noted. On the 3-d day (late stage) the arteriol's spasm have had reduced, capillary paralytic dilatation was revealed. The staged course of experimental peritonitis with the HMCB changes, characteristic for every stage, was confirmed, basing on analysis of the investigation result.

Distribution of arterial supply to the large intestine in the anteater (Tamandua tetradactyla).

The blood supply in the large intestine of seven specimens of the lesser anteater, Tamandua tetradactyla, studied. The method included preparation of the macroscopic collection report, perfusion of the arterial network with water, injection of colored latex, fixation in formaldehyde, and preservation in ethanol. For our description and analyses, we performed dissections under mesoscopic light and made photo documentation of our observations. The large intestine of T. tetradactyla is irrigated by the caudal mesenteric artery (rectum, left colic fold, descending colon and transverse colon) and cranial mesenteric artery (right colic fold, cecal pouch). We observed that the large intestine in these animals is implied in the abdominal wall without becoming affixed to the wall, or developing adhesions on individual segments. The caudal mesenteric artery feeds the straight collateral branches (primary, secondary, and tertiary) and a few juxtacolic arched branches (first and second order). The straight branches emerge from the arched branches, bifurcate, and embrace the intestinal loop to irrigate it. The presence of anastomoses between the CaMA and the CrMA apparently ensures a relatively stable flow in the event of failure of either. This is very important, as the peritoneum in this species is completely dependent on blood from these two arteries. The model of vascularization and fixation of the large intestine into the abdominal wall of T. tetradactyla is different from that in other vertebrates.

Atherosclerotic inferior mesenteric artery stenosis resulting in large intestinal hypoperfusion: a paradigm shift in the diagnosis and management of symptomatic chronic mesenteric ischemia.

Symptomatic chronic mesenteric ischemia results from intestinal hypoperfusion and is classically thought to result from involvement of two or more mesenteric arteries. The celiac artery and superior mesenteric artery are most frequently implicated in this disease process, and their involvement usually results in symptoms of small intestinal ischemia. Symptomatic chronic mesenteric ischemia resulting predominantly from inferior mesenteric artery involvement has largely been overlooked but does gives rise to its own, unique clinical presentation with symptoms resulting from large intestinal ischemia. We present four patients with atherosclerotic inferior mesenteric artery stenosis with symptomatic chronic mesenteric ischemia that have unique clinical presentations consistent with large intestinal ischemia that resolved following percutaneous endovascular treatment of the inferior mesenteric artery stenosis. These cases represent a novel approach to the diagnosis and management of this disease process and may warrant a further subclassification of chronic mesenteric ischemia into chronic small intestinal ischemia and chronic large intestinal ischemia.

A somatostatin analogue, octreotide, ameliorates intestinal ischemia-reperfusion injury through the early induction of heme oxygenase-1.

BACKGROUND: Intestinal damage after ischemia followed by revascularization, referred to as "ischemia-reperfusion (I/R) injury," is a devastating complication that can occur after acute superior mesenteric obstruction, or after both elective and emergent abdominal aortic surgery. Once an entire layer of intestine is involved in severe ischemia, the mortality rate reaches 90%; no effective medical treatment has been reported to date. Here, we demonstrate that a somatostatin analogue, octreotide, but not a free-radical scavenger, MCI-186, prevented death due to surgically induced intestinal I/R injury in rats. METHODS: Superior mesenteric artery (SMA) of Male Sprague-Dawley rats, that received MCI-186 or octreotide, was surgically clamped, and then the clips were removed and SMA blood flow restored. Survival was assessed, and blood and small intestine were subjected to cell count, enzyme-linked immunosorbent assay (ELISA), Western blotting, and immunohistochemistry. RESULTS: Of interest, pretreatment with octreotide, but not with MCI-186, just before induced intestinal ischemia prompted the early expression of heme oxygenase-1 (HO-1) protein-associated accumulation of CD68-positive cells, a possible cellular source of HO-1. Inversely, the administration of tin protoporphyrin IX (SnPPN), a specific inhibitor of HO-1, completely abolished the therapeutic effects of octreotide, indicating that the favorable effects of octreotide against intestinal I/R injury is predominantly dependent on the early induction of HO-1. CONCLUSIONS: These results suggest that a somatostatin analogue may be useful in leading to an improvement of the prognosis of patients with intestinal I/R injury in the clinical setting.

Intraoperative contrast-enhanced sonography of bowel blood flow: preliminary experience.

OBJECTIVES: The potential to predict, and therefore avoid, anastomotic failure has eluded generations of colon and rectal surgeons to date. A reliable, reproducible method of assessing bowel blood flow therefore would be of enormous potential clinical relevance. To our knowledge, intraoperative contrast-enhanced sonography of the bowel has not been performed previously. We present our study assessing the feasibility of using contrast-enhanced sonography to study bowel perfusion intraoperatively. METHODS: We studied 8 patients (4 male and 4 female) with an age range of 52 to 81 years who underwent colorectal surgery (right hemicolectomies, n = 3; Hartmann procedure, n = 1; anterior resections, n = 2; and bowel resections with ileocolic anastomoses, n = 2). A 5-mL bolus of a sulfur hexafluoride contrast agent solution was injected before and after vascular ligation with simultaneous noncompression ultrasound scanning directly over the large bowel. The patients were followed clinically to assess for leaks. Contrast-enhanced sonographic time-intensity curves were generated for the time to peak and maximum amplitude. RESULTS: Moderate interobserver agreement was shown for the time to peak (κ = 0.50) and maximum amplitude (κ = 0.42), and moderate intraobserver agreement was shown for the time to peak (κ= 0.53) and maximum amplitude (κ= 0.53). No significant differences were shown between the time to peak (P = .28) and maximum amplitude (P = .49) for the preligation and postligation scans. CONCLUSIONS: To our knowledge, intraoperative contrast-enhanced sonography of the bowel has not been performed previously. We have shown the technique to be feasible with good intraobserver and interobserver agreement. Further work is ongoing to optimize the technique and assess its use in predicting anastomotic breakdown.

[The risk factors of the sutures insufficiency and the choice of the anastomosis formation method during reconstruction-restoration operations on the large bowel].

Basing on statistical analysis of 17 prognostic risk factors for occurrence of the sutures insufficiency in a large bowel anastomoses (SILBA) in 237 patients there was established a trustworthy correlational connection for 7 factors. The results of a regression analysis have had confirmed the influence of the anastomosis formation method on the complication rate, demonstrated by an active inflammation in the anastomosis formation area, technical faults while the wall mobilization and rude formation of sutures, intramural disorder of the blood circulation, the blood circulation general disorders, local infectioning and hypoproteinemia. Application of analysis of the tables of conjunction and comparison in accordance with the numeral and interval predictors, using nonparametric analysis (the method of a binary logistic regression), have permitted to delineate the most prognostically significant risk factors of the SILBA occurrence.

An in vivo investigation of photoplethysmographic signals and preliminary pulse oximetry estimation from the bowel using a new fiberoptic sensor.

BACKGROUND: The continuous monitoring of splanchnic organ oxygen saturation could make the early detection of inadequate tissue oxygenation feasible, reducing the risk of hypoperfusion, severe ischemia, multiple organ failure, and, ultimately, death. Current methods for assessing splanchnic perfusion have not been widely accepted for use in the clinical care environment. In an attempt to overcome the limitations of the current techniques, a new fiberoptic photoplethysmographic (PPG)/pulse oximetry sensor was developed as a means of assessing splanchnic organ perfusion during surgery in humans. METHODS: A new fiberoptic splanchnic pulse oximeter and an optically identical fiberoptic finger pulse oximeter have been developed. Simultaneous PPG signals and preliminary estimates of arterial oxygen saturation from the bowel (small and large) and finger were obtained in 17 patients (3 men and 14 women) undergoing open laparotomy. RESULTS: Good quality PPG signals were obtained from the small and large bowel and from the finger in all patients (lower 95% confidence limit for the proportion was 0.64). Comparisons of blood oxygen saturation values acquired when using the splanchnic and the finger fiberoptic sensors and a commercial finger pulse oximeter indicated that there was no statistically significant difference between them (all P>0.454). A Bland and Altman plot of the difference between blood oxygen saturation values from the bowel fiberoptic pulse oximeter and the fiberoptic finger pulse oximeter against their mean showed that the limits of agreement between the 2 pulse oximeters were -3.8% and 4.2% for small bowel measurements, and -3.4% and 4.3% for large bowel measurements. The 95% prediction interval for the difference between the 2 devices was between -4.2% and 4.7%. CONCLUSION: This study demonstrated that good quality PPG signals can be obtained from the bowel using a new fiberoptic sensor. Further evaluation is required to determine whether fiberoptic pulse oximetry of the bowel may provide a suitable method for monitoring splanchnic perfusion.

The spatial arrangement of the human large intestinal wall blood circulation.

The aim of the study was to describe and depict the spatial arrangement of the colon microcirculatory bed as a whole. Various parts of the large intestine and terminal ileum were harvested from either cadaver or section material or gained peroperatively. Samples were then injected with India ink or methylmetacrylate Mercox resin for microdissection and corrosion casting for scanning electron microscopy. The results showed that extramural vasa recta ramified to form the subserous plexus, some of them passing underneath the colon taeniae. Branches of both short and long vasa recta merged in the colon wall, pierced the muscular layer and spread out as the submucous plexus, which extended throughout the whole intestine without any interruption. The muscular layer received blood via both the centrifugal branches of the submucous plexus and the minor branches sent off by the subserous plexus. The mucosa was supplied by the mucous plexus, which sent capillaries into the walls of intestinal glands. The hexagonal arrangement of the intestinal glands reflected their vascular bed. All three presumptive critical points are only gross anatomical points of no physiological relevance in healthy individuals. Neither microscopic weak points nor regional differences were proven within the wall of the whole large intestine. The corrosion casts showed a huge density of capillaries under the mucosa of the large intestine. A regular hexagonal pattern of the vascular bed on the inner surface was revealed. No microvascular critical point proofs were confirmed and a correlation model to various pathological states was created.

Microvascular anatomy of the large intestine in adult Xenopus laevis: scanning electron microscopy of vascular corrosion casts and correlative light microscopy.

The microvascular anatomy of the large intestine of the adult South African Clawed Toad, Xenopus laevis (Daudin), was studied by scanning electron microscopy (SEM) of vascular corrosion casts (VCCs) and correlative light microscopy. Observations showed the large intestine to be supplied by the haemorrhoidal artery and the posterior mesenteric artery and drain via the posterior haemorrhoidal vein into either the left or right posterior abdominal vein. Both arteries and veins showed a bipinnate supply/draining pattern with branches running circumferentially. Vessels embraced the gut wall while arteries and veins in most cases alternated along the gut length. Many short terminal arterioles arose from the circumferential arteries at almost acute angles and capillarized after a short distance. Capillary lengths were short and continued into numerous postcapillary venules which merged either in a leaf vein-like formation or in a rosette-like formation with up to four draining sites per supplying arteriole. The microvasculature was found to be well adapted 1) to sustain blood flow under different amounts of feces in the gut and 2) to provide optimal conditions for the resorption of water and salts from the gut lumen into the blood vascular system by the high number of venules and their conspiciouos rosette-like and leaf vein-like patterns.

Effects of cyclooxygenase inhibition on anastomotic healing following large bowel resection in a rabbit model--a randomized, blinded, placebo-controlled trial.

PURPOSE: We performed an experimental study in a rabbit model to investigate the effects of a selective Cox-2 inhibitor (Valdecoxib) on anastomotic healing following large bowel resection after 1 week. MATERIALS AND METHODS: Eighty New Zealand white rabbits were randomized into four groups and underwent a colon resection with end-to-end anastomosis. Group 1 (n = 20) was treated with Valdecoxib, group 2 with Metamizole (Novalgin), group 3 with Resveratrol (specific Cox-1 inhibitor), or a placebo vehicle with similar volume (group 4). Anastomotic healing was tested at the seventh postoperative day by measurement of the bursting pressure in vitro. Immunohistochemical staining of the anastomotic site was performed with polyclonal antibodies (CD31). RESULTS: There were no significant differences in anastomotic dehiscence, bursting pressure, or vessel density between the treatment and control groups. CONCLUSION: The application of Valdecoxib does not influence anastomotic healing or new vessel formation in the anastomotic region following large bowel resection.

Efficacy of transarterial embolization as definitive treatment in lower gastrointestinal bleeding.

UNLABELLED: Transarterial catheter embolization (TAE) is integral in the management of lower gastrointestinal bleeding (BLGIT). The efficacy of superselective embolization has reduced the need for emergent surgical resection as a treatment modality. OBJECTIVE: To determine the outcomes of TAE in the management of BLGIT in terms of efficacy rates, recurrent bleeding rates and long term results without the need for surgical intervention. METHOD: Patients who underwent TAE for BLGIT between September 2000 and May 2006 were analysed. Data were extracted from the records for analysis. RESULTS: Sixty-eight patients with a mean age of 76 years and equal gender distribution were analysed. Sixty-nine per cent presented with haematochezia, 40% with malena. Sixty-three patients had a prior RBC scan performed, all of which were positive. Colonoscopy was attempted in 18 patients of which four managed to localize the bleeding site. Embolization was performed in these patients using mainly polyvinyl alcohol particles and/or microcoils. The morbidity rate was 21%, comprising mainly fever and nonspecific abdominal pain with only four ischaemic complications and one report of colonic infarction. Early recurrent bleeding occurred in six patients. Three were treated with repeat embolization and two required surgery. There were no mortalities. After a mean follow-up of 12 months, 12 (17.6%) patients developed further episodes of BLGIT, necessitating further intervention. CONCLUSION: Transarterial catheter embolization is effective and safe in the acute management of BLGIT and reduces the need for further definitive surgery in a majority of patients.

Relationship between gut-specific autonomic testing and bowel dysfunction in spinal cord injury patients.

STUDY DESIGN: Investigation of bowel function in 55 patients and 26 healthy volunteers using radiological, anorectal physiological and laser Doppler blood flow monitoring. OBJECTIVES: Bowel dysfunction is common after spinal cord injury (SCI). We aimed to determine whether hindgut testing of autonomic innervation provides insight into presence of symptoms, altered motor function (transit) and level of injury. SETTING: St Mark's Hospital, UK and The Spinal Injuries Unit, Royal National Orthopaedic Hospital, UK. METHODS: A total of 55 patients with chronic complete SCI and 26 healthy volunteers were studied. Twenty-four patients had lesions above T5 and 31 had lesions below T5. Thirty-five patients complained of constipation: 75% (18/24) of patients with lesions above T5 and 55% (17/31) of those with lesions below T5. Gut transit, rectal electrosensitivity and rectal blood flow were measured. RESULTS: Slow gut transit occurred in 65% of patients and in all the 35 patients complaining of constipation. Delay was pancolonic. All patients had an elevated sensory threshold. The threshold was significantly higher in those with subjective constipation (P<0.01), slow transit (P<0.04) and high SCI (P=0.046). Mucosal blood flow was lower in SCI patients with constipation (P<0.04) and slow transit (P<0.03). It was higher than normal in high-SCI volunteers (P=0.056), reflecting loss of sympathetic inhibition. CONCLUSIONS: In SCI, subjective constipation correlates closely with slow gut transit. Delay is pancolonic, regardless of the site of lesion. Sensory testing provides evidence for completeness of lesion, offering further evidence for pain transmission through sympathetic pathways. Studies in SCI patients provide further evidence of mucosal blood flow as a marker of altered autonomic innervation.

[Programmed relaparotomy in treatment of upper mesenteric artery acute occlusion].

Results of surgical treatment and frequency of intestinal necrosis in 44 patients with acute mesenterial circulation failure were analyzed. Instrumental method of detecting the border of necrosis by the infracted intestine should allow refuse programmed relaparotomies in treatment of such patients and perform a sole operation with intestinal resection and anastomosis.

Isolated polyarteritis nodosa of the large bowel: a case report.

Polyarteritis nodosa is a form of vasculitis that affects several organs. Gastrointestinal involvement is frequent, but cases in which the gastrointestinal tract is the only site of disease are rare. In this paper we report a case of a 70-year-old patient with polyarteritis nodosa restricted to the large intestine, who underwent a total colectomy. The patient had no other signs of chronic vasculitis and for this reason surgical treatment resolved the clinical symptoms.