Colonic Vessels Research Articles

Development of human colonic microbiota in the computer-controlled dynamic SIMulator of the GastroIntestinal tract SIMGI

This study presents a computer-controlled dynamic SIMulator of the GastroIntestinal tract, SIMGI, which was designed to simulate the complete processes of digestion and fermentation. The system includes three-stage culture reactors intended to simulate in vitro the microbial conditions of different regions of the human large intestine. The evolution and composition of the microbial community in the ascending (AC), transverse (TC) and descending colon (DC) vessels was evaluated by PCR-DGGE and quantitative PCR. An overall decrease in counts of Bifidobacterium and Prevotella and an increase of Enterobacteriaceae was observed between the inoculation with human faeces and the bacterial community stabilized in the colon vessels. Regarding microbial differentiation, Bacteroides counts were more representative of the AC and TC vessels than the DC compartment. Within the butyrate producer groups, a low occurrence of Clostridium leptum and Ruminoccocus was observed in the AC compartment. The net SCFA production was highest in the AC compartment, whereas the ammonium levels indicated that proteolysis occurred similarly throughout the entire colon compartments. The results observed in the in vitro model SIMGI indicate that it can be used as a tool for studying the effects of diet or food components on modulating the gut microbiota and its metabolic activity.

Dynamic article: surgical anatomical planes for complete mesocolic excision and applied vascular anatomy of the right colon.

Lower local recurrence rates and better overall survival are associated with complete mesocolic excision with central vascular ligation for treatment of colon cancer. To accomplish this, surgeons need to pay special attention to the surgical anatomical planes and vascular anatomy of the colon. However, surgical education in this area has been neglected. The aim of this study is to define the correct surgical anatomical planes for complete mesocolic excision with central vascular ligation and to demonstrate the correct dissection technique for protecting anatomical structures. Macroscopic and microscopic surgical dissections were performed on 12 cadavers in the anatomy laboratory and on autopsy specimens. The dissections were recorded as video clips. Dissections were performed in accordance with the complete mesocolic excision technique on 10 male and 2 female cadavers. Vascular structures, autonomic nerves, and related fascias were shown. Within each step of the surgical procedure, important anatomical structures were displayed on still images captured from videos by animations. Three crucial steps for complete mesocolic excision with central vascular ligation are demonstrated on the cadavers: 1) full mobilization of the superior mesenteric root following the embryological planes between the visceral and the parietal fascias; 2) mobilization of the mesocolon from the duodenum and the pancreas and identification of vascular structures, especially the veins around the pancreas; and 3) central vascular ligation of the colonic vessels at their origin, taking into account the vascular variations within the mesocolonic vessels and the autonomic nerves around the superior mesenteric artery. The limitation of this study was the number of the cadavers used. Successful complete mesocolic excision with central vascular ligation depends on an accurate knowledge of the surgical anatomical planes and the vascular anatomy of the colon.

Anti-VEGF therapy reduces intestinal inflammation in Endoglin heterozygous mice subjected to experimental colitis

Chronic intestinal inflammation is associated with pathological angiogenesis that further amplifies the inflammatory response. Vascular endothelial growth factor (VEGF), is a major angiogenic cytokine that has been implicated in chronic colitis and inflammatory bowel diseases. Endoglin (CD105), a transforming growth factor-β superfamily co-receptor expressed on endothelial and some myeloid cells, is a modulator of angiogenesis involved in wound healing and potentially in resolution of inflammation. We showed previously that Endoglin heterozygous (Eng (+/-)) mice subjected to dextran sodium sulfate developed severe colitis, abnormal colonic vessels and high tissue VEGF. We therefore tested in the current study if treatment with a monoclonal antibody to VEGF could ameliorate chronic colitis in Eng (+/-) mice. Tissue inflammation and microvessel density (MVD) were quantified on histological slides. Colonic wall thickness, microvascular hemodynamics and targeted MAdCAM-1(+) inflamed vessels were assessed in vivo by ultrasound. Mediators of angiogenesis and inflammation were measured by Milliplex and ELISA assays. Colitic Eng (+/-) mice showed an increase in intestinal inflammation, MVD, colonic wall thickness, microvascular hemodynamics and the number of MAdCAM-1(+) microvessels relative to colitic Eng (+/+) mice; these parameters were all attenuated by anti-VEGF treatment. Of all factors up-regulated in the inflamed gut, granulocyte colony-stimulating factor (G-CSF) and amphiregulin were further increased in colitic Eng (+/-) versus Eng (+/+) mice. Anti-VEGF therapy decreased tissue VEGF and inflammation-induced endoglin, IL-1β and G-CSF in colitic Eng (+/-) mice. Our results suggest that endoglin modulates intestinal angiogenic and inflammatory responses in colitis. Furthermore, contrast-enhanced ultrasound provides an excellent non-invasive imaging modality to monitor gut angiogenesis, inflammation and responses to anti-angiogenic treatment.

A middle mesenteric artery

In 114 cases of the transverse colon isolated from cadavers (50 male, 64 female), anatomical examinations of the arterial system of the colon were performed. Arteriograms were obtained after dissecting and contrasting the colonic vessels with Mixobar contrast. In one case, on arteriography of the colon with its mesentery isolated from a 55-year-old male cadaver, a rare anatomical variant was found. The third mesenteric artery originated directly from the aorta—halfway between the superior and inferior mesenteric arteries and ascended obliquely in the direction of the hepatic flexure of the colon. Supply area of the artery was typical for the middle colic branch of the superior mesenteric artery: the distal segment of the ascending colon and the transverse colon. Such a variation, although very rare, may have particular impact on diagnosis and even the method and range of surgery.

Laparoscopic extended right hemicolectomy with D3 lymphadenectomy using a medial-to-lateral approach

Lapareseopic colectomy is commonly performed,but laparoscopic extended right hemicolectomy with D3 lymphadenectomy for cancer located at hepatic flexure of the colon is a complex procedure,even in the hands of experts.Laparoscopic dissection of the lymph nodes around the middle colonic and right gastroepiploic vessels are so complicated that precise vascular anatomy and surgical plane are essential to complete this procedure safely.We herein describe a standard technique for performing laparoscopic extended right hemicolectomy with D3 lymphadenectomy using a medial-to-lateral approach.The main surgical plane of this procedure is the right Toldt's space.The superior mesenteric vein (SMV) is the most important anatomical landmark of vascular dissection.Medial-to-lateral approach makes it easy to locate the right Toldt's space and the SMV. Key words: Colonic neoplasms ; Laparoscopy ; Extended right hemicolectomy ; Anatomical landmark ; Complete mesocolic excision ;

Colon interposition for oesophageal replacement

The choice of the colon as an oesophageal substitute results primarily from the unavailability of the stomach. However, given its durability and function, colon interposition keeps elective indications in patients with benign or malignant oesophageal disease who are potential candidates for long survival. The choice of the colonic portion used for oesophageal reconstruction depends on the required length of the graft, and the encountered colonic vascular anatomy, the last being characterised by the near-invariability of the left colonic vessels, in contrast to the vascular pattern of the right side of the colon. Accordingly, the transverse colon with all or part of the ascending colon is the substitute of choice, positioned in the isoperistaltic direction, and supplied either from the left colic vessels for long grafts or middle colic vessels for shorter grafts. Technical key points are: full mobilisation of the entire colon, identification of the main colonic vessels and collaterals, and a prolonged clamping test to ensure the permeability of the chosen nourishing pedicle. Transposition through the posterior mediastinum in the oesophageal bed is the shortest one and thereby offers the best functional results. When the oesophageal bed is not available, the retrosternal route is the preferred alternative option. The food bolus travelling mainly by gravity makes straightness of the conduit of paramount importance. The proximal anastomosis is a single-layer hand-fashioned end-to-end anastomosis to prevent narrowing. When the stomach is available, the distal anastomosis is best performed at the posterior part of the antrum for the reasons of pedicle positioning and reflux prevention, and a gastric drainage procedure is added when the oesophagus and vagus nerves have been removed. In the other cases, a Roux-en-Y jejunal loop is preferable to prevent bile reflux into the colon. Additional procedures include re-establishment of the colonic continuity, a careful closure of the mesentery to avoid a further internal hernia, and routine appendectomy. When applying these technical aids, the chances of achieving a viable and well-functioning colon graft are excellent.

Arabinoxylan‐oligosaccharides (AXOS) affect the protein/carbohydrate fermentation balance and microbial population dynamics of the Simulator of Human Intestinal Microbial Ecosystem

SummaryArabinoxylan‐oligosaccharides (AXOS) are a recently newly discovered class of candidate prebiotics as – depending on their structure – they are fermented in different regions of gastrointestinal tract. This can have an impact on the protein/carbohydrate fermentation balance in the large intestine and, thus, affect the generation of potentially toxic metabolites in the colon originating from proteolytic activity. In this study, we screened different AXOS preparations for their impact on the in vitro intestinal fermentation activity and microbial community structure. Short‐term fermentation experiments with AXOS with an average degree of polymerization (avDP) of 29 allowed part of the oligosaccharides to reach the distal colon, and decreased the concentration of proteolytic markers, whereas AXOS with lower avDP were primarily fermented in the proximal colon. Additionally, prolonged supplementation of AXOS with avDP 29 to the Simulator of Human Intestinal Microbial Ecosystem (SHIME) reactor decreased levels of the toxic proteolytic markers phenol and p‐cresol in the two distal colon compartments and increased concentrations of beneficial short‐chain fatty acids (SCFA) in all colon vessels (25–48%). Denaturant gradient gel electrophoresis (DGGE) analysis indicated that AXOS supplementation only slightly modified the total microbial community, implying that the observed effects on fermentation markers are mainly caused by changes in fermentation activity. Finally, specific quantitative PCR (qPCR) analysis showed that AXOS supplementation significantly increased the amount of health‐promoting lactobacilli as well as of Bacteroides–Prevotella and Clostridium coccoides–Eubacterium rectale groups. These data allow concluding that AXOS are promising candidates to modulate the microbial metabolism in the distal colon.

Hyaluronan (HA) deposition precedes and promotes leukocyte recruitment in intestinal inflammation.

Increased hyaluronan (HA) deposition is a common feature of inflamed tissues, including inflammatory bowel disease (IBD)-involved intestines. However, whether HA accumulation promotes or is the result of intestinal inflammation is unknown. Using the mouse dextran sulfate sodium (DSS)-induced experimental model of colitis, we investigated changes in HA deposition in the colon over time in conjunction with evolving pathological changes of tissue architecture. Profound changes in colon HA deposition occurred within 3-7 days of oral DSS administration and, more important, they preceded the inflammatory infiltrate. Interestingly, HA deposition within blood vessels of the colon is observed as early as 3 days during the course of colitis induction, well before any significant inflammatory infiltrate. HA deposition is also observed in blood vessels of inflamed human colon of IBD patients. We determined that human intestinal endothelial cells generate HA in response to proinflammatory stimuli by demonstrating a TNF-alpha-induced increase in hyaluronan synthase-3 mRNA expression and the accumulation of HA cable-like structures that are adhesive for leukocytes. Additionally, IBD mucosal endothelial cells produce higher levels of cell surface HA in response to TNF-alpha than non-IBD control cells. Therefore, HA deposition is an early event in inflamed gut tissue, preceding and likely promoting leukocyte infiltration.

Bridging Mucosal Vessels Associated with Rhythmically Oscillating Blood Flow in Murine Colitis

Oscillatory blood flow in the microcirculation is generally considered to be the result of cardiopulmonary influences or active vasomotion. In this report, we describe rhythmically oscillating blood flow in the bridging vessels of the mouse colon that appeared to be independent of known biological control mechanisms. Corrosion casting and scanning electron microscopy of the mouse colon demonstrated highly branched bridging vessels that connected the submucosal vessels with the mucosal plexus. Because of similar morphometric characteristics (19 +/- 11 microm vs. 28 +/- 16 microm), bridging arterioles and venules were distinguished by tracking fluorescent nanoparticles through the microcirculation using intravital fluorescence videomicroscopy. In control mice, the blood flow through the bridging vessels was typically continuous and unidirectional. In contrast, two models of chemically induced inflammation (trinitrobenzenesulfonic acid and dextran sodium sulfate) were associated with a twofold reduction in flow velocity and the prominence of rhythmically oscillating blood flow. The blood oscillation was characterized by tracking the bidirectional displacement of fluorescent nanoparticles. Space-time plots and particle tracking of the oscillating segments demonstrated an oscillation frequency between 0.2 and 5.1 cycles per second. Discrete Fourier transforms demonstrated a power spectrum composed of several base frequencies. These observations suggest that inflammation-inducible changes in blood flow patterns in the murine colon resulted in both reduced blood flow velocity and rhythmic oscillations within the bridging vessels of the mouse colon.

Genetic Evidence for a Protective Role for Heat Shock Factor 1 and Heat Shock Protein 70 against Colitis

Inflammatory bowel disease (IBD) involves infiltration of leukocytes into intestinal tissue, resulting in intestinal damage induced by reactive oxygen species (ROS). Pro-inflammatory cytokines and cell adhesion molecules (CAMs) play important roles in this infiltration of leukocytes. The roles of heat shock factor 1 (HSF1) and heat shock proteins (HSPs) in the development of IBD are unclear. In this study, we examined the roles of HSF1 and HSPs in an animal model of IBD, dextran sulfate sodium (DSS)-induced colitis. The colitis worsened or was ameliorated in HSF1-null mice or transgenic mice expressing HSP70 (or HSF1), respectively. Administration of DSS up-regulated the expression of HSP70 in colonic tissues in an HSF1-dependent manner. Expression of pro-inflammatory cytokines and CAMs and the level of cell death observed in colonic tissues were increased or decreased in DSS-treated HSF1-null mice or transgenic mice expressing HSP70, respectively, relative to control wild-type mice. Relative to macrophages from control wild-type mice, macrophages prepared from HSF1-null mice or transgenic mice expressing HSP70 displayed enhanced or reduced activity, respectively, for the generation of pro-inflammatory cytokines in response to lipopolysaccharide stimulation. Suppression of HSF1 or HSP70 expression in vitro stimulated lipopolysaccharide-induced up-regulation of CAMs or ROS-induced cell death, respectively. This study provides the first genetic evidence that HSF1 and HSP70 play a role in protecting against DSS-induced colitis. Furthermore, this protective role seems to involve various mechanisms, such as suppression of expression of pro-inflammatory cytokines and CAMs and ROS-induced cell death.

Small Bowel and Colon Transplantation in Rats Using Porto-Portal Cuff Anastomosis

Portal versus systemic venous drainage and colon grafting are major controversies in the techniques of intestinal transplantation. The rat is the best animal for research in this field. Nevertheless, this model requires complex microvascular anastomoses that are responsible for the high incidence of technical failures. A cuff technique is an easier anastomosis method than a hand-suture. We describe a simplified rat model of small bowel and colon transplantation using a porto-portal cuff anastomosis. Donor The entire small bowel, cecum, and ascending colon are harvested on a vascular pedicle, consisting of a long aortomesenteric conduit and portal vein. The right colonic vessels are preserved. The graft is flushed and a cuff device is placed on the end of the portal vein. Recipient The graft is implanted through an end-to-side aorto-aorta hand-sewn anastomosis. A segment between the first and second jejunal branch is isolated between clamps to insert into the portal cuff. After reperfusion, the recipient’s mesentery is divided just below the cuff anastomosis. The recipient jejunum, ileum, and ascending colon are removed en bloc, and the graft is anastomosed in continuity with the remaining naive intestine concluding the operation. This simplified technique surmounts the technical obstacles in rats because it is easily and quickly performed, maintaining the physiological portal drainage, preserving graft ileocecal valve and ascending colon, and reaching acceptable success after a short period of training.

Simplified Rat Model of Intestinal Transplantation

Rat intestinal transplantation is an optimal model for research; nevertheless, it requires a complex and difficult microsurgical technique (1–5). We have recently developed a simplified rat model for intestinal transplantation using portal cuff anastomosis to overcome these technical difficulties (Fig. 1A).FIGURE 1.: (A) Figure illustrating the present model of intestinal transplantation. G, intestinal graft in shady color; SMA, superior mesenteric artery of the graft; VC, recipient vena cava; AO, recipient aorta. (B) Micropicture (16×) showing details of the portal cuff.Preoperative procedures, anesthesia and laparotomy are performed as previously described (1–4). In the donor operation, middle and descending colons are isolated from small bowel and ascending colon. Superior mesenteric vein is dissected and encircled. Splenic and pyloric veins are divided and portal vein is dissected up to hepatic hilum. Abdominal aorta is dissected and celiac trunk, right renal artery and lumbar branches are divided. Aorta is clamped at the diaphragm, tied below the mesenteric artery and this arterial segment is resected allowing a long aortomesenteric conduit. Entire small bowel, cecum and ascending colon are harvested on a vascular pedicle consisting of right colonic vessels, aortomesenteric conduit and portal vein. The graft is flushed and stored in cold preservation solution. Polyethylene catheter is used to create the cuff as described elsewhere (5). In this modified technique, the vein is introduced into the cuff and everted, covering the outer wall and fixed with three equidistant stitches (Fig. 1B). In the recipient, the superior mesenteric vein is exposed, and a segment between the first and second jejunal branch is dissected and prepared for cuff anastomosis. Eventually, the second jejunal branches and the right colonic vein may be divided in order to increase this segment. The graft is implanted in the recipient with an end-to-side aorto-aorta anastomosis as previously described (1–5). The dissected segment of mesenteric vein is isolated between clamps to insert the portal cuff and a 6-0 suture is used to fix the cuff into recipient’s mesenteric vein. The clamps are released and immediate graft reperfusion is observed. The recipient jejunum, ileum, cecum, and ascending colon are removed en bloc. Finally, anastomosis between the graft and the remaining intestine restores the digestive tract (Fig. 1A). The present model offers many possibilities for intestinal transplantation research with the following advantages: reconstitutes the natural and physiologic portal graft drainage; the portal cuff anastomosis is performed within few minutes without bleeding or venous thrombosis. This alternative technique avoids recipient visceral ischemia and hemodynamic instability because there is no obstruction on inferior vena cava and portal vein. Furthermore, it maintains grafts ileocecal valve and preserves the extrinsic enervation along the mesenteric-aortic segment that may improve bowel movement. This modified technique can be easily performed within two hours after a short period of training (8±3 week) and may reach excellent success rates. This rat model may surmount technical obstacles precluding microsurgical techniques and may ultimately spread this model in centers with low technical resources. Flávio H.F. Galvão Rafael M.N. Santos Marcel A.C. Machado Telesforo Bacchella Marcel C.C. Machado Transplantation and Liver Surgery Discipline University of Sao Paulo School of Medicine Sao Paulo, Brazil

Intravascular T-cell lymphoma with bowel involvement: Case report and literature review

Intravascular lymphoma (IVL) is a rare form of non-Hodgkin lymphoma characterized by massive proliferation of large, neoplastic cells in small- and medium-sized blood vessels. Most cases of IVL are of B-cell immunophenotype; fewer than 15 cases of T-cell IVL have been reported. A 23-year-old male presented with acute abdominal pain, fever, and tender lower abdomen. Pathology at laparotomy revealed infiltration of colonic vessels with large lymphoid cells compatible with IVL. We reviewed all cases of IVL diagnosed at the Queen Elizabeth II Health Sciences Centre in Halifax, Nova Scotia, from August 1992 to August 2002. A literature review was also performed. Five additional cases of IVL were identified at this institution during a 10-year period. Three patients presented with neurological symptoms, and two with abdominal pain. In 4 of 5 cases, patients died of lymphoma within 3 months of presentation; one patient experienced a 10-month remission. While visceral involvement with IVL is common at autopsy, IVL presenting as an acute abdomen in an immunocompetent patient has not previously been described. Among the 15 cases of T-cell IVL reported in the literature, only two occurred in people under age 30. Given the rarity of T-cell IVL, it is remarkable that three cases of T-cell IVL have been diagnosed at our institution during a 10-year period.

Localization of Protein Z (PZ) In Situ in Human Neoplastic Tissues.

Tumor cells synthesize and release procoagulants that lead to multi-factorial activation of factor X and subsequent thrombin generation and fibrin formation that in turn contribute to tumor growth and metastatic spread. The activity of factor Xa is inhibited by TFPI (tissue factor pathway inhibitor). Another mechanism of direct inhibition of factor Xa involves protein Z (PZ). Protein Z is a 62-kD, vitamin K-dependent plasma nonpeptidase glycoprotein, which, in complex with PZ-dependent protease inhibitor (ZPI), inhibits factor Xa in the presence of Ca2+ and phospholipids. However, data on the presence of the PZ in tumor malignant tissue are lacking. Results obtained from randomized clinical trials indicate that inhibition of blood coagulation may improve the results of anticancer therapy in selected tumor types. The purpose of the study was to evaluate the localization of PZ in situ in colon, breast, gastric, laryngeal, pancreatic, renal, endometrial cancer, non-small cell lung cancer (NSCLC), malignant melanoma and glial neoplasms. Studies were performed on tumor fragments obtained at surgical treatment of proviously untreated patients. Immunohistochemical procedures using the ABC method employed a specific polyclonal antibody directed against human PZ antigen. Protein Z was localized in cancer cell bodies in all types of malignant tumors examined. Staining intensity was more pronounced in less differentiated cancer cells of anaplastic gliomas. In contrast, more differentiated cancer cells of gastric cancer revealed stronger staining than more malignant ones. Cancer cell bodies of NSCLC and renal cancer were characterized by weak intensity of staining for PZ. In the case of pancreatic and renal cancer, as well as malignant melanoma, the intensity of staining for PZ in cancer cell bodies was irregular: both high and low expression of PZ was observed independent of the degree of malignancy. The expression of PZ was also revealed in association with tumor infiltrating macrophages in colon cancer, NSCLC and malignant melanoma. Furthermore, PZ was localized in small blood vessels of colon, renal, endometrial, gastric cancer, NSCLC, malignant melanoma and glial neoplasms. The observed localization of PZ, particularly in association with cancer cells of all malignant tumors examined, suggests that this protein may exert regulatory effects on tumor growth and metastatic dissemination.

Transplanted bone marrow cells preferentially home to the vessels of in situ generated murine tumors rather than of normal organs.

Transplanted bone marrow-derived (BM) cells have been shown to home into the tumor vessels of s.c. implanted tumor models and to functionally contribute to tumor neoangiogenesis and tumor growth. However, whether BM cells contribute to the vessels of in situ developing tumors remains unknown. We have taken advantage of the in situ generation of mammary tumors in transgenic mice carrying the polyoma virus middle T oncogene (MMTV-PyVT) to determine whether transplanted BM cells home to and incorporate into the intratumoral vessels. Unfractionated BM from lacZ+ROSA 26 mice was used to rescue irradiated MMTV-PyVT transgenic mice or their wild-type congenics. All transgenic mice were sacrificed when they developed easily palpable mammary tumors. BM cells recruited and incorporated into the vasculature were identified by coexpression of lacZ and CD31, evidence that these cells had a distinctive, elongated appearance and that they lined the vessel structures. We found that BM cells home to and incorporate into 1.3% of the vessels of all in situ generated mammary adenocarcinomas examined (n=8). In contrast, BM cells did not recruit into the vessels of colon or liver of the tumor-bearing mice. Whether these cells contribute to new vessel formation via vasculogenesis or angiogenesis or simply attach to, and integrate into, the growing tips or shafts of pre-existing vessels has to be determined. BM could be used as a vehicle for the specific transport of antiangiogenic signals into the tumor vascular bed.

Long-term functional results of transhiatal oesophagectomy and colonic interposition for caustic oesophageal stricture

Various surgical procedures have been advocated for the replacement of the scarred esophagus in children. The authors report on their experience with esophago-coloplasty. Over a 10-year period, 100 children (62 boys, 38 girls) with intractable caustic stricture of the esophagus underwent transhiatal esophagectomy and left colonic interposition. Their age at time of surgery ranged from 14 months to 8 years (mean, 3.4 years). The patients were followed up for a period from 5 to 15 years postoperatively. There were 3 deaths from respiratory failure. Stricture of the cervical esophagocolic anastomosis occurred in 6 patients and needed repeated dilatations (2 patients) and surgical revision (4 patients). Mild redundancy of the colonic substitute in the chest was noted in 5 cases, but there was no dysphagia necessitating revision of the colonic transplant. Peptic ulcer or symptomatic gastrocolic reflux was not seen. All patients are able to swallow and eat a normal diet. They gain weight and enjoy a normal life pattern. It is concluded that isoperistaltic left colon, based on both the ascending and descending branches of the left colonic vessels with simultaneous esophagectomy utilizing the transhiatal approach, is the best substitute for a scarred esophagus in children with satisfactory long-term results.—Thomas A. Angerpointner

Temporal changes in colonic vascular architecture and inflammatory mediator levels in animal models of colitis.

This study investigated the temporal relationship between inflammatory mediator production and colonic vascular architecture in rabbit and rat trinitrobenzene sulfonic acid (TNBS) models of colitis. In both species significant colonic damage and loss of mucosal integrity occurred over time. In the rabbit there was a significant increase in TxB2 levels in the muscularis propria and mucosa at 1, 6, and 48 hr after TNBS, with a significant elevation in PGE2 production in the muscularis propria at 48 hr. However, elevated mediator levels were not associated with measurable changes in vascular architecture. In contrast, significant changes in the numbers and diameters of colonic blood vessels were observed in the rat, in the absence of significant elevations in TxB2 or PGE2 levels. These data suggest that the role of lipid mediators in acute colitis is species-dependent and, although there are corresponding gross and microscopic changes in both models, these occur through disparate mechanisms.

Laparoscopically assisted subtotal colectomy for slow-transit constipation.

When medical therapy fails, slow-transit constipation (STC), a condition seen almost exclusively in women, can be treated surgically. The aim of this study was to describe our results with laparoscopically assisted subtotal colectomy (LASC) for STC. Over a 22-month period, four female patients underwent LASC with ileorectal anastomosis for STC at our hospital. The preoperative workup included clinical assessment, evacuation proctography, rectoanal manometry, and colonic transit measurement. Mobilization of the whole colon and ligation and division of colonic mesenteric vessels with preservation of the omentum were achieved laparoscopically. Through a small Pfannenstiel incision, the colon was removed from the abdomen, leaving a 15-cm rectal stump in situ. The rectal stump was fully mobilized posteriorly, a side-to-end ileorectal anastomosis was fashioned, and the rectal stump was fixed onto the presacral fascia with sutures. The operating time ranged from 150 to 260 min and blood loss was minimal. There were no conversions to open surgery. The postoperative course was uneventful in all patients but one, a 47-year old woman who had transient severe abdominal distension, pain, and frequent small-volume bowel movements. All patients were discharged by the 4th to 10th postoperative day. At 9-month follow-up, all of our patients had normal anorectal function with two to four solid bowel movements per day. Although it is a technically demanding procedure, laparoscopically assisted colectomy for slow-transit constipation, can be achieved safely.

En bloc resection for locally advanced cancer of the pancereas: Is it worthwhile?

The benefit of radical surgical resection of contiguously involved structures for locally advanced pancreatic cancer is unclear. The aim of this study was to examine patient outcome after extended pancreatic resection for locally advanced tumors and to determine if any subset of extended resection affected outcome. We retrospectively reviewed the records of 116 patients with adenocarcinoma of the pancreas, who underwent extirpative pancreatic surgery between 1987 and 2000. Of the 116 patients, 37 (32%) required resection of surrounding structures (group I), and 79 patients (68%) underwent standard pancreatic resections (group II). In all cases, all macroscopic disease was excised. In group I a total of 46 contiguously involved structures were resected: vascular in 25 patients (54%), mesocolon in 16 (35%) (colic vessels in 3, colon in 13), adrenal in three (7%), liver in one (2%), stomach in one (2%) (for a tumor in the tail of the pancreas), and multiple structures in four. Excision of regional blood vessels included the superior mesenteric vein and/or portal vein in 16, hepatic artery in five, and celiac axis in four. No differences between groups I and II were detected for any of the following parameters: age, sex, history of previous operation, estimated blood loss, or hospital stay. For the entire cohort the morbidity and mortality were 38% and 1.7%, respectively, and these rates were similar in the two groups. Adjuvant therapy was administered to more than 90% of patients in both groups. However, patients in group I were more likely to have received neoadjuvant therapy (76% vs. 42%, P = 0.001). Total pancreatectomy and distal pancreatectomy were more often performed in group I (P = 0.005). Additionally, the median operative time was longer (8.5 hours compared to 6.9 hours (P = 0.0004)). Both groups had similar rates of microscopically positive margins and involved lymph nodes, as well as total number of lymph nodes removed. The median survival was 26 months for patients in group I and 16 months for patients in group II (P = 0.08). The median disease-free survival for groups I and II was 16 months and 14 months, respectively (P = 0.88). In comparing patients in group I, who underwent vascular resection vs. mesocolon (colon or middle colic vessels) resection, the median survival was 26 months and 19 months, respectively (P = 0.12). We were unable to detect a difference in outcome for patients with locally advanced cancers requiring extended pancreatic resections compared to patients with standard resections. En bloc resection of involved surrounding structures, to completely extirpate all macroscopic disease, may be of benefit in selected patients with locally advanced disease, particularly when combined with preoperative chemoradiation therapy.

In vitro pharmacologic effect of two endothelin-1 antagonists on equine colonic arteries and veins.

To evaluate the effectiveness of 2 potential endothelin (ET)-1 antagonists in blocking the contractile responses of equine colonic vessels to increasing concentrations of ET-1. Mesenteric vessels from 6 clinically healthy horses. Colonic vessels (arterial and venous rings) were placed in organ baths with oxygenated Tyrode solution at 37 C. Each was attached to a force transducer interfaced with a polygraph, and 2 g of tension was applied and equilibrated for 45 minutes. Then, B-1 (PD 142893) and B-2 (PD 145065) ET-1 antagonists were tested. One ring from each vessel type was used as a control for determining concentration-response relationships of ET-1 (10(-10) to 10(-6)M). Three rings of each vessel type were incubated with 3 concentrations of each antagonist (10(-7), 10(-6), and 10(-5) M) for 30 minutes before ET induced contractions were determined. The maximum contractile response and pA2 values were determined. Vessels contracted in a concentration-dependent manner to ET-1. Arteries responded slowly but reached greater contractions. Veins responded immediately with sustained contractions. Both antagonists inhibited contractions in a concentration-dependent manner with significant differences at 10(-6) and 10(-5)M for arteries and 10(-5) M for veins. Complete blockade of contractions was observed with B-2 (10(-5)M). The pA2 values for B-1 were 8.26 and 6.82 for arteries and veins, respectively, whereas they were 8.25 and 7.21 for B-2. Both antagonists effectively blocked ET-1-induced contractions of equine colonic vessels. Because B-2 is water soluble and caused complete blockade at 10(-5) M, it appears to be the preferred antagonist.