Colonic Wall Thickening Research Articles

Graft-Versus-Host Disease: Not Only in Allogeneic Hematopoietic Cell Transplant

Acute Graft versus Host Disease is a severe and common complication seen in allogeneic hematopoietic cell transplant (HCT) recipients and whose clinical manifestations include maculopapular rash, abdominal cramps with diarrhea and rising bilirubin levels. We present the case of a 38 year old male who underwent autologous HCT for a diagnosis of T cell lymphoma and was consulted to gastroenterology due to diarrhea. Upon our evaluation patient reported 12 episodes of watery voluminous diarrhea with occasional blood, that started 14 days after transplant. There was associated crampy lower quadrant abdominal pain, nausea, anorexia with weight loss. Physical examination revealed a cachectic man that was tachycardic and with hyperactive bowel sounds. Hematology revealed a normocytic anemia of 9.0 g/dL with normal WBC and platelets. Chemistry remarkable for hypokalemia (2.6 mEq/L), hypomagnesemia (1.4 mEq/L), hypoalbuminemia (1.2 g/dL), with preserved renal function. Liver tests revealed cholestasis (ALP: 313) and normal liver enzymes. Stool infectious workup was unremarkable. Abdominopelvic CT scan with IV contrast showed diffuse small bowel and colon wall thickening. Sigmoidoscopy was performed for mucosal visualization. The scope was advanced to mid transverse colon where a diffuse, whitish, erythematous and granular nodularity with loss of vascular pattern was found. There was no ulceration, friability or spontaneous bleeding. Random biopsies taken that where negative for CMV, HSV, EBV but showed chronic colitis with crypt loss and regenerative changes. Changes consistent with acute graft vs. host disease (Grade III). Systemic and topical steroids at high doses started with initial improvement of diarrhea at the writing of this abstract. This is a unique case in that graft vs. host is relatively common after allogeneic HCT transplant but not autologous. Although not the first case, previously reported cases of autologous graft vs. host tend to be milder and have more skin involvement. This solidifies the importance of having a broad differential diagnosis in post transplant patients, so that prompt recognition of this unusual diagnosis can be done and improve outcomes.

Metastatic Gastric Cancer Presenting as Periorbital Edema

A 53 year old male presented with recent labs and imaging concerning for periorbital cellulitis. The patient was initially admitted by ophthalmology and managed with antibiotics. He displayed minimal improvement with antibiotics, leading to the addition of systemic steroids. His condition deteriorated the following day when he developed hematemesis. Antibiotics were therefore escalated with the addition of IV Pantoprazole, and steroids were discontinued. EGD showed a large, non-bleeding ulcer with a visible vessel in the gastric body. Small, clean-based ulcers were also seen in the body and antrum. Diffuse, friable mucosa was noted throughout the stomach and biopsies were taken due to concern for malignancy. Right orbital biopsy and CT chest/abdomen/pelvis was also ordered to further evaluate for malignancy. CT showed bilateral pulmonary emboli, retroperitoneal soft tissue infiltrates, and bladder and colonic wall thickening. The patient's hematemesis recurred, necessitating repeat EGD with epinephrine injections and bipolar cautery in order to achieve hemostasis. Gastric biopsies revealed invasive and poorly differentiated Signet Ring Cell Carcinoma (SRCC) with a background of severe ulcerated gastritis and H. pylori. Antibiotics were de-escalated and tailored to treat H. Pylori. Colonoscopy was performed given CT findings of circumferential stenosis within the ascending and transverse colon. Colonic and right orbit biopsies were consistent with metastatic SRCC. The patient was discharged home after the initial work up with future plans for orbital radiation, chemotherapy initiation, and repeat EGD. The number of cases of gastric SRCC has steadily increased over the last few decades, despite an overall decline in incidence in gastric cancer worldwide. SRCC is a distinct diffuse-type gastric adenocarcinoma based on its histological and clinical features. Patients typically present in advanced stages and carry a poor prognosis. Synchronous SRCC is rare, although the colon appears to be the most common synchronous cancer associated with gastric SRCC. Gastric SRCC has a predilection for metastasis to the peritoneum, lung, bladder, and in rare cases the optic nerve. H. Pylori may be associated with SRCC; treatment of H. Pylori improves mucosal healing and may aid in interventional therapies. This case represents a unique presentation of an advanced stage synchronous gastric and colonic SRCC.2661_A Figure 1. Periorbital edema of the right eye.2661_B Figure 2. Malignant ulcer with visible vessel and active bleeding. Friable mucosa surrounding ulcer.2661_C Figure 3. Orbital biopsy showing metastatic signet ring cell carcinoma (H&E, 400x).

Novel peptide inhibitor of dipeptidyl peptidase IV (Tyr-Pro-D-Ala-NH2) with anti-inflammatory activity in the mouse models of colitis

Protease inhibition has become a new possible approach in the inflammatory bowel disease (IBD) therapy. A serine exopeptidase, dipeptidyl peptidase IV (DPP IV) is responsible for inactivation of incretin hormone, glucagon-like peptide 2 (GLP-2), a potent stimulator of intestinal epithelium regeneration and growth. Recently we showed that the novel peptide analog of endomorphin-2, EMDB-1 (Tyr-Pro-D-ClPhe-Phe-NH2) is a potent blocker of DPP IV and exhibits an anti-inflammatory activity in vivo. The aim of this study was to design, synthesize and characterize the therapeutic activity and mechanism of action of a series of novel EMDB-1 analogs. The inhibitory potential of all peptides was evaluated using the fluorometric screening assay employing Gly-Pro-Aminomethylcoumarin (AMC) to measure DPP IV activity. Consequently, one compound, namely DI-1 was selected and its therapeutic activity evaluated using mouse models of experimental colitis (induced by TNBS and DSS). Macro- and microscopic score, ulcer score, colonic wall thickness as well as myeloperoxidase activity were measured. We showed that DI-1 blocks DPP IV in vitro (IC50 = 0.76 ± 0.04 nM) and attenuates acute, semichronic and relapsing TNBS- as well as DSS-induced colitis in mice after topical administration. Its anti-inflammatory action is associated with the increase of colonic GLP-2 but not GLP2 receptor or DPP IV expression. Our results validate DPP IV as a pharmacological target for the anti-IBD drugs and its inhibitors, such as DI-1, have the potential to become valuable anti-inflammatory therapeutics.

Abstract 673: Preoperative radiation therapy in advanced carcinoma colon with post-colostomy intestinal obstruction: The first report

Abstract Introduction We report the use of preoperative radiotherapy in a moribund patient with advanced carcinoma colon with complete intestinal obstruction who had undergone colostomy for a previous episode of intestinal obstruction. Methods Fifty-five-year-old man presented in Dec 2016 with acute intestinal obstruction with pain in abdomen and vomiting for 3 months. On exploratory laparotomy, a 12x15 cm hard mass in splenic flexure of colon was found involving root of mesentery, superior mesenteric vein and third part of duodenum and abutting tail of pancreas. Finding it unresectable, loop transverse colostomy was performed. He was started on Capecitabine. In Mar 2017, he presented to us in emaciated condition weighing 28 kilograms with acute intestinal obstruction with a large abdominal mass. He was started on nasogastric aspiration with total parenteral nutrition. Imaging revealed a 14x19 cm large abdominal mass involving pancreas, duodenum, spleen and transverse colon with dilated stomach. In view of poor general condition and advanced disease, the prognosis was discussed with the family and the idea of radiotherapy to relieve intestinal obstruction was discussed with family. After taking the consent, he was started on radiation therapy with 1.8 Gy per fraction after three-dimensional conformal radiation planning to spare maximum bowel. After 11 fractions, the patient started passing stools through the stoma. He was gradually started on enteral nutrition and was discharged to continue radiation therapy on outpatient basis. After 15 fractions, planning PET-CT scan was taken for adaptive therapy to make changes as per the reducing tumor size. He was also started on capecitabine as he was taking orally well. He completed 45 Gy in 25 fractions over 5 weeks. One month after completion of radiation therapy, he was found to be doing well and was planned for definitive surgery. Six weeks after the radiation therapy completion, extended left hemicolectomy with distal pancreatico-splenectomy and colostomy closure was performed. Histopathology showed residual viable poorly differentiated adenocarcinoma invading full thickness of colonic wall into pericolic soft tissues with a discontinuous microscopic nodular tumor deposit in pericolic soft tissue with all margins and nodes negative. Postoperatively, he developed biliary leak which healed with conservative management. Six weeks after the surgery, he recovered completely and was started on adjuvant Capecitabine. Five months after the surgery, he is doing well and is on oral Capecitabine. Conclusion To our knowledge, this is the first reported case of preoperative radiation therapy in advanced carcinoma colon and also in the setting of intestinal obstruction. Radiotherapy should be further tested in setting of malignant intestinal obstruction due to unresectable carcinoma colon and may spare patients with ileo/colostomy. Citation Format: Amit Jain, Elumalai L, Punam Goswami. Preoperative radiation therapy in advanced carcinoma colon with post-colostomy intestinal obstruction: The first report [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 673.

Poor Agreement Between Imaging and Histologic and Colonoscopy Findings in Pediatric Patients.

Computed tomography scans (CTs), more recently magnetic resonance imaging, are often used to assess the gastrointestinal tract in patients complaining of abdominal pain. We aim to determine the strength of agreement among abdominal imaging, endoscopic, and histologic findings. Retrospective chart review of pediatric patients who underwent colonoscopy between January 1, 2012, and December 31, 2014, at Women and Children's Hospital of Buffalo. Patients who had abdominal and pelvic CTs or magnetic resonance imaging within 30 days before or after a colonoscopy were included. One hundred two patients were included: mean age 12.7 ± 3.8 years, 66% girls. A total of 109 imaging studies were performed. Overall 61% of imaging studies were abnormal. The most frequent intestinal radiological findings were colonic wall thickening (CWT) (55%) and colonic wall enhancement (CWH) (24%). Free fluid (20%) and fat stranding (18%) were the most common extra-intestinal findings. Imaging studies agreed with histology in 81% and with colonoscopy in 75% with a moderate strength of agreement (k: 0.59 and 0.466, respectively). CWT agreed with histology in 74% with a moderate strength of agreement (k: 0.47). History of weight loss (OR 5.35, P = 0.041), chronic diarrhea (OR 4.22, P = 0.014), a positive lactoferrin (OR 7.00, P = 0.011), and presence of CWT on imaging study (OR 5.20, P = 0.001) were predictive of having abnormal histology. The strength of agreement among imaging, endoscopic, and histologic findings was suboptimal. Colonoscopy and imaging are both likely to be necessary in patients with suspected inflammatory bowel disease. Although colonoscopy may be superior in diagnosis of colitis, imaging may provide more information regarding small bowel disease.

Portal congestion and intestinal edema in hospitalized patients with heart failure.

An interaction between the intestine and cardiovascular disease has been suggested. We thought to clarify the association between intestinal conditions and clinical outcomes in patients with heart failure (HF). Hemodynamic parameters in intestinal vessels [superior mesenteric artery (SMA), inferior mesenteric artery (IMA), and portal vein (PV)] and average colon wall thickness (aCWT) from the ascending colon to sigmoid colon were evaluated in 224 hospitalized HF patients. Echocardiographic parameters and composite event rates (all-cause mortality, readmission for HF deterioration, major ventricular arrhythmias) were also examined. Higher PV congestion index (CI) and aCWT were observed in patients with New York Heart Association (NYHA) class III/IV. Higher PVCI [hazard ratio (HR) per +1 standard deviation (SD) 1.50, p<0.01] and aCWT (HR per +1 SD 1.45, p<0.01) were independently associated with higher composite event rates during the follow-up of 122±68days. None of SMA/IMA hemodynamic parameters were associated with NYHA class or composite event rates. Higher right ventricular end-diastolic dimension (38±7 vs 34±9mm, p<0.01) and lower tricuspid annual plane systolic excursion (15±5 vs 19±5mm, p<0.001) were observed in patients with higher PVCI (>0.031cms) and aCWT (>2.8mm) relative to those in others. In conclusion, increased portal congestion and intestinal edema were associated with severe HF symptoms and poor outcomes in hospitalized HF patients, in addition to being associated with impaired right-sided cardiac function.

Serological markers “CEA test &amp; sAPRIL test” in Iraqi patients with colon cancer

Background: Colonic cancer is a very common disease world-wide being fourth most common cancer characterized by abnormal proliferation of the inner wall of colon then taking full colon wall thickness then spreading to surrounding lymph nodes and tissues and finally distant metastasis. It is one of most complicated diseases with debilitating symptoms which becomes more sever , prominent and specific with advancing stage with high percent of fatality and relatively short survival if diagnosed late or if left untreated.Objective: To evaluate the efficacy of serum CEA &amp; sAPRIL levels in the diagnosis and screening of colon cancer and their validity for this.Patients and methods: This study was applied on 35 patients with colonic cancer, 35 patients with benign polyps and 15 negative controls. All individuals were subjected to blood sampling for measuring their serum CEA &amp; sAPRIL using ELISA technique.Results: In this study, majority of patients with colon cancer were presented at ages between 53-82 years of age (mean 68.5±6.4 years). Serum levels of sAPRIL &amp; CEA were significantly elevated in those patients with advancing stages (C &amp; D) compared with stages (A &amp; B) and lower levels were found in patients who had surgical removal of tumor or received chemotherapy. Also a positive relation was found between sAPRIL &amp; CEA with alcohol intake and smokingConclusion: according to this study sample it was found that sAPRIL and CEA together are strong indicators for colon cancer screening &amp; diagnosis, and by this will reduce the need for more invasive screening &amp; diagnostic tools.&#x0D;

Primary Epiploic Appendagitis with Adjacent Colonic Wall Thickening

원발성 복막수염은 ê¸°ì €ì§ˆí™˜ 없이 복막수의 ì—¼ì „ê³¼ 주행하는 혈관의 í˜ˆì „ì— 의해 발생하며 대부분 특별한 치료 없이 수일 이내에 í˜¸ì „ëœë‹¤. 발생 빈도가 ë“œë¬¼ê³ ë¹„íŠ¹ì´ì  임상 증상을 가지므로 급성 복통의 다른 원인으로 오인되기도 한다. ë¶€ì •í™•í•œ 진단은 환자에게 불필요한 ë‚´ê³¼ì  또는 ìˆ˜ìˆ ì  치료를 받게 한다. 이를 피하기 위해 임상 의사는 이 질환을 잘 ì•Œê³ ìžˆì–´ì•¼ 하며 급성 하복부 통증으로 내원한 환자에서 ë¹„êµì  흔한 질환인 급성 게실염, 충수염과 함께 이 질환의 가능성을 염두에 ë‘ì–´ì•¼ê² ë‹¤. 과거에는 진단이 ì–´ë ¤ì› ìœ¼ë‚˜ 요즘은 복부 초음파나 ì „ì‚°í™”ë‹¨ì¸µì´¬ì˜ 등의 ì˜ìƒí•™ì  검사를 통해 진단을 내릴 수 있다. 비록 복막수는 대장벽에 ë‹¬ë ¤ 있지만 복막수염에 동반되는 대장벽 자체의 변화는 ë¹„êµì  드물다. 이에 ì €ìžëŠ” ì¸ì ‘í•œ 대장벽의 비후를 동반한 원발성 복막수염 증례를 경험하여 ë³´ê³ í•˜ëŠ” 바이다. 중심 단어: 원발성 복막수염; 대장벽의 비후; 급성 복통

Right dorsal colon ultrasonography in normal adult ponies and miniature horses.

The aim of this study was to determine the normal location, wall thickness and motility of the right dorsal colon in adult ponies and miniature horses. The abdominal ultrasonography examination was performed in a study group consisting of 23 ponies and miniature horses and in a control group comprising ten Thoroughbred horses. The procedure was performed in unsedated standing animals. The location and the thickness of the right dorsal colonic wall was examined on the right side of the abdomen between the 10th and the 14th intercostal space. The contractility was recorded in the 12th intercostal space. A comparative analysis between the study group and control group was carried out using the Student’s t-test. Pearson’s linear correlation coefficient was used to calculate the correlation between the thickness of the colonic wall as well as the number of peristaltic movements and age, wither height and body mass of the animals. The right dorsal colon was identified in all the horses in the 12th intercostal space. In all the intercostal spaces the mean ± standard deviation (SD) wall thickness of the right dorsal colon was 0.27 ± 0.03 cm in the horses from the study group and 0.37 ± 0.03 cm in the control horses. The mean number of peristaltic contractions was 4.05 ± 1.07 per minute in the animals from the study group and 1.7 ± 0.46 contractions per minute in the control group. The values of the ultrasonographic wall thickness and peristaltic motility in small breed horses in the present study were different from the values obtained for large breed horses. The study also found that the right dorsal colon in small breed horses is physiologically located in the 12th intercostal space. This suggests that different reference values should be used in small horse breeds when performing an ultrasound examination.

A Unique Triad of Ulcerative Colitis With Autoimmune Hemolytic Anemia and Primary Sclerosing Cholangitis

Inflammatory Bowel Diseases (IBD) lead to chronic intestinal inflammation along with extra-intestinal manifestations which could present prior to, subsequent with or after the diagnosis of IBD. We present a unique case of Ulcerative Colitis (UC), Autoimmune Hemolytic Anemia (AIHA) and Primary Sclerosing Cholangitis (PSC) diagnosed simultaneously in a patient. The unique triad of these diseases gives important clues to the immunological factors involved in the pathogenesis of these diseases. An 18-year-old male presented with 1 week of bloody diarrhea, abdominal cramps and nausea. Vitals were stable. Initial labs showed Hb 9.5 g/dL, MCV 102 fL, WBC 22.4 x 103/μL, total bilirubin 2.4 mg/dL, direct bilirubin 0.7 mg/dL, alkaline phosphatase 436 units/L, ALT 133 units/L and AST 83 units/L. Hepatitis panel and Clostridium difficile toxin assay were negative. Further work-up revealed reticulocyte count > 17%, LDH 529 units/L, haptoglobin < 10 mg/dl and positive direct Coomb's test. Peripheral smear showed hemolysis by a warm antibody. Hydrocortisone was started for AIHA. CT abdomen showed mild colonic wall thickening. Colonoscopy showed moderate pancolitis and biopsies showed findings consistent with UC. Mesalamine was started. MRCP showed irregular beaded appearance of intra and extrahepatic bile ducts. ERCP was performed and biopsies taken from the ducts showed chronic inflammation but no evidence of malignancy. ASMA and ANCA were positive. Liver biopsy ruled out overlap syndrome with autoimmune hepatitis. The patient clinically improved and was discharged to follow-up with a gastroenterologist. In patients with UC, extra-intestinal manifestations involving cutaneous, hepatobiliary and ocular systems are common. The concomitant presence of PSC is 2-7% and AIHA is 0.2 -1.7% in patients with UC. The extra-intestinal manifestations of UC could be due to associated autoimmune diseases or they could be immune-mediated due to damaged mucosal wall. The exact pathogenesis of PSC and AIHA is unknown. The absorption of toxins and antigenic substances from the mucosa in the circulation mediates inflammation in the biliary system leading to PSC. This also leads to warm anti-E antibody production which cross-react with intestinal microbiome and the E antigen at the surface of RBCs. In UC patients, a vigorous workup for early detection of other autoimmune diseases is important to improve the quality of life and to prevent mortality associated with them.Figure: Peripheral smear showing polychromatic RBCs and microspherocytes.Figure: Axial CT demonstrating mild wall thickening and featureless appearance of the rectosigmoid colon compatible with chronic ulcerative colitis (left). Descending colon at 4X magnification showing crypt distortion, cryptitis and crypt abscess (right).Figure: Left: Coronal thin section T2 weighted image showing a beaded appearance of the left hepatic and intrahepatic bile ducts with alternating strictures (arrows) and dilatation (arrowheads). Right: A) Fluoroscopic image from an ERCP depicting beading of the bilateral intrahepatic bile ducts due to segmental strictures (thin arrows). Guidewire in the left intrahepatic bile duct (thick arrow). B) ERCP image after biliary stent placement (arrowhead) with decompression of the biliary tree.

Recurrent Mantle Cell Lymphoma Presenting as Colonic Mass

Mantle cell lymphoma (MCL) is a rare and aggressive subtype of B cell Non-Hodgkin's Lymphoma. MCL frequently involves extranodal sites and gastrointestinal tract is involved in 80% of cases. MCL is usually resistant to standard chemotherapy regimens and associated with high recurrence rate. Recurrent disease is very aggressive and resistant to treatment. We present a case of recurrent MCL involving the colon despite intensive chemotherapy. A 58 year old woman presented to our hospital with complaints of left sided abdominal pain and hematochezia since one day. Abdominal pain was described as severe and continuous with no radiation. She was diagnosed with MCL two years ago when she had axillary lymph node biopsy. She was treated with standard chemotherapy regimen and stem cell transplantation at that time. She had a relapse one year after initial treatment for which she was again treated with chemotherapy. On examination, no lymphadenopathy was noted. Abdominal examination was significant for left lower quadrant tenderness without guarding, rigidity or hepatosplenomegaly. Laboratory tests were normal. Computed tomography scan of abdomen showed ascending colon wall thickening. Colonoscopy showed mass like lesion in the ascending colon and polyps in the ascending colon as well as splenic flexure. The biopsy of all the three lesions showed atypical lymphocytes infiltrating the lamina propria. The tumor cells were positive for cyclin-D1, CD 5, CD 20, CD 43 and CD 79A consistent with the diagnosis of MCL. Patients with MCL and gastrointestinal involvement could be asymptomatic or may present with abdominal pain, obstruction, diarrhea, or hematochezia. The most common site of involvement in the GI tract is ileocecal region, but any other area may be involved from the stomach to the rectum. Involvement of the gastrointestinal tract may occur with or without the appearance of polyps. Even though there are no standard guidelines for endoscopic screening of gastrointestinal tract in asymptomatic patients, one should be aware of involvement of gastrointestinal tract in the early course of disease or recurrent disease. Although mantle cell lymphoma is initially responsive to chemotherapy, it eventually becomes refractory with median survival of 3 to 5 years. Patients with obstructive tumor masses require surgical therapy, but the mainstay of treatment is chemotherapy.Figure: A polypoid non-obstructing medium-sized mass. Polyp with normal looking mucosa was found at the splenic flexure.Figure: A frond-like/villous, fungating, infiltrative, polypoid and ulcerated nonobstructing large mass was found in the ascending colon.

Recurrence of Colonic Diverticulitis: Identifying Predictive CT Findings-Retrospective Cohort Study.

Purpose To identify computed tomographic (CT) findings that are predictive of recurrence of colonic diverticulitis. Materials and Methods Institutional review board approval was obtained for this HIPAA-compliant, retrospective cohort study. Six abdominal fellowship-trained radiologists reviewed the CT studies of 440 consecutive subjects diagnosed with acute colonic diverticulitis between January 2004 and May 2008 to determine the involved segments, maximum wall thickness in the inflamed segment, severity of diverticulosis, presence of complications (abscess, fistula, stricture, or perforation), and severity of the inflammation. Electronic medical records were reviewed for a 5-year period after the patients' first CT study to determine clinical outcomes. Predictors of diverticulitis recurrence were assessed with univariate and multiple Cox proportional hazard regression models. Results Colonic diverticulitis most commonly involved the rectosigmoid (70%, 309 of 440) and descending (30%, 133 of 440) colon segments. Complicated diverticulitis was present in 22% (98 of 440) of patients. On the basis of the results of univariate analysis, significant predictors of diverticulitis recurrence were determined to be maximum colonic wall thickness in the inflamed segment (hazard ratio [HR], 1.07 per every millimeter of increase in wall thickness; P < .001), presence of a complication (HR, 1.75; P = .002), and subjective severity of inflammation (HR, 1.36 for every increase in severity category; P value for linear trend = .003). The difference in maximum wall thickness in the inflamed segment (HR, 1.05 per millimeter; P = .016) and subjective inflammation severity (HR, 1.29 per category; P = .018)remained statistically significant in a Cox multiple regression model. Conclusion Maximum colonic wall thickness and subjective severity of acute diverticulitis allow prediction of recurrent diverticulitis and may be useful for stratifying patients according to the need for elective partial colectomy. © RSNA, 2017 Online supplemental material is available for this article.

69-Year-Old Man With Abdominal Pain and Obstipation

69-Year-Old Man With Abdominal Pain and Obstipation

New Peptide Inhibitor of Dipeptidyl Peptidase IV, EMDB-1 Extends the Half-Life of GLP-2 and Attenuates Colitis in Mice after Topical Administration.

Protease inhibition has become a possible new approach in inflammatory bowel disease (IBD) therapy. A serine exopeptidase, dipeptidyl peptidase IV (DPP IV), is responsible for the inactivation of incretin hormone, glucagon-like peptide 2 (GLP-2), a potent stimulator of intestinal epithelium regeneration and growth. Recently, we showed that the novel peptide analog of endomorphin-2, Tyr-Pro-D-ClPhe-Phe-NH2 (EMDB-1) is a potent blocker of DPP IV and has an inhibitory effect on gastrointestinal (GI) smooth muscle contractility. The aim of this study was to characterize the anti-inflammatory effect and mechanism of action of EMDB-1 in the mouse GI tract. We used two models of experimental colitis (induced by TNBS and DSS). The anti-inflammatory effect of EMDB-1 was assessed by the determination of macroscopic score, ulcer score, colonic wall thickness, as well as myeloperoxidase activity. Additionally, we measured the expression of GLP-2, GLP2R, and DPP IV in the colon of control and colitic animals treated with the test compound. The expression of GLP-2 and GLP2R in the serum and colon of IBD patients and healthy control subjects has been assessed. We showed that EMDB-1 elevates the half-life of GLP-2 in vitro and attenuates acute, semichronic, and relapsing TNBS as well as DSS-induced colitis in mice after topical administration. The anti-inflammatory action of EMDB-1 is associated with changes in the level of colonic GLP-2 but not DPP IV expression. Our results validate DPP IV as a pharmacological target for the anti-IBD drugs, and its inhibitors based on natural substrates, such as EMDB-1, have the potential to become valuable anti-inflammatory therapeutic agents.

THE CASE FILES

THE CASE FILES

The value of serological markers (CA19-9 &amp; CCSA4) in the screening and prognosis of colon cancer

Background:- Colonic cancer is a very common disease world-wide being fourth most common cancer characterized by abnormal proliferation of the inner wall of colon at beginning then taking full colon wall thickness then to surrounding lymph nodes and tissues and finally metastasis.Objective:- To evaluate the efficacy of serum CA19-9 and CCSA-4 levels in the screening and prognosis of colonic cancer and their validity for this.Patients and methods:-This study was applied on 35 patients with colonic cancer, 35 patients with benign polyps and 16 negative controls. All individuals were subjected to blood sampling for measuring their serum CA19-9 and CCSA-4 using ELISA technique.Results:-Our study shows that colonic cancer patients presented at ages between 53-82 years of age (mean 68.5). Serum levels of CCSA-4 were significantly elevated in those patients with advancing stages (C&amp;D) compared with stages (A&amp;B) and lower levels found in patients undergone surgical removal of tumor or received chemotherapy.Also a positive relation found between CCSA-4 with alcohol intake and smoking. Less significant levels and relations found with CA19-9.Conclusion:-Serum CCSA-4 is sensitive and specific indicator for diagnosis, prognosis and screening of colonic cancer.

Systemic Administration of Sialorphin Attenuates Experimental Colitis in Mice via Interaction With Mu and Kappa Opioid Receptors.

Pharmacological treatment and/or maintenance of remission in inflammatory bowel disease [IBD] is currently one of the biggest challenges in the field of gastroenterology. Here we aimed to assess the anti-inflammatory effect and the mechanism of action of sialorphin, the natural blocker of the endogenous opioid peptide-degrading enzymes neprilysin [NEP] and aminopeptidase N [APN], in mouse models of IBD and the changes in the expression of these enzymes in IBD patients. We used two models of experimental colitis in mice [2,4,6-trinitrobenzene sulphonic acid [TNBS]- and dextran sulphate sodium [DSS]-induced]. Macroscopic score, ulcer score, colonic wall thickness, and myeloperoxidase [MPO] activity were recorded. Additionally, we measured the expression of NEP and APN in the colon of IBD patients and healthy controls. We showed that sialorphin attenuated acute, semichronic, and relapsing TNBS-induced colitis in mice after systemic administration, and its anti-inflammatory action is associated with mu and kappa opioid receptors. We show that indirect stimulation of opioid receptors by the blockade of NEP and APN is a promising pharmacological strategy for the treatment of IBD, and may become of greater importance than the use of classical opioid agonists.

SPECT-computed tomography in rats with TNBS-induced colitis: A first step toward functional imaging.

AIMTo assess the feasibility of SPECT-computed tomography (CT) in rats with trinitrobenzene sulfonic acid (TNBS)-induced acute colitis and confront it with model inflammatory characteristics.METHODSColitis was induced in Sprague-Dawley rats by intrarectal injection of TNBS (n = 10) while controls received vehicle (n = 10). SPECT-CT with intravenous injection of 10 MBq of 67Ga-Citrate was performed at day 2. SPECT-CT criteria were colon wall thickness and maximal wall signal intensity. Laboratory parameters were assessed: colon weight:length ratio, colon cyclooxygenase-2 expression by western blot and histological inflammatory score.RESULTSColon weight/length ratio, colon COX-2 expression and histological inflammatory score were significantly higher in the TNBS group than in the control group (P = 0.0296, P < 0.0001, P = 0.0007 respectively). Pixel max tend to be higher in the TNBS group than in the control group but did not reach statistical significance (P = 0.0662). Maximal thickness is significantly increased in the TNBS group compared to the control group (P = 0.0016) while colon diameter is not (P = 0.1904). Maximal thickness and colon diameter were correlated to colon COX-2 expression (P = 0.0093, P = 0.009 respectively) while pixel max was not (P = 0.22). Maximal thickness was significantly increased when inflammation was histologically observed (P = 0.0043) while pixel max and colon diameter did not (P = 0.2452, P = 0.3541, respectively).CONCLUSIONSPECT-CT is feasible and easily distinguished control from colitic rats.

Invasive Moderately-Differentiated Mucinous Adenocarcinoma Incidentally Identified in Perforated Acute Diverticulitis With Abscess Formation

Colonic adenocarcinoma rarely arises within a diverticulum. As illustrated in this case report, such an occurrence presents difficulties in diagnosis, posed by the overlap of radiological findings in diverticulitis and adenocarcinoma and the potential absence of luminal lesion. Here we present a 77-year-old male with acute left lower abdominal pain, fever and leukocytosis. Computarized tomography (CT) imaging revealed extensive colonic diverticulosis, with sigmoid colon wall thickening, extraluminal air and a pericolic abscess. No enlarged lymph nodes were detected. The clinical diagnosis was acute sigmoid diverticulitis with micro-perforation and abscess formation. Partial sigmoidectomy was performed and diverticulitis confirmed; no tumor was identified in the resected colon. However, fragments of mucinous adenocarcinoma were incidentally recognized in the pericolic abscess contents. Immunohistochemical (IHC) studies supported a primary colonic adenocarcinoma, warranting further clinical workup. A subsequent distal sigmoidectomy revealed moderately-differentiated mucinous adenocarcinoma invading through the visceral peritoneum, and arising in a low-grade mucinous neoplasm within a diverticulum. The case illustrates that in a patient with diverticulitis and no evidence of a luminal neoplasm, the unexpected finding of adenocarcinoma in the resected bowel may be attributable to adenocarcinoma arising within a diverticulum.

Prognostic impact of intestinal wall thickening in hospitalized patients with heart failure

BackgroundIntestine-cardiovascular relationship has been increasingly recognized as a key factor in patients with heart disease. We aimed to identify the relationships among intestinal wall edema, cardiac function, and adverse clinical events in hospitalized heart failure (HF) patients. Methods and resultsAbdominal computed tomographic images of 168 hospitalized HF patients were retrospectively investigated for identification of average colon wall thickness (CWT) from the ascending to sigmoid colon. Relationships between average CWT and echocardiographic parameters, blood sampling data, and primary outcomes including readmission for deteriorated HF and all-cause mortality were evaluated. Among the echocardiographic parameters, lower left ventricular diastolic function was correlated with higher average CWT. In multivariate analysis, higher logarithmic C-reactive protein level, lower estimated glomerular filtration rate, lower peripheral blood lymphocyte count, higher E/E′ ratio, and extremely higher/lower defecation frequency were independently correlated with higher average CWT. Multivariate Cox-hazard analysis demonstrated that higher average CWT was independently related to higher incidence of primary outcomes. ConclusionIn hospitalized HF patients, increased CWT was associated with lower cardiac performance, and predicted poorer long-term clinical outcomes.