Clin Gastroenterol Research Articles

The Colon Adenoma-Carcinoma Paradox in Women: Role of Transforming Growth Factor (TGF)β Signaling

Purpose: Colorectal cancer (CRC) effects both genders roughly equally, being the third leading cause of cancer deaths in both women and men. However, emerging evidence indicates that adenomas may be much less frequent in women than men (e.g., Regula et al., NEJM 2006, Nguyen et al., Clin Gastroenterol Hepatol. 2009). The lower adenoma yet approximately equivalent CRC rate has been termed the “women's CRC paradox”. This suggests decreased initiation and enhanced progression phases of colon carcinogenesis in women. From a molecular perspective, this effect appears to be pathognomonic for TGF β which acts as a tumor suppressor in early lesions and a proto-oncogene in more advanced lesions. Moreover, in the colon TGF β appears to be controlled by estrogen receptor β, providing a potential gender-specific link. In this study, we wanted to confirm the paradox in a well-defined dataset and assess TGF β role via activity detected through its surrogate marker, phospho-SMAD2/3. Methods: We queried our CRC translational research database to identify unselected patients with CRC resections and colonoscopy from 2006-2009. For tissue analysis, we assessed biopsies of uninvolved rectum from our pathology repository. Immunohistochemistry (IHC) were performed using standard techniques with a monoclonal antibody to phosphorylated SMAD 2/3(Cell Signaling, MA) and nuclear staining was scored by a GI pathologist blinded to gender. Results: Our cohort consisted of 130 patients with CRC and 1159 with colonoscopy for adenoma detection. As noted in figure 1, the number of CRCs were comparable between males and females. On the other hand, women had 64.9% of the number of total adenomas in men (p<0.01). Women also had a 36.2% decrease in advanced adenomas(p<0.01). Nuclear phospho-SMAD 2/3 was markedly elevated in the endoscopically-normal rectal mucosa of women and this 54% increase was highly statistically significant (p<0.001).FigureConclusion: We confirm the gender “paradox” with women having equal number of cancers but half the adenomas prevalence of men. Furthermore, we make the novel observation that women appear to have more marked TGF β signaling (gauged by phospho-SMAD 2/3) providing a biologically plausible mechanism for the “paradox”. Future studies will address the clinical consequences and biological underpinnings of this phenomena.

Biliary and pancreatic stone extraction devices

Biliary and pancreatic stone extraction devices

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The following reply refers to a letter to the editor (Reiss G, Ramrakhiani S. Right upper-quadrant pain and a normal abdominal ultrasound. Clin Gastroenterol Hepatol 2009;7:603) published in the May 2009 issue of Clinical Gastroenterology and Hepatology.

0023: Modern Imaging Approach to Pancreatic Tumours

Endoscopic ultrasound (EUS) is the most sensitive technique for the detection and more importantly for the exclusion of ductal adenocarcinoma of the pancreas. In addition, ultrasound, EUS and sophisticated computed tomography techniques represent nowadays the standard techniques for evaluation of pancreatic disease including staging [J Cancer Res Clin Oncol 2008; 134:635-643. Clin Gastroenterol Hepatol 2008; 6:590-597]. With proof of a definite pancreatic tumour and urgent suspicion of a ductal adenocarcinoma of the pancreas without distant metastasis and option of curative surgery, an operation is primarily indicated. However, this does not mean that each pancreatic mass should unreflected undergo surgery. but the options of the preoperative imaging must be exhausted. In discrepancy to formerly published statements that 95 % of all pancreatic tumours are ductal adenocarcinoma it could be shown that in specialized centers up to 50 % of these masses are other tumour entities. Thus, it is of crucial importance to clarify the dignity of such a mass preoperatively, since a significant operation lethality has to be considered. The quality of the preoperative diagnostics of an interdisciplinary center can also be rated on the basis of preoperative correctly identified diagnoses. This is in particular true for the asymptomatic serous microcystic pancreatic adenoma representing no indication for surgery and autoimmune pancreatitis which should be treated by immunosuppression. In addition, differentiated neuroendocrine tumours should be enucleated preserving pancreatic tissue and should not undergo radical operation technique. Endoscopic ultrasound (EUS) is the most sensitive technique for the detection and more importantly for the exclusion of ductal adenocarcinoma of the pancreas. In addition, ultrasound, EUS and sophisticated computed tomography techniques represent nowadays the standard techniques for evaluation of pancreatic disease including staging [J Cancer Res Clin Oncol 2008; 134:635-643. Clin Gastroenterol Hepatol 2008; 6:590-597]. With proof of a definite pancreatic tumour and urgent suspicion of a ductal adenocarcinoma of the pancreas without distant metastasis and option of curative surgery, an operation is primarily indicated. However, this does not mean that each pancreatic mass should unreflected undergo surgery. but the options of the preoperative imaging must be exhausted. In discrepancy to formerly published statements that 95 % of all pancreatic tumours are ductal adenocarcinoma it could be shown that in specialized centers up to 50 % of these masses are other tumour entities. Thus, it is of crucial importance to clarify the dignity of such a mass preoperatively, since a significant operation lethality has to be considered. The quality of the preoperative diagnostics of an interdisciplinary center can also be rated on the basis of preoperative correctly identified diagnoses. This is in particular true for the asymptomatic serous microcystic pancreatic adenoma representing no indication for surgery and autoimmune pancreatitis which should be treated by immunosuppression. In addition, differentiated neuroendocrine tumours should be enucleated preserving pancreatic tissue and should not undergo radical operation technique.

Society of Interventional Radiology Position Statement on Chemoembolization of Hepatic Malignancies

Society of Interventional Radiology Position Statement on Chemoembolization of Hepatic Malignancies

A New Answer to an Old Question: Azathioprine Withdrawal in Quiescent Crohn's Disease

A New Answer to an Old Question: Azathioprine Withdrawal in Quiescent Crohn's Disease

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Kisiel et al have identified key issues raised by our study and surrounding computed tomographic colonography (CTC) use, and seem to project an optimistic perspective that CTC use will not be associated with problems in these areas. My perspective is simply that neither optimism nor pessimism is justified in the absence of data, and that we should understand the range of potential outcomes with regard to CTC use. Our study demonstrated that widespread use of CTC in place of colonoscopy would result in a major paradigm shift in management of patients with only small polyps. The bulk of patients we identified with “high risk adenoma findings” that would have normal CTC reports were patients with ≥3 adenomas all of which were ≤5 mm in size and no polyp of any histology ≥6 mm in size. We acknowledged a critical lack of understanding of whether these patients are really at risk of metachronous advanced neoplasm (Ann Intern Med 2008;148:419–426). If they are at increased risk, it could be because this finding is a marker of missed advanced neoplasia, missed flat adenomas, incomplete polypectomy, or a marker of a field defect that predicts increased risk of metachronous advanced neoplasia. The issue is critical to CTC use, and it is important to acknowledge that it is a patient-based issue (Are patients with multiple adenomas at increased risk of metachronous advanced neoplasms?) more than an issue of the natural history of individual adenomas ≤5 mm in size. There are currently insufficient data to resolve the issue. Second, models other than those quoted by Kiesel et al have suggested that the C-RADS recommendation of CTC surveillance for 1 or 2 polyps 6–9 mm in size (and with no large polyp) could result in a substantial increase in colorectal cancer incidence and death (Clin Gastroenterol Hepatol 2007;5:237–244). The CT Colonography Reporting and Data System (C-RADS) language suggesting a stronger rationale for removing 6- to 9-mm polyps in younger persons makes sense with regard to life-years saved when cancer is prevented, but fails to recognize that, biologically, such lesions in older persons may be substantially more likely to become cancer within any given time interval (Gut 2007;56:1585–1589). Finally, I agree that nothing is more pertinent to colorectal cancer prevention than improving adherence to screening tests. I prefer, though, to see some evidence that CTC will substantially increase adherence (Am J Gastroenterol 2004;99:1145–1151). Increased adherence through CTC would clearly prevent colorectal cancers. If CTC simply displaces patients from colonoscopy then the outcomes are much more uncertain (Clin Gastroenterol Hepatol 2008;6:506–514). Computed Tomographic Colonography and High-Risk Adenomas: A Gap in the Guidelines?GastroenterologyVol. 136Issue 7PreviewRex DK, Overhiser AJ, Chen SC, et al. (Division of Gastroenterology, Indiana University Medical Center, Indianapolis, Indiana.) Estimation of impact of American College of Radiology Recommendations on CT colonography reporting for resection of high-risk adenoma findings. Am J Gastroenterol 2009;104:149–153. Full-Text PDF

S1264 Anal Electrical Stimulation Increases Anal Sphincter Pressure in Healthy Subjects

ation of reduced pain thresholds and a history of frequent visceral pain (Rome III questionnaire: question 42). Conclusion: In this patient population, IBS with or without painpredominance as diagnosed by Rome III criteria was not associated with VH as defined by reduced pain thresholds during rectal barostat distension. These findings suggest that 1) Rome III criteria might identify different patients than the former Rome II criteria; and/or that 2) the contribution of VH to the pathogenesis of pain in IBS may be smaller than hitherto assumed. Indeed, the latter hypothesis is supported by a recent study detecting VH in only 21% of IBS (Rome II) patients [2]. Provided our observations are confirmed in a larger trial including both healthy and specific disease control subjects, the pathogenic role and diagnostic value of VH in IBS need be re-considered. 1. Bouin et al. Gastroenterology 2002;122:1771-1777 2. Camilleri et al. Clin Gastroenterol Hepatol 2008;6:772-781

363 Post-Infective Dyspepsia Eight Years After the Walkerton Outbreak of Waterborne Gastroenteritis (GE)

prevalence study. As part of our initial protocol, multiple biopsies were obtained from esophagus, stomach and duodenum on each patient. Non-ulcer dyspepsia patients were identified via a detailed chart review strictly using Rome III criteria for non-ulcer dyspepsia. A blinded pathologist counted eosinophils in 5 high-power fields in both the stomach and duodenum. The presence of eosinophil clusters, eosinophil degranulation and Helicobacter pylori were also collected. Results: 93.5% (374/400) patients completed endoscopy with biopsies. The group had a mean age (SD) of 52(15) years, 51% male and 56% Caucasian. 28.3% (106/374) of patients met criteria for non-ulcer dyspepsia. Mean (SD) eosinophil count in the proximal and distal esophagus, stomach and duodenum were 0.96 (5.3), 0.99 (6.7), 5.3 (8.6) and 20.5 (10.3), respectively. When comparing patients with non-ulcer dyspepsia versus all other patients, there was no difference in mean gastric (5.4 vs. 5.2, p = 0.81) or duodenal eosinophil count (19.8 vs. 20.8, p=0.41). There was no increased frequency of eosinophil degranulation, eosinophil clusters or Helicobacter pylori in patients with nonulcer dyspepsia. Patients with Helicobacter pylori (N=46) had a higher mean gastric (10.6 vs. 4.5, p<0.001) and duodenal eosinophil count (24.3 vs. 20.0, p=0.01) compared to patients who were Helicobacter pylori negative. Conclusion: Amongst patients undergoing outpatient upper endoscopy, there was no difference in mean stomach or duodenum eosinophil count between patients with and without non-ulcer dyspepsia. Only Helicobacter pylori was associated with elevated eosinophil counts in stomach and duodenum. Further studies are need to determine the role of gastric and duodenal eosinophilia as biomarkers for nonulcer dyspepsia.

Review: Interferon and nucleoside/tide analogues reduce risk for hepatocellular cancer in patients with chronic hepatitis B

ACP Journal Club21 April 2009Review: Interferon and nucleoside/tide analogues reduce risk for hepatocellular cancer in patients with chronic hepatitis BAverell H. Sherker, MD, FRCP(C)Averell H. Sherker, MD, FRCP(C)Washington Hospital Center and Georgetown University, Washington, DC, USA (A.H.S.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-150-8-200904210-02011 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Source CitationSung JJ, Tsoi KK, Wong VW, Li KC, Chan HL. Meta-analysis: Treatment of hepatitis B infection reduces risk of hepatocellular carcinoma. Aliment Pharmacol Ther. 2008;28:1067-77. https://pubmed.ncbi.nlm.nih.gov/18657133Clinical Impact RatingsGastroenterology: Infectious Disease: References1 Keeffe EB, Dieterich DT, Han SH, et al. A treatment algorithm for the management of chronic hepatitis B virus infection in the United States: 2008 update. Clin Gastroenterol Hepatol. 2008;6:1315-41. [PMID: 18845489] Google Scholar2 Bruix J, Sherman M, Practice Guidelines Committee, American Association for the Study of Liver Diseases. Management of hepatocellular carcinoma. Hepatology. 2005;42:1208-36. [PMID: 16250051] Google Scholar Author, Article, and Disclosure InformationAuthors: Averell H. Sherker, MD, FRCP(C)Affiliations: Washington Hospital Center and Georgetown University, Washington, DC, USA (A.H.S.)This article was published at Annals.org on 7 April 2009. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 21 April 2009Volume 150, Issue 8Page: JC4-11KeywordsCancer preventionCancer treatmentChronic hepatitis BCirrhosisCohort studiesInfectious diseasesInfectious hepatitisInterferonsLiver transplantationTreatment guidelines ePublished: 21 April 2009 Issue Published: 21 April 2009 Copyright & PermissionsCopyright © 2009 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...

Chromoendoscopy with Water Infusion Colonoscopy in Detecting Colonic Lesions

Background: Water infusion in lieu of air insufflation colonoscopy achieves high cecal intubation rate; the cleansing effect of water improves identification of mucosal pathologies. Aim: To determine the feasibility of combining chromoendoscopy with water infusion colonoscopy in detecting colonic lesions. Method: Water infusion colonoscopy was performed with warm water (37°C) containing 0.005% Methylene blue (MB). Air was turned off until the cecum was reached and appendix opening identified under water. Air was then insufflated and fluid suctioned on scope withdrawal to aid examination and removal of lesions. Bowel preparation was rated good (3), fair (2), poor (1) on scope insertion. Results: 50 unselected patients underwent screening colonoscopy using the MB water infusion technique. Cecal intubation rate was 100%. Bowel preparation quality was fair [mean score 2.1 (SD 0.4)]. Neoplastic polyps were identified in 23 patients (46%). A total of 50 adenomas were identified: cecum (3), ascending (19), transverse (8), descending (10), sigmoid (5) and rectum (5). One adenoma had high grade dysplasia. The size distribution of the adenomas was: <6 mm (18), 6-9 mm (15), ≥10 mm (17). A total of 72 non-neoplastic lesions were identified: hyperplastic polyps (56), no specific abnormalities (16). Total withdrawal time was 15.6 (SD 6.6) minutes. Total procedure time was 27.9 (SD 9.5) minutes. The blue color water did not impair examination although a green color change of the fluid indicated fair to poor prep from residual stool. There were no significant complications (1 patient had transient passage of green urine). Conclusions: Chromoendoscopy added to the water infusion technique is feasible. Compared to historical adenoma detection rate of air insufflation colonoscopy [38% (JAMA 2008;299: 1027) and 42% (NEJM 2000;343: 162)], the current report had a numerically higher neoplastic polyp pick up rate of 46%. The cleansing effect coupled with dye staining may have enhanced the detection of adenomas. Conventional targeted chromoendoscopy requires up to an average of 33 minutes in total procedure time (JAMA 2008;299: 1027). Withdrawal time for conventional pancolonic chromoendoscopy requires up to an average of 26 minutes (Clin Gastroenterol Hepatol 2006;4: 349). The current method offers shorter procedure time compared with the traditional method of spraying of the mucosa with the chromoendoscopy dye. Compatibility with conventional colonoscope also minimizes set up cost for this novel combination. Table 1 Withdrawal time (min.)/ Total procedure time (min.) 15.6 (SD 6.6)/ 27.9 (SD 9.5) Neoplastic polyps pick up rate 46% Number of lesions indentified/Neoplastic/Non-neoplastic 122/50/72 Open table in a new tab

Three synchronous gastrointestinal tumours

Mucinous cystadenomas of the appendix are rare, with significant malignant potential [Lo and Sarr in Hepatogastroenterology 50(50):432-437, 2003]. Carcinoid tumours are similarly uncommon, rarely occurring in Meckel's diverticula but are still the commonest tumour of Meckel's diverticulae [Nies et al. in Dis Colon Rectum 35(6):589-596, 1992; Modlin and Lye in Cancer 97(4):934-959, 2003; Sutter et al. in Schweiz Med Wochenschr Suppl 89:20S-24S, 1997; Weber and McFadden DW in J Clin Gastroenterol 11(6):682-686, 1989]. A 77-year-old woman presented to our clinic with a 6-week history of non-specific lower abdominal pain. A pelvic ultrasound showed an 8 × 3 × 2.5 cm mass in the right iliac fossa. Colonoscopy and CT confirmed this mass and also revealed a left colonic tumor. At laparotomy, three tumours were identified; in the appendix, a Meckel's diverticulum, and the descending colon. A subtotal colectomy and diverticulectomy were performed. Histology confirmed a T3N0 Dukes B colonic adenocarcinoma, a carcinoid of Meckel's diverticulum and a mucinous adenoma of the appendix. The patient is tumor free to date, 5 years after presentation. The presence of three synchronous tumours of different histological origin in the gastrointestinal tract has not previously been described in the literature.

Human NOTES Cholecystectomy: Transgastric Hybrid Technique

BackgroundNatural orifice translumenal endoscopic surgery (NOTES) is an emerging field in minimally invasive surgery that is driving the development of new technology and techniques. There are several proposed benefits to the NOTES approach, including potentially decreased abdominal pain, wound infections, and hernia formation Ko and Kalloo (Chin J Dig Dis 7:67–70, 2006); Wagh et al. (Clin Gastroenterol Hepatol 3(9):892–896, 2005); ASGE/SAGES Working Group on Natural Orifice Transluminal Endoscopic Surgery (Gastrointest Endosc 63(2):199–203, 2006); and Pearl and Ponsky (J GI Surg 12:1293–1300, 2008). Cholecystectomy has been one of the most commonly performed NOTES procedures to date, with the majority being performed through the transvaginal approach Marescaux et al. (Arch Surg 142:823–826, 2007); Zorron et al. (Surg Endosc 22:542–547, 2008); and Ramos et al. (Endoscopy 40:572–575, 2008). Transgastric approaches for cholecystectomy have been shown to be technically feasible in animal models and in several unpublished human patients Sumiyama et al. (Gastrointest Endosc 65(7):1028–1034, 2007). This video demonstrates the technique by which we perform transgastric NOTES hybrid cholecystectomy in human patients. MethodPatients with symptomatic gallstone disease are enrolled under an IRB approved protocol. A diagnostic EGD is performed to confirm normal anatomy. Peritoneal access is gained using a needle-knife cautery and balloon dilation under laparoscopic visualization. Dissection of the critical view of safety is performed endoscopically. The cystic duct and artery are clipped laparoscopically and the gallbladder is dissected off of the liver. The gastrotomy is closed intralumenally and over-sewed laparoscopically. The gallbladder is extracted out the mouth. ResultsThis technique was used to successfully perform four NOTES hybrid transgastric cholecystectomies without operative complications. ConclusionsNOTES hybrid transgastric cholecystectomy can be performed safely in human patients. This procedure is still technically challenging given the current instrumentation that is available. In order to perform a pure NOTES transgastric cholecystectomy, a safe blind access method, improved retraction, endoscopic hemostatic clips, and reliable closure methods need to be developed.

GERD and the Effect of Metabolic Risk Factors

Recent data suggest that the prevalence of gastroesophageal reflux disease in the U.S. is increasing by 5% annually (Clin Gastroenterol Hepatol 2007; 5:17). Although GERD has a substantial effect on public health, the natural course of this disorder is not well defined. To examine the effect of metabolic risk factors on the natural course of GERD, researchers analyzed data on 3669 patients in Taiwan who, as part of a voluntary health-promotion program, underwent upper gastrointestinal endoscopy at least twice …

Clinical Challenges and Images in GI

Question: A 63-year-old man with no significant medical history presented with obscure abdominal discomfort. He underwent computed tomography (Figure A), which revealed a mass in the pelvic cavity. The mass was a smooth-surfaced, egg-shaped lesion with a central low-density area. Magnetic resonance imaging was performed to confirm the finding (Figure B). T1-weighted images showed a low-intensity mass with a central high-intensity area. The mobile, hard mass was palpable by digital examination; however, colonoscopy revealed normal rectal mucosa and no submucosal tumor. Further physical examination and laboratory investigations showed normal findings. What is the diagnosis?View Large Image Figure ViewerDownload Hi-res image Download (PPT) Look on page 730 for the answer and see the Gastroenterology website (www.gastrojournal.org) for more information on submitting your favorite image to Clinical Challenges and Images in GI. Pelvic CT scan showed a 45- × 40-mm mass and MRI demonstrated a low-intensity mass. In both investigations, the mass was found to show the same degree of intensity as the surrounding muscle tissue. A high-intensity area was observed in the center of the mass, identical to that seen in fatty tissues. The patient underwent laparoscopic surgery. We found a hard, white, egg-shaped peritoneal loose body that was completely free in the pelvic cavity (Figure C). The mass was laparoscopically removed using an endopouch. It was composed of many layers of laminated, fibrous tissues surrounding a central necrotic fatty lesion (Figure D). This mass was a “peritoneal loose body” as defined by the intraperitoneal separate body, which was mainly made from protein and calcium phosphate.View Large Image Figure ViewerDownload Hi-res image Download (PPT) The general conception of peritoneal loose bodies is that they arise owing to torsion and separation of the appendices epiploicae, which are visceral peritoneal pouches filled with fat that exist along the antimesenteric tenia of the colon. It is important to differentiate peritoneal loose bodies from other lesions such as gastrointestinal stromal tumors (GIST), fibromas, desmoid tumors, teratomas, and urinary, gallbladder, and appendix stones. GIST is especially hard to distinguish from peritoneal loose bodies; however, the former exhibits a contrast-enhancing effect unlike peritoneal loose bodies, which require additional prone-positioned computed tomography examinations to monitor their mobility. A huge peritoneal loose body (∼10 cm) has been reported previously.1Mohri T. Kato T. Suzuki H. A giant peritoneal loose body: report of a case.Am Surg. 2007; 73: 895-896PubMed Google Scholar Such loose bodies rarely cause any symptoms if they are small (0.5–2.5 cm in diameter); however, “giant” peritoneal loose bodies (>5 cm in diameter) present with various symptoms.2Ghosh P. Strong C. Naugler W. et al.Peritoneal mice implicated in intestinal obstruction: report of a case and review of the literature.J Clin Gastroenterol. 2006; 40: 427-430Crossref PubMed Scopus (29) Google Scholar, 3Bhandarwar A.H. Desai V.V. Gajbhiye R.N. et al.Acute retention of urine due to a loose peritoneal body.Br J Urol. 1996; 78: 951-952Crossref PubMed Google Scholar If CT or MRI images reveal a huge peritoneal loose body, laparoscopic surgery is indicated, unlike cases that show small loose bodies.4Nomura H. Hata F. Yasoshima T. et al.Giant peritoneal loose body in the pelvic cavity: report of a case.Surg Today. 2003; 33: 791-793Crossref PubMed Scopus (25) Google Scholar In this case, abdominal discomfort disappeared spontaneously before operation. Therefore, we believe only symptomatic or cases that have significant findings should be treated surgically.

The Cure(s) of LOTUS

The Cure(s) of LOTUS

You See UC: An Animal Model of Ulcerative Colitis

You See UC: An Animal Model of Ulcerative Colitis

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Should Surgery Replace Pneumatic Dilation in Achalasia?

Should Surgery Replace Pneumatic Dilation in Achalasia?

Ulcerative Colitis and Crohn's Disease Genetics: More Similar Than We Thought?

Ulcerative Colitis and Crohn's Disease Genetics: More Similar Than We Thought?