Colon Cancer at Molecular Level : Cancer Prevention in Patients with Inflammatory Bowel Disease

( Steven H. Itzkowitz ) 대한소화기학회 2003 SIDDS Vol.7 No.-

REVIEW : Stool DNA Testing for Colorectal Cancer: Development and Advances

( Steven H. Itzkowitz ) 대한장연구학회 2012 Intestinal Research Vol.10 No.2

Screening for colorectal cancer is one of the most effective public health interventions. Although colonoscopy is the preferred method in many settings, colonoscopy can miss lesions, interval neoplasms can arise after a normal colonoscopy, and some patients refuse to undergo colonoscopy. In the last decade, detection of neoplasia-associated genetic alterations in the stool has become feasible. First-generation stool DNA tests demonstrated better sensitivity for colorectal cancer than fecal occult blood tests. Improvements to stool DNA tests have made them more sensitive and less complex. The newer marker panels can detect colorectal cancer and even the majority of advanced adenomas, regardless of location in the colon. This review summarizes the development and advances to stool DNA testing for colorectal cancer. (Intest Res 2012;10:134-141)

Review : Colorectal Cancer in Inflammatory Bowel Disease

( Jonathan Potack ),( Steven H. Itzkowitz ) The Editorial Office of Gut and Liver 2008 Gut and Liver Vol.2 No.2

Patients with long-standing inflammatory bowel disease have an increased risk of developing colorectal cancer (CRC). CRC risk increases with longer duration of colitis, greater anatomic extent of colitis, the presence of primary sclerosing cholangitis, family history of CRC and severity of inflammation of the colon. Chemoprevention includes aminosalicylates, ursodeoxycholic acid, and possibly folic acid. To reduce CRC mortality in IBD, colonoscopic surveillance remains the major way to detect early mucosal dysplasia. When dysplasia is confirmed, proctocolectomy is considered for these patients. Ulcerative colitis patients with total proctocolectomy and ileal pouch anal-anastomosis have a rather low risk of dysplasia in the ileal pouch, but the anal transition zone should be monitored periodically. New endoscopic and molecular screening approaches may further refine our current surveillance guidelines and our understanding of the natural history of dysplasia.

Knowledge Gaps among Physicians Caring for Multiethnic Populations at Increased Gastric Cancer Risk

( Shailja C. Shah ),( Steven H. Itzkowitz ),( Lina Jandorf ) 대한간학회 2018 Gut and Liver Vol.12 No.1

Background/Aims: Although gastric cancer (GC) prevalence in the United States overall is low, there is significantly elevated risk in certain racial/ethnic groups. Providers caring for high-risk populations may not be fully aware of GC risk factors and may underestimate the potential for selective screening. Our aim was to identify knowledge gaps among healthcare providers with respect to GC. Methods: An Internet-based survey was distributed to primary care providers (PCPs) and gastroenterologists in New York City, which included questions regarding provider demographics, practice environment, GC risk factors, Helicobacter pylori, and screening practices. Three case vignettes were used to assess clinical management. Results: Of 151 included providers (111 PCPs, 40 gastroenterologists), most reported caring for a racially/ethnically diverse population and 58% recommended GC screening for select populations. Although >85% recommended against testing patients from regions where H. pylori, a known carcinogen, is endemic, <50% were able to correctly identify non-Asian endemic regions. Minorities of respondents correctly identified Hispanic/Latino (29%), Black (22%), and Eastern European/Russian (19.7%) as additional higher-risk races/ethnicities. Vignette-based questions highlighted variability in the management of potentially higher-risk patients. Conclusions: Despite caring for multiracial/ethnic populations, providers demonstrated deficiencies in identifying and managing patients with elevated GC risk. Focused educational efforts should be considered to address these deficiencies. (Gut Liver 2018;12:38-45)

Inflammatory Bowel Disease and Primary Sclerosing Cholangitis: A Review of the Phenotype and Associated Specific Features

( Carolina Palmela ),( Farhad Peerani ),( Daniel Castaneda ),( Joana Torres ),( Steven H. Itzkowitz ) 대한간학회 2018 Gut and Liver Vol.12 No.1

Primary sclerosing cholangitis (PSC) is a chronic, progressive cholestatic disease that is associated with inflammatory bowel disease (IBD) in approximately 70% of cases. Although the pathogenesis is still unknown for both diseases, there is increasing evidence to indicate that they share a common underlying predisposition. Herein, we review the epidemiology, diagnosis, disease pathogenesis, and specific clinical features of the PSC-IBD phenotype. Patients with PSC-IBD have a distinct IBD phenotype with an increased incidence of pancolitis, backwash ileitis, and rectal sparing. Despite often having extensive colonic involvement, these patients present with mild intestinal symptoms or are even asymptomatic, which can delay the diagnosis of IBD. Although the IBD phenotype has been well characterized in PSC patients, the natural history and disease behavior of PSC in PSC-IBD patients is less well defined. There is conflicting evidence regarding the course of IBD in PSC-IBD patients who receive liver transplantation and their risk of recurrent PSC. IBD may also be associated with an increased risk of cholangiocarcinoma in PSC patients. Overall, the PSC-IBD population has an increased risk of developing colorectal neoplasia compared to the conventional IBD population. Lifelong annual surveillance colonoscopy is currently recommended. (Gut Liver 2018;12:17-29)

Upper Endoscopy up to 3 Years Prior to a Diagnosis of Gastric Cancer Is Associated With Lower Stage of Disease in a USA Multiethnic Urban Population, a Retrospective Study

Shah, Shailja C.,Nakata, Chiaki,Polydorides, Alexandros D.,Peek, Richard M. Jr,Itzkowitz, Steven H. The Korean Society for Preventive Medicine 2019 Journal of Preventive Medicine and Public Health Vol.52 No.3

Objectives: In the USA, certain races and ethnicities have a disproportionately higher gastric cancer burden. Selective screening might allow for earlier detection and curative resection. Among a USA-based multiracial and ethnic cohort diagnosed with non-cardia gastric cancer (NCGC), we aimed to identify factors associated with curable stage disease at diagnosis. Methods: We retrospectively identified endoscopically diagnosed and histologically confirmed cases of NCGC at Mount Sinai Hospital in New York City. Demographic, clinical, endoscopic and histologic factors, as well as grade/stage of NCGC at diagnosis were documented. The primary outcome was the frequency of curable-stage NCGC (stage 0-1a) at diagnosis in patients with versus without an endoscopy negative for malignancy prior to their index exam diagnosing NCGC. Additional factors associated with curable-stage disease at diagnosis were determined. Results: A total of 103 racially and ethnically diverse patients were included. Nearly 38% of NCGC were stage 0-Ia, 34% stage Ib-III, and 20.3% stage IV at diagnosis. A significantly higher frequency of NCGC was diagnosed in curable stages among patients who had undergone an endoscopy that was negative for malignancy prior to their index endoscopy that diagnosed NCGC, compared to patients without a negative endoscopy prior to their index exam (69.6% vs. 28.6%, p=0.003). A prior negative endoscopy was associated with 94.0% higher likelihood of diagnosing curable-stage NCGC (p=0.003). No other factors analyzed were associated with curablestage NCGC at diagnosis. Conclusions: Endoscopic screening and surveillance in select high-risk populations might increase diagnoses of curable-stage NCGC. These findings warrant confirmation in larger, prospective studies.

Effect of Functional Status on the Quality of Bowel Preparation in Elderly Patients Undergoing Screening and Surveillance Colonoscopy

Akash Kumar,Lisa Lin,Oren Bernheim,Emilia Bagiella,Lina Jandorf,Steven H. Itzkowitz,Brijen J. Shah 거트앤리버 소화기연관학회협의회 2016 Gut and Liver Vol.10 No.4

Background/Aims: Optimal bowel preparation is essential for successful screening or for surveillance colonoscopy (SC). Inadequate bowel preparation is associated with older age, the male gender, and the presence of certain comorbidities. However, the association between patients’ functional status and bowel preparation quality has not been studied. We prospectively examined the relationship between functional status, namely, the ability to perform activities of daily living (ADLs) and ambulate, and the quality of bowel preparation in elderly patients undergoing SC. Methods: Before undergoing SC, 88 elderly patients were surveyed regarding their functional status, specifically regarding their ability to perform ADLs and ambulate a quarter of a mile. Gastroenterologists then determined the quality of the bowel preparation, which was classified as either adequate or inadequate. Then, the frequency of inadequate bowel preparation in patients who did or did not experience difficulty performing ADLs and ambulating was calculated. Results: Difficulty ambulating (unadjusted odds ratio [OR], 4.83; p<0.001), difficulty performing ADLs (OR, 2.93; p=0.001), and history of diabetes (OR, 2.88; p=0.007) were significant univariate predictors of inadequate bowel preparation. After adjusting for the above variables, only difficulty ambulating (adjusted OR, 5.78; p=0.004) was an independent predictor of inadequate bowel preparation. Conclusions: Difficulty with ambulation is a strong predictor of inadequate bowel preparation in elderly patients undergoing SC.

Screening Colonoscopy among Uninsured and Underinsured Urban Minorities

( Tyson H Collazo ),( Lina Jandorf ),( Linda Thelemaque ),( Kristen Lee ),( Steven H Itzkowitz ) 대한소화기학회 2015 Gut and Liver Vol.9 No.4

Background/Aims: Uninsured individuals have lower rates of screening colonoscopy (SC), and little is known regarding the pathology results obtained when they undergo colonoscopies. Since 2004, we have participated in a program that offers SC to uninsured New Yorkers; herein, we report our findings. Methods: Uninsured, average-risk patients who were at least 50 years of age underwent SC at our institution between April 2004 and June 2011. We analyzed polyp pathology, location, size, incidence of adenomas, and incidence of adenomas with advanced pathology (AAP) with respect to ethnicity, gender, and age. Results: Out of 493 referrals, 222 patients completed the colonoscopies. Polyps were identified in 21.2% of all patients; 14% had adenomas, and 4.5% had AAP. The rates of adenomas among African-Americans, Hispanics, and Whites were 24.3%, 12.1%, and 11.6%, respectively, and the corresponding rates of AAP were 10.8%, 3.5%, and 2.3%. Differences in the polyp type, location, and AAP did not reach statistical significance with respect to ethnicity or gender. Patients aged 60 and older were found to have a higher rate of advanced adenomas compared with younger patients (8.6% vs 2.6%, p=0.047). Conclusions: Further efforts to fund screening colonoscopies for uninsured individuals will likely result in the identification of advanced lesions of the colon before they progress to colorectal cancer. (Gut Liver 2015;9:502-508)

N-glycosylation status of β-haptoglobin in sera of patients with colon cancer, chronic inflammatory diseases and normal subjects

Park, Seung-Yeol,Yoon, Seon-Joo,Jeong, Yeon-Tae,Kim, Jin-Man,Kim, Ji-Yeon,Bernert, Bradford,Ullman, Thomas,Itzkowitz, Steven H.,Kim, Jung-Hoe,Hakomori, Sen-itiroh Wiley Subscription Services, Inc., A Wiley Company 2010 International journal of cancer: Journal internati Vol.126 No.1

<P>N-glycosylation status of purified β-haptoglobin from sera of 17 patients, and from sera of 14 healthy volunteer subjects, was compared by blotting with various lectins and antibodies. Patients in this study were diagnosed as having colon cancer through histological examination of each tumor tissue by biopsy. Blotting index of serum β-haptoglobin with Aleuria aurantia lectin (AAL) was clearly higher for cancer patients than for healthy subjects. No such distinction was observed for blotting with three other lectins and two monoclonal antibodies. To determine tumor-associated reactivity of AAL binding as compared to inflammatory processes in colonic tissues, β-haptoglobin separated from sera of 5 patients with Crohn's disease (CD), and 4 patients with ulcerative colitis (UC), was studied. All these cases, except one case of UC, showed AAL index lower than that in cancer cases, similarly to healthy subjects. The higher AAL binding of β-haptoglobin in colon cancer patients than in healthy subjects appeared to be due to α-L-fucosyl residue, since it was eliminated by bovine kidney α-fucosidase treatment. N-linked glycans of serum haptoglobin from colon cancer patients vs. healthy subjects were released by N-glycanase, fluorescence-labeled, and subjected to normal-phase high performance liquid chromatography (NP-HPLC). Glycan structures were determined based on glucose unit (GU) values and their changes upon sequential treatment with various exoglycosidases. Glycosyl sequences and their branching status of glycans from 14 cases of serum β-haptoglobin were characterized. The identified glycans were sialylated or nonsialylated, bi-antennary or tri-antennary structures, with or without terminal fucosylation.</P>

Upper Endoscopy up to 3 Years Prior to a Diagnosis of Gastric Cancer Is Associated With Lower Stage of Disease in a USA Multiethnic Urban Population, a Retrospective Study

Shailja C. Shah,Chiaki Nakata,Alexandros D. Polydorides,Richard M. Peek Jr,Steven H. Itzkowitz 대한예방의학회 2019 예방의학회지 Vol.52 No.3

Objectives: In the USA, certain races and ethnicities have a disproportionately higher gastric cancer burden. Selective screening might allow for earlier detection and curative resection. Among a USA-based multiracial and ethnic cohort diagnosed with non-cardia gastric cancer (NCGC), we aimed to identify factors associated with curable stage disease at diagnosis. Methods: We retrospectively identified endoscopically diagnosed and histologically confirmed cases of NCGC at Mount Sinai Hospital in New York City. Demographic, clinical, endoscopic and histologic factors, as well as grade/stage of NCGC at diagnosis were documented. The primary outcome was the frequency of curable-stage NCGC (stage 0-1a) at diagnosis in patients with versus without an endoscopy negative for malignancy prior to their index exam diagnosing NCGC. Additional factors associated with curable-stage disease at diagnosis were determined. Results: A total of 103 racially and ethnically diverse patients were included. Nearly 38% of NCGC were stage 0-Ia, 34% stage Ib-III, and 20.3% stage IV at diagnosis. A significantly higher frequency of NCGC was diagnosed in curable stages among patients who had undergone an endoscopy that was negative for malignancy prior to their index endoscopy that diagnosed NCGC, compared to patients without a negative endoscopy prior to their index exam (69.6% vs. 28.6%, p=0.003). A prior negative endoscopy was associated with 94.0% higher likelihood of diagnosing curable-stage NCGC (p=0.003). No other factors analyzed were associated with curable-stage NCGC at diagnosis. Conclusions: Endoscopic screening and surveillance in select high-risk populations might increase diagnoses of curable-stage NCGC. These findings warrant confirmation in larger, prospective studies.