Caroline Hwang

Pancreatic Cancer Screening in a Prospective Cohort of High-Risk Patients: A Comprehensive Strategy of Imaging and Genetics

Purpose: Pancreatic cancer is a virtually uniformly fatal disease. We aimed to determine if screening to identify curable neoplasms is effective when offered to patients at high risk. Experimental Design: Patients at high risk of pancreatic cancer were prospectively enrolled into a screening program. Endoscopic ultrasound (EUS), magnetic resonance imaging (MRI), and genetic testing were offered by a multidisciplinary team according to each patients risk. Results: Fifty-one patients in 43 families were enrolled, with mean age of 52 years, 35% of whom were male. Of these patients, 31 underwent EUS and 33 MRI. EUS revealed two patients with pancreatic cancer (one resectable, one metastatic), five with intraductal papillary mucinous neoplasms (IPMN), seven with cysts, and six with parenchymal changes. Five had pancreatic surgery (one total pancreatectomy for pancreatic cancer, three distal and one central pancreatectomy for pancreatic intraepithelial neoplasia 2 and IPMN). A total of 24 (47%) had genetic testing (19 for BRCA1/2 mutations, 4 for CDKN2A, 1 for MLH1/MSH2) and 7 were positive for BRCA1/2 mutations. Four extrapancreatic neoplasms were found: two ovarian cancers on prophylactic total abdominal hysterectomy and bilateral salpingo-oophorectomy, one carcinoid, and one papillary thyroid carcinoma. Overall, 6 (12%) of the 51 patients had neoplastic lesions in the pancreas and 9 (18%) had neoplasms in any location. All were on the initial round of screening. All patients remain alive and without complications of screening. Conclusions: Pancreatic cancer screening for high-risk patients with a comprehensive strategy of imaging and genetics is effective and identifies curable neoplasms that can be resected. Ongoing study will better define who will benefit from screening and what screening strategy will be the most effective. Clin Cancer Res; 16(20); 5028–37. ©2010 AACR.

Micronutrient deficiencies in inflammatory bowel disease: from A to zinc.

Inflammatory bowel disease (IBD) has classically been associated with malnutrition and weight loss, although this has become less common with advances in treatment and greater proportions of patients attaining clinical remission. However, micronutrient deficiencies are still relatively common, particularly in CD patients with active small bowel disease and/or multiple resections. This is an updated literature review of the prevalence of major micronutrient deficiencies in IBD patients, focusing on those associated with important extraintestinal complications, including anemia (iron, folate, vitamin B12) bone disease (calcium, vitamin D, and possibly vitamin K), hypercoagulability (folate, vitamins B6, and B12), wound healing (zinc, vitamins A and C), and colorectal cancer risk (folate and possibly vitamin D and calcium). (Inflamm Bowel Dis 2012)

High Prevalence of BRCA1 and BRCA2 Germline Mutations With Loss of Heterozygosity In a Series of Resected Pancreatic Adenocarcinoma and Other Neoplastic Lesions

PURPOSE Pancreatic ductal adenocarcinoma (PDAC) is associated with the breast ovarian cancer syndrome (BRCA1/BRCA2) mutations. It is unknown if this association is causal. EXPERIMENTAL DESIGN This is a single-site study of patients who underwent surgical pancreatic tumor resection and self-identified as Ashkenazi Jewish. DNA from normal pancreatic tissue was genotyped for the three Ashkenazi Jewish BRCA1/2 founder mutations BRCA1 185delAG, BRCA1 5382insC, and BRCA2 6174delT, and loss of heterozygosity (LOH) was determined by sequencing DNA from microdissected tumor. When additional tumor tissue was available, p53 immunohistochemistry (IHC) was conducted. RESULTS Thirty-seven patients underwent surgery for PDAC, seven for intraductal papillary mucinous neoplasm (IPMN), and 19 for other diseases. A high prevalence of BRCA1/2 mutations was found in the surgical cohort (12/63; 19.0%; P < 0.001), PDAC cohort (8/37; 21.6%; P < 0.001), and IPMN cohort (2/7; 28.6%; P = .01) compared with published control mutation frequency. A high prevalence of BRCA1 185delAG (8.1%; P < 0.001) and BRCA2 6174delT (10.8%; P < 0.001) in Ashkenazi Jewish patients with PDAC was shown. BRCA1/2 LOH was found in 2 of 4 BRCA1-associated PDACs and 3 of 4 BRCA2-associated PDACs. Positive p53 IHC was found in 5 of 8 BRCA1/2 PDACs. CONCLUSIONS We show a high prevalence of BRCA1/2 mutations with LOH in an Ashkenazi Jewish cohort of surgically resected PDAC and neoplastic lesions, suggesting that these germline mutations are causal in selected individuals.

Popular exclusionary diets for inflammatory bowel disease: the search for a dietary culprit.

Abstract:The evolving understanding of the role of the microbiome and environmental factors in the pathogenesis of inflammatory bowel disease makes diet an interesting and potentially powerful tool in the treatment of disease. However, at this time, evidence is limited but anecdotal reports of success abound. There is a bewildering array of new diets being tried by patients in an attempt to control diseases. This review attempts to summarize the most common diets for the treating physician.

BRCA1 and BRCA2 germline mutations are frequently demonstrated in both high‐risk pancreatic cancer screening and pancreatic cancer cohorts

Approximately 10% of pancreatic ductal adenocarcinoma (PDAC) is due to a genetic predisposition, including the breast and ovarian cancer syndrome germline mutations BRCA1 and BRCA2. Knowledge of specific genetic mutations predisposing to PDAC may enable risk stratification, early detection, and the development of effective screening and surveillance programs. In the current study, the authors attempted to determine the diagnostic yield of testing for BRCA1/2 germline mutations in a PDAC screening cohort and a PDAC cohort referred for genetic testing.

Absence of pancreatic intraepithelial neoplasia predicts poor survival after resection of pancreatic cancer.

Objectives Pancreatic intraepithelial neoplasia (PanIN), thought to represent the dominant precursor of pancreatic adenocarcinoma (PDAC), is often found synchronously adjacent to resected PDAC tumors. However, its prognostic significance on outcome after PDAC resection is unknown. Methods A total of 342 patients who underwent resection for PDAC between 2005 and 2010 at a single institution were identified and stratified according to highest grade of PanIN demonstrated surrounding the tumor. Clinical and pathologic characteristics of each patient and tissue were recorded and analyzed. The primary outcome was length of survival after resection. Results An absence of PanIN lesions was identified in 32 patients (9%), low grade PanIN without synchronous high grade lesions was identified in 52 patients (15%), and high grade PanIN was found in 258 patients (75%). Median survival were 12.8 months for the non-PanIN group, 26.3 months for the low-grade PanIN group, and 23.8 months for the high-grade PanIN groups (P = 0.043). In multivariable analysis, absence of PanIN was independently associated with poor survival (P = 0.002). Conclusions The patients who demonstrate an absence of PanIN in the pancreatic tissue adjacent to the resected PDAC tumor have shorter postresection survival compared with those who demonstrate a PanIN lesion.

Knowledge, Attitudes, and Beliefs Regarding the Role of Nutrition in IBD Among Patients and Providers.

Background:Malnutrition is common in inflammatory bowel disease (IBD). Identifying patients who are malnourished or at risk for malnutrition may lead to early intervention and improve patient outcomes. To date, little is known about the role of nutritional assessment and management in IBD care. We aimed to evaluate knowledge, attitudes, and beliefs regarding nutrition in IBD among patients and providers. Methods:Surveys were mailed electronically to patients and providers identified through their membership in the Crohns & Colitis Foundation of America. In addition, patient and provider focus groups were conducted to explore nutrition-related themes. These surveys and focus groups were designed to evaluate knowledge and perceived importance of nutrition, patient–provider interactions regarding nutrition and use of nutritional resources. Results:There were 223 provider respondents (65.5% gastroenterologists, 15.2% nurses, and 6.7% dietitians). Forty-one percent of the gastroenterologists rated their knowledge of nutrition in IBD as “very good” compared with 87% of dietitians and 16% of nurses (P < 0.001). Thirty-three percent of the gastroenterologists reported not routinely screening their IBD patients for malnutrition. The patient survey had 567 respondents with 27% rating their knowledge of nutrition in IBD as “very good.” In the focus groups, a lack of adequate IBD nutritional resources was evident along with a desire for improved access to nutrition specialists. Conclusions:Significant gaps in knowledge relating to nutrition in IBD seem to exist. Targeted educational initiatives and improved access to nutritional experts are warranted. In addition, a standardized process for the assessment of malnutrition among patients with IBD should be developed.

On the Question of Ethnicity and Its Impact on IBD-Related Outcomes

The global incidence of inflammatory bowel disease (IBD) has risen steadily over the last half century [1]. Previously considered a disease which predominantly afflicted Caucasians in industrialized countries, IBD is being increasingly reported in developing countries as they become ‘‘Westernized,’’ supporting the importance of environmental factors in disease pathogenesis [1, 2]. Moreover, rates of IBD among immigrant and minority populations in Canada and several western European countries are rising [2, 3]. Though population-based studies in the United States are lacking, one recent study utilizing the National Inpatient Sample (a large nationally-representative database of hospital admissions), demonstrated a temporal increase in non-white minority patients hospitalized for IBD over the last decades [4]. Within the United States, Hispanics are amongst the largest and fastest-growing minority groups, currently accounting for 16 % of the US population. Data regarding ethnic variations of disease epidemiology and phenotype amongst Hispanic IBD patients have been limited, with available literature inconsistent. For instance, there is conflicting data on whether Hispanics have higher or lower rates of Crohn’s disease [5–7], perianal complications [6, 8], and extraintestinal manifestations [5–7], when compared to Caucasians. This variability of findings is probably due to the genetic heterogeneity of Hispanics in the United States, which can include European (Spanish and Portuguese), Caribbean, and Native-American ancestry. Caribbean Hispanics are often categorized as Black (African descent) or White (European) races. With regard to treatment and outcome disparities amongst Hispanics, the current literature highlights the difficulty of separating ethnic-based differences in disease course with issues of access to care. Several retrospective studies of underserved cohorts in safety-net hospitals have suggested a smaller proportion of Hispanic IBD patients, compared to Caucasians, are prescribed immunomodulator and biologic therapy for their disease [5, 7]. Moreover, Hispanics appear to be less likely to undergo surgery for UC and Crohn’s, based on two studies utilizing the National Inpatient Sample [8, 9]. Nevertheless, patients with Medicaid were also less likely to undergo surgery than patients with private insurance, suggesting a potential contribution from socioeconomic factors. Given these apparent treatment disparities, one might suspect that Hispanic IBD patients would have poorer outcomes. In particular, surgical outcomes would be expected to underscore ethnic disparities amongst the sickest IBD patients, given surgery is reserved for medically-refractory disease or disease complications (strictures, fistulas, neoplasia). In this month’s Digestive Diseases and Sciences, Dr. Yarur and colleagues report on their findings of surgical outcomes amongst Hispanics compared to non-Hispanics [10]. To date, this is the first study evaluating ethnic differences in perioperative complication rates of IBD-related surgery. Importantly, the authors sought to control for access to care issues by comparing Hispanic and non-Hispanic patients within a single safety-net health care system (Miami-Dade County) and including only patients who received regular gastroenterological care for at least 6 months prior to their surgery. Socioeconomic differences were thought less likely, C. Hwang Division of Gastrointestinal and Liver Diseases, University of Southern California, Los Angeles, CA, USA

Su1817 EUS Features of Chronic Pancreatitis Do Not Correlate With Pathologic Findings of Abnormal Parenchyma in High-Risk Pancreas Cancer Patients Undergoing Pancreatic Resection

Background: The success of pancreatic cancer (PC) surveillance depends to a large extent on the commitment of participants to adhere to the repeated follow-up investigations. Though the results of our recently conducted retrospective study showed that the burden of PC surveillance is acceptable, a prospective assessment was warranted to document the mental and psychological impact of PC screening. We aimed to investigate possible changes in cancer worries and levels of anxiety and depression in high-risk individuals participating in a PC surveillance program. Methods Eligible for this prospective questionnaire study were high-risk individuals participating in our multicenter nationwide endoscopic ultrasound (EUS)-MRI-based PC-surveillance study. High-risk individuals were those with a strong family history of PC or carriers of PC-prone gene mutations. Questionnaires, administered both before (pretest) and after (posttest) the baseline PC screening investigations, assessed concerns about developing cancer (CancerWorry Scale), and levels of anxiety and depression (Hospital Anxiety and Depression scale). Results Of the 54 high-risk individuals, 47 (87%) completed both the pretest and posttest questionnaires (38% male, mean age= 52 yr., range 20-74 yrs.). Of these, 44 participated in the PC screening and 3 declined. All participants underwent both EUS and MRI. Prior to undergoing PC screening, 36% of the participants reported being fearful about undergoing EUS, whereas 5% was fearful about the MRI. After screening, 2.3% of all participants feared the next EUS (p<.001) and 2.3% the next MRI. The mean level of depression was significantly higher prior to screening as compared to after screening (p<.001). However, the number of participants with clinical levels of anxiety and/ or depression was low (n=5) and remained stable over time. Prior to, as well as after screening the most frequently reported worries were about the possibility of developing cancer themselves (29% at both time points) and the chance that relatives would develop cancer (19% and 21%, respectively). The 3 individuals who did not undergo screening indicated that they were not very fearful of the MRI or EUS. They also had low levels of anxiety, depression and cancer worries. Conclusion: The results of this prospective study indicate that: (1) the expected burden of EUS is higher than the actual experienced burden; and that (2) mean levels of anxiety, depression and cancer worries are not significantly influenced by participating in the PC screening program. This finding is of great importance for this group that is at high risk of developing pancreatic cancer and might benefit from participation in a life-long repeated PC surveillance program.