Bhavana Bhagya Rao

Hepatic hyperplasia and cancer in rats: Metabolic alterations associated with cell growth

BACKGROUND & AIMS We showed previously that the peroxisome proliferators di(2-ethylhexyl)phthalate (DEHP), clofibrate, and 4-chloro-6-(2,3 xylidino)-2-pyrimidinylthio (N-beta-hydroxyl)acetamide (BR931) alter hepatic sex steroid metabolism and receptor expression during induction of hepatic hyperplasia and hepatocellular carcinoma (HCC) in rats. The aim of this study was to identify metabolic changes associated with cell growth during hyperplasia and HCC. METHODS Hepatic hyperplasia was induced in male rats by a diet containing DEHP and clofibrate for 3-60 days. HCC was induced by feeding a diet containing BR931, a more potent hepatocarcinogen, for 10 months. RESULTS Cholesterol biosynthesis was depressed in hyperplastic livers but increased in HCC. Glucose-6-phosphate dehydrogenase (G6PD) activity was inhibited in hyperplastic liver as well as in HCC, whereas malic enzyme activity increased severalfold. Protein and messenger RNA (mRNA) levels for both G6PD and malic enzyme increased in hyperplastic livers and HCC. mRNA levels for 3-hydroxy-3-methylglutaryl-coenzyme A reductase decreased in hyperplasia and increased in HCC, whereas low-density lipoprotein receptor mRNA increased in hyperplasia and decreased in HCC. CONCLUSIONS Neoplastic cells acquire a growth advantage by their capacity to synthesize cholesterol and obtain reduced nicotinamide adenine dinucleotide phosphate by the malic enzyme pathway when G6PD activity is inhibited by peroxisome proliferators.

Renal outcomes of bariatric surgery in obese adults with diabetic kidney disease

Obesity is a pandemic with several significant adverse health outcomes. Chronic kidney disease has been an overlooked consequence of obesity. Among diabetics, obesity is known to amplify the risk for kidney disease. Although bariatric surgery promises significant and sustained weight reduction with favorable impact on metabolic parameters such as glycemic control, hypertension and dyslipidemia, its impact on the renal complications of diabetes is poorly understood. This paper aims to comprehensively evaluate the evidence in the published literature on the impact of bariatric surgery on renal outcomes in obese adults with diabetic kidney disease. While many observational studies have demonstrated significant reduction in proteinuria after bariatric surgery, there is paucity of data regarding changes in renal filtration function such as doubling of serum creatinine or progression to end stage kidney disease. No randomized controlled trials comparing medical vs. surgical therapy in obese adults with diabetic kidney disease exist, hence assessing the metabolic benefits vs. the surgical risks is important before recommending bariatric surgery to this growing patient population. Future studies require a collaborative effort between bariatric surgeons and nephrologists to measure long-term effects of bariatric surgery on renal outcomes incorporating evolving markers of kidney injury to advance this field.

Silent Crohn's Disease Predicts Increased Bowel Damage During Multiyear Follow-up: The Consequences of Under-reporting Active Inflammation

Background:Patients with Crohns disease (CD) in clinical remission with elevated C-reactive protein (CRP) have been labeled “silent CD” and have increased 2-year hospitalization rates when compared with asymptomatic patients with no biochemical evidence of inflammation. The risk of cumulative bowel damage in patients with silent CD is unknown. Methods:Observational study of patients with CD prospectively followed in a tertiary referral natural history registry. Consecutive patients with CD in clinical remission (Harvey–Bradshaw Index ⩽ 4) with good quality of life (short inflammatory bowel disease questionnaire score ≥ 50), and same day CRP measurement at first encounter, followed for a minimum of 4 years formed the study population. Disease trajectory was determined using change in Lémann Index as a measure of bowel damage. Results:A total of 185 patients with CD (median age 42 years; 51.4% men) were included in the study. CRP elevation was observed in 43 (23%) patients (Silent CD cohort). Majority of them showed worsening disease trajectories based on change in Lémann Index when compared with asymptomatic patients with normal CRP (65% versus 36%, P < 0.0001). Multinomial logistic regression analysis demonstrated that elevated CRP was independently associated with 7-fold higher odds (odds ratio = 6.93, P < 0.0001) of having worse disease trajectories when compared with stable disease trajectories. Conclusions:Two-thirds of patients with CD in clinical remission, while demonstrating elevated CRP, will develop bowel damage over the ensuing years, despite feeling well. These patients with silent CD are an “at-risk” group who warrant further investigation to prevent development of disease-related complications.

The Cost of Crohnʼs Disease: Varied Health Care Expenditure Patterns Across Distinct Disease Trajectories

Background: Patients with Crohns disease (CD) encompass a heterogeneous disease spectrum, with variable health care utilization and expenditure patterns. Lémann Index (LI) is a metric that quantifies cumulative bowel damage and has shown utility in delineating distinct disease phenotypes. We aimed to characterize the financial burden from all medical care in CD cohort in relation to the variations in LI-based disease phenotypes. Methods: CD patients with 5-year (y) follow-up from a prospective registry were included. LI was calculated from first (LI1) and last (LI2) clinical encounters. Change in score (LI2-LI1) or Delta LI (DLI) was used for association analysis with health care expenditures. Results: A total of 243 patients with CD formed the study population (median age, 44 years; 58% women; median disease duration 12 years). DLI was used to define disease trajectories: DLI <0 (indicating improving bowel damage); DLI = 0 (stable); DLI >0 (worsening); which comprised 15.6%, 30.9%, and 53.5% of the cohort, respectively. Patients with DLI >0 had significantly higher CD-related surgeries, health care utilization, medication (steroids and biologics) use as well as higher median 5 years total and stratified charges compared with the other groups. Total 5-year expenditure was

Correlation of anemia status with worsening bowel damage as measured by Lémann Index in patients with Crohn's disease

56 million; 67% of which was related to hospitalization. Total expense showed independent positive correlation with LI2 (P = 0.001) and DLI (P = 0.001), and negative correlation with age (P = 0.029) and 5-year quality of life score (P = 0.024). Conclusions: The financial burden of CD is significantly associated with worsening bowel damage. Further research should focus on the prediction and management of the costliest/sickest patients with CD.

Endoscopic sonography and sonographically guided fine-needle aspiration biopsy in the diagnosis of unusual pancreatic metastases from synovial sarcoma

BACKGROUND There is evidence that anemia in Crohns disease (CD) is a predictor of disease severity. AIM To evaluate if patterns of anemia over time showed correlation with aggressive disease trajectory, as characterized by change in Lémann Index (LI), which is a metric that quantifies bowel damage. METHODS CD patients with 5 year (y) follow-up from a prospective registry were included. LI was calculated from the first (LI1) and last (LI2) clinical encounters. The change in score (LI2-LI1) or the Delta LI (DLI) was recorded. Patterns of anemia, healthcare utilization and disease activity scores were analyzed. RESULTS A total of 389 CD patients with 5y follow-up formed the study population [median age 40y (IQR: 31-53); 57.3% female; median disease duration 12y (IQR: 6-20.5), overall surgical exposure 69%]. Patients with anemia had significantly higher LI1, LI2, DLI and also significantly higher healthcare utilization and indices of disease activity, than patients without anemia (p<0.001). CD patients with anemia for any duration during the study had OR of 2.15 (95% CI 1.29-3.57, p=0.003) for worsening bowel damage over the 5y. CONCLUSION Based on a longitudinal analysis of CD patients, anemia status over time shows significant correlation with increasing Lémann index and aggressive disease trajectory.

Intraoperative enteroscopy in Peutz–Jeghers syndrome

Pancreatic metastases are commonly solitary solid lesions frequently derived from primary renal cell carcinoma, lung cancer, or melanoma. Very few case reports have described cystic‐appearing metastases in the pancreas and even fewer have reported a combination of cystic and solid metastatic lesions. Synovial sarcoma is a rare and aggressive soft tissue neoplasm, frequently metastasizing to the lungs and bones. We present a case of primary synovial sarcoma with multiple solid and cystic‐appearing pancreatic metastases diagnosed by endoscopic ultrasound and sonographically guided fine‐needle aspiration.

Outpatient Telephonic Transitional Care After Hospital Discharge Improves Survival in Cirrhotic Patients

1Department of Gastroenterology and Hepatology, Cleveland Clinic, Cleveland, USA. 2Department of Colorectal Surgery, Cleveland Clinic, Cleveland, USA. Correspondence: C.A.B. (email: burkec1@ccf.org) Published online 1 March 2018 Fig. 1 A 39-year-old Asian female presented for evaluation of recurrent small bowel obstruction (SBO) in the preceding year. She was recently diagnosed with Peutz–Jeghers syndrome, with genetic testing showing deletion of exons 2–8 in STK11 gene. Past history was notable for an abdominal surgery at 2 years of age, with unknown details. Endoscopic evaluation in preceding 6 months was notable for multiple hamartomatous polyps, 0.5–4 cm in size, throughout the stomach, small bowel and colon. Computerized tomographic enterography revealed multiple dilated small bowel loops with scattered foci of intussusception, suspected to be due to hamartomatous polyps, leading to recurrent SBO. Exploratory laparotomy with surgically assisted enteroscopy to terminal ileum and removal of all clinically significant polyps, i.e., “clean sweep”, was planned. Intraoperative findings included extensive intra-abdominal adhesions and prior SB resection with anastomotic stricture 60 cm proximal to the ileocecal valve. Surgical adhesiolysis and small bowel resection was performed along with endoscopic removal of over 30 polyps >10 cm in size and over 35 polyps 2–10 cm in size. These unique images depict the endoscopic appearance of transilluminated jejunum and ileum (Fig 1a), containing large polyps (Fig 1b), which were resected with hot snares and retrieved using roth net (Fig 1c) or via enterotomy. (Informed consent was obtained from the patient to publish these images.)

Epithelioid Granulomas Associate with Increased Severity and Progression of Crohn’s Disease, Based on 6-year Follow Up

BACKGROUND Intervention to improve outcomes in cirrhotic patients (CP) after hospital discharge often focus on 30 d readmission rate (RR). However, recent studies suggest dissociation between RR and survival. At our center, CP are now offered outpatient telephonic transitional care (OTTC) by a care coordinator for 30 d after hospital discharge. AIM To determine the effect of OTTC on survival in CP. METHODS In this cohort study from a tertiary center, CP who received OTTC formed the intervention group. They were compared with a control group discharged during the same period. Mortality and RR were compared between the groups. RESULTS After OTTC introduction, 194 CP were discharged. After applying exclusion criteria, 169 CP (51% male, mean age 58 years ± 12 years) were included. OTTC group comprised 76 patients and was compared with 93 controls. Baseline disease and index admission related characteristics were not significantly different between the groups. The intervention group showed significantly higher 6 mo survival compared to controls (84.2% vs 68.8%; P = 0.03), while RR at 1, 3, and 6 mo were comparable. On multivariable analysis, the intervention group showed lower odds for mortality compared to the controls (hazard ratio: 0.4; 95% confidence interval: 0.2-0.82; P = 0.012), while higher model for endstage liver disease scores were associated with higher mortality (hazard ratio: 1.05; 95% confidence interval: 1.01-1.1; P = 0.024).

Intratumoral endoscopy and diagnosis of a large gastrointestinal stromal tumor.

BACKGROUND & AIMS: Epithelioid granulomas are characteristics of a subset of patients with Crohn’s disease (CD), but their significance, with regard to disease progression and severity, is unclear. We investigated the relationship between granulomas and CD severity over a 6‐year time period in a large cohort of patients. METHODS: We performed a retrospective study of patients with CD seen at the Inflammatory Bowel Disease Center at the University of Pittsburgh; data were collected from 2009 through 2014 and patients were assigned to groups with and without histologic evidence of granuloma. Demographic, clinical (including disease activity, quality of life, medication use, and healthcare utilization), and laboratory data were used in association and survival analyses. Differences between groups were evaluated using the Mann‐Whitney U‐test for continuous variables. RESULTS: Of 1466 patients with CD, granulomas were identified in 187 (12.8%). In the subset of patients who underwent surgery, 21.0% had granulomas. The presence of granuloma was associated with increased serum levels of c‐reactive protein (odds ratio [OR], 2.9; 95% CI, 2.078–4.208; P < .0001), younger mean age at diagnosis (23.6 ± 11.3 years in patients with granulomas vs 27.9 ± 13.3 years in patients without; P = .0005), higher rates of stricturing or penetrating disease phenotype, higher rates of steroid and narcotic use, and higher healthcare utilization. Among patients that underwent surgery, the presence of granulomas was associated with need for repeat surgery during the 6‐year observation period (OR, 2.5; 95% CI, 1.54–4.02; P = .0002). Infliximab use was associated with detection of granuloma in a significantly lower proportion of surgical specimens compared to patients who had not been treated with a biologic agent (OR, 0.22; 95 CI, 0.05–0.97; P = .03). CONCLUSIONS: Epithelioid granulomas develop in less than 13% of patients with CD, and are associated with a more aggressive disease phenotype. Patients who have undergone surgery for CD and have granulomas are at increased risk for repeat surgery within 6 years.