Thiruvengadam Muniraj

Pancreatic cancer: a comprehensive review and update.

The term pancreatic cancer encompasses both exocrine and endocrine tumors of the pancreas. More than 90% of pancreatic tumors originate from ductal epithelium and this reviewwill focus only on pancreatic ductal adenocarcinoma, which is commonly referred to as pancreatic cancer. The aim of this review is to update the primary practitioner on the epidemiology, genetics, risk factors, potential for screening, etiology, clinical presentation, diagnosis, and current medical and surgical management of pancreatic cancer.

Chronic pancreatitis, a comprehensive review and update. Part I: epidemiology, etiology, risk factors, genetics, pathophysiology, and clinical features.

Chronic pancreatitis is an irreversible condition of the pancreas characterized by chronic progressive pancreatic inflammation, fibrosis, and scarring resulting in loss of both exocrine (acinar) and endocrine (islet cells) tissue. As the definition implies, it is the inflammation-led fibrosis that culminates in CP. There are several conditions with exocrine insufficiency which need to be distinguished from CP such as post-surgical changes and Shwachman–Diamond Syndrome (the second most common cause for exocrine pancreatic insufficiency in children after cystic fibrosis). The anatomy of the pancreas was first described in the 17th century when the pancreatic duct was discovered (J.C. Wirsung, 1642) and the duodenal papilla was described (J.K. Brunner, 1683; C.B. Holdefreund, 1713; and A. Vater, 1750). The presence of fatty necrosis in acute pancreatitis was first shown by W. Balser (1882), and the autodigestive genesis was suspected by H. Chiari (1896). In 1788, Sir Thomas Cawley of England was the first one to describe on a “free living young man” who had died of diabetes, and on autopsy it was found that the pancreas was filled with multiple calculi. This is the first connection established between diabetes and pancreatitis. Paul Langerhans, who was born in Berlin in to a family of renowned physicians, is well known for pancreatic islets, and dendritic cells of the skin. In 1869, he worked on his PhD thesis on “Abdominal salivary gland” which is now known as the pancreas. During these studies he identified the “small homogeneous islands of clear cells lying throughout the gland.” After his death at the early age of 41 years (from tuberculosis), subsequent researchers magnanimously named these cells as “The islets of Langerhans” (Fig. 1). It was only in 1946 that Comfort et al. described the disease as chronic pancreatitis. Through conferences in Marseille, Cambridge, and Atlanta, the classification of acute and chronic pancreatitis has been revised several times. It has been more than two centuries since

Cold Snare Polypectomy for Large Sessile Colonic Polyps: A Single-Center Experience

Colonoscopic polypectomy has been shown to reduce the risk of colorectal cancer and the mortality. Postpolypectomy bleeding was reported to be lower with cold snare polypectomy (CSP) when compared with conventional polypectomy. CSP has traditionally been utilized only in smaller polyps below 1 cm. We retrospectively analyzed the CSP outcomes in patients with sessile polyps ≥10 mm in size and observed that CSP was feasible in large sessile polyps with no adverse events and with an acceptable rate of residual polyp on follow-up colonoscopy. Further prospective study in larger patient groups is warranted to determine optimal CSP techniques and whether CSP for large polyps has favorable efficacy in regard to complete polypectomy, procedure time, and complication rates relative to polypectomy with cautery.

Quality of Life in Chronic Pancreatitis is Determined by Constant Pain, Disability/Unemployment, Current Smoking, and Associated Co-Morbidities

Objectives:Chronic pancreatitis (CP) has a profound independent effect on quality of life (QOL). Our aim was to identify factors that impact the QOL in CP patients.Methods:We used data on 1,024 CP patients enrolled in the three NAPS2 studies. Information on demographics, risk factors, co-morbidities, disease phenotype, and treatments was obtained from responses to structured questionnaires. Physical and mental component summary (PCS and MCS, respectively) scores generated using responses to the Short Form-12 (SF-12) survey were used to assess QOL at enrollment. Multivariable linear regression models determined independent predictors of QOL.Results:Mean PCS and MCS scores were 36.7±11.7 and 42.4±12.2, respectively. Significant (P<0.05) negative impact on PCS scores in multivariable analyses was noted owing to constant mild–moderate pain with episodes of severe pain or constant severe pain (10 points), constant mild–moderate pain (5.2), pain-related disability/unemployment (5.1), current smoking (2.9 points), and medical co-morbidities. Significant (P<0.05) negative impact on MCS scores was related to constant pain irrespective of severity (6.8–6.9 points), current smoking (3.9 points), and pain-related disability/unemployment (2.4 points). In women, disability/unemployment resulted in an additional 3.7 point reduction in MCS score. Final multivariable models explained 27% and 18% of the variance in PCS and MCS scores, respectively. Etiology, disease duration, pancreatic morphology, diabetes, exocrine insufficiency, and prior endotherapy/pancreatic surgery had no significant independent effect on QOL.Conclusions:Constant pain, pain-related disability/unemployment, current smoking, and concurrent co-morbidities significantly affect the QOL in CP. Further research is needed to identify factors impacting QOL not explained by our analyses.

Laparoscopic Staging and Surgical Treatment of Pancreatic Cancer

Pancreatic cancer is the tenth most common cancer and the fourth leading cause of cancer deaths in the United States. Surgery remains a cornerstone in the treatment of pancreatic cancer. Unfortunately, the percentage of patients presenting at the resectable stage is minimal. Although computed tomography (CT) scan remains the best modality to stage the tumor for resectability, laparoscopy and laparoscopic ultrasound offers its own advantages. Extended lymphadenectomy, portal vein resection, and arterial reconstruction have also been explored in multiple studies to enhance staging. The traditional pancreaticoduodenectomy (Whipples procedure) with regional lymphadenectomy is still the standard of care in the surgical treatment of pancreatic cancer.

Chronic pancreatitis, a comprehensive review and update. Part II: Diagnosis, complications, and management

Advances in research regarding chronic pancreatitis (CP) have improved our understanding of this disease. Despite this progress, the management of CP still remains less than optimal, with many patients who are symptomatic and have poor quality of life. Optimal management begins with an accurate diagnosis, identifying the cause, assessing the reversibility of the cause, and then the evaluation followed by treatment of symptoms and complications. This review focuses on areas with updated recent evidence.

Pancreatic neuroendocrine tumors

Pancreatic neuroendocrine tumors (PNETs) have an incidence of approximately 1 per 100,000 individuals per year, and account for 1–2% of all pancreatic tumors. The annual incidence in the United States is about 3.65 per 100,000 population. Although they may manifest at any age, they most often occur in the fourth to sixth decades of life. Most PNETs are sporadic, but they can be associated with hereditary endocrinopathies involving loss of a possible tumor-suppressor gene, including Multiple Endocrine Neoplasia Type 1 (MEN1), Von Hippel Lindau (VHL) syndrome, Neurofibromatosis Type I (NF1), and Tuberous sclerosis. Approximately 80–100% of the patients with MEN1, up to 20% of the patients with VHL, 10% of the patients with NF1, and 1% of the patients with tuberous sclerosis will develop a PNET. Of these, MEN1 is the most common. It is characterized by pancreatic, pituitary, and parathyroid malignancies. MEN syndrome is present in 20–30% of patients with Zollinger–Ellison Syndrome (ZES), in whom gastrinomas tend to be multifocal, less aggressive, and located submucosally in the duodenum.

Racial Differences in the Clinical Profile, Causes, and Outcome of Chronic Pancreatitis.

OBJECTIVES:Racial differences in susceptibility and progression of pancreatitis have been reported in epidemiologic studies using administrative or retrospective data. There has been little study, however, on the clinical profile, causes, and outcome of chronic pancreatitis (CP) in black patients.METHODS:We analyzed data on black patients with CP prospectively enrolled in the multicenter North American Pancreatitis Studies from 26 US centers during the years 2000–2014. CP was defined by definitive evidence on imaging studies or histology. Information on demographics, etiology, risk factors, disease phenotype, treatment, and perceived effectiveness was obtained from responses to detailed questionnaires completed by both patients and physicians.RESULTS:Of the 1,159 patients enrolled, 248 (21%) were black. When compared with whites, blacks were significantly more likely to be male (60.9 vs. 53%), ever (88.2 vs. 71.8%), or current smokers (64.2 vs. 45.9%), or have a physician-defined alcohol etiology (77 vs. 41.9%). There was no overall difference in the duration of CP although for alcoholic CP, blacks had a longer duration of disease (8.6 vs. 6.97 years; P=0.02). Blacks were also significantly more likely to have advanced changes on pancreatic morphology (calcifications (63.3 vs. 55.2%), atrophy (43.2 vs. 34.6%), pancreatic ductal stricture or dilatation (72.6 vs. 65.5%) or common bile duct stricture (18.6 vs. 8.2%)) and function (endocrine insufficiency 39.9 vs. 30.2%). Moreover, the prevalence of any (94.7 vs. 83%), constant (62.6 vs. 51%), and severe (78.4 vs. 65.8%) pain and disability (35.1 vs. 21.4%) were significantly higher in blacks. Observed differences were in part related to variances in etiology and duration of disease. No differences in medical or endoscopic treatments were seen between races although prior cholecystectomy (31.1 vs. 19%) was more common in white patients.CONCLUSIONS:Differences were observed between blacks and whites in the underlying cause, morphologic expression, and pain characteristics of CP, which in part are explained by the underlying risk factor(s) with alcohol and tobacco being much more frequent in black patients as well as disease duration.

A double-blind, randomized, sham-controlled trial of the effect of a radiation-attenuating drape on radiation exposure to endoscopy staff during ERCP.

OBJECTIVES:Endoscopic retrograde cholangiopancreatography (ERCP) is associated with radiation exposure to the endoscopist and staff that may be significant in high-volume centers. We investigated whether a radiation-attenuating drape over the fluoroscopy image intensifier reduces radiation exposure during ERCP.METHODS:We performed a prospective, randomized, double-blind trial of 100 therapeutic ERCPs at a tertiary-care university center. Procedures were randomly assigned to groups receiving lead-free radiation-attenuating drapes (n=50) or identical sham drapes (n=50). The drapes were suspended around the fluoroscopy image intensifier during ERCP. The primary end point was the effective dose of radiation measured at the endoscopist’s eye and neck, and at the assisting nurse’s neck. The cumulative annual radiation exposure was also estimated.RESULTS:Fluoroscopy time, absorbed radiation dose, and dose area product were similar in the study groups. Mean effective dose for sham vs. radiation-attenuating drape was 0.21±0.27 vs. 0.02±0.02 mSv at the endoscopist’s eye, 0.35±0.44 vs. 0.03±0.03 mSv at the endoscopist’s neck, and 0.27±0.34 vs. 0.02±0.02 mSv at the nurse’s neck (P<0.0001 for all comparisons). The relative risk reduction in radiation was 90%, 91%, and 93% at the three sites. At a high-volume center in which an endoscopist performs 500 therapeutic ERCPs per year, the estimated cumulative annual effective dose at the endoscopist’s eye level is 126 mSv with conventional protection and 12 mSv with a radiation-attenuating drape, with the recommended limit being 20 mSv.CONCLUSIONS:The addition of a radiation-attenuating drape around the image intensifier during ERCP significantly decreases radiation exposure to endoscopists and staff by ∼90%.

PANCREATITIS OR NOT? – Elevated lipase and amylase in ICU patients

Elevation in serum levels of pancreatic enzymes (Hyperamylasemia and/or Hyperlipasemia) can occur in any Intensive Care Unit (ICU) patient either as a result of true acute pancreatitis (AP) or as a reflection of a non-pancreatic disease. Although most patients may not have clinical pancreatitis, identifying true acute pancreatitis in the ICU setting may be critical in the presence of associated co-morbid conditions of the disease for which the patient is being managed. With neither amylase nor lipase being specific for pancreatitis, it is important for the clinician to be aware of different causes of hyperamylasemia and hyperlipasemia, especially when clinical diagnosis of pancreatitis is unclear. This review will focus on understanding different non-pancreatic conditions where there is elevation of pancreatitis enzymes and to identify true acute pancreatitis in critically ill patients without typical symptoms.