Marcia Cruz-Correa

Lymphoplasmacytic chronic cholecystitis and biliary tract disease in patients with lymphoplasmacytic sclerosing pancreatitis

Lymphoplasmacytic sclerosing pancreatitis (LPSP) represents a distinctive form of chronic pancreatitis characterized by diffuse fibroinflammatory infiltrates that can involve both the pancreatic ducts and acinar parenchyma. Several cases of inflammatory infiltrates within the gallbladder have been reported in association with LPSP, but the spectrum of gallbladder pathology in patients with LPSP has not been systematically reviewed. Many patients with LPSP have distal CBD fibrosis, strictures, and inflammation, features that overlap somewhat with primary sclerosing cholangitis (PSC). In PSC, a pattern of gallbladder pathology termed “diffuse acalculous lymphoplasmacytic chronic cholecystitis” has been previously described as showing a triad of diffuse, mucosal-based, plasma cell-rich inflammatory infiltrates. We studied 20 gallbladders from patients with LPSP and compared them with 20 gallbladders in PSC, 20 gallbladders with chronic cholelithiasis, and 10 gallbladders from patients with benign (non-LPSP) pancreatic disease. The following features were evaluated: degree and composition of mucosal inflammation and deep (mural) inflammation, lymphoid nodules, metaplasia, dysplasia/neoplasia, fibrosis, muscular hypertrophy, Rokitansky-Aschoff sinuses, and cholesterolosis. The majority (60%) of gallbladders in LPSP contained moderate or marked inflammatory infiltrates and lymphoid nodules, frequencies similar to PSC but significantly higher than in chronic cholelithiasis and benign non-LPSP pancreatic disease. LPSP gallbladders received the highest scores for deep inflammation of all groups, and 35% of LPSP gallbladders showed transmural chronic cholecystitis. Overall, “diffuse lymphoplasmacytic chronic cholecystitis” was present in 50% of PSC cases and 25% of LPSP cases, but in only 5% of chronic cholelithiasis and none of non-LPSP benign pancreatic disease. Mucosal inflammation in LPSP gallbladders correlated significantly with the presence of inflammation in the extrapancreatic portion of the CBD. These findings suggest that inflammatory pathology of the gallbladder is frequently associated with LPSP and that it is part of the spectrum of biliary tract disease in these patients, rather than a simple reflection of the pancreatitis itself.

Sporadic fundic gland polyposis: A clinical, histological, and molecular analysis

Sporadic fundic gland polyposis (SFGP) is defined as multiple fundic gland polyps in patients without familial adenomatous polyposis syndrome (FAP). Although little is known about the genetic changes in SFGP, mutations in the Wnt signaling pathway have been recently linked to fundic gland polyps in other settings: sporadic polyps are linked to activating β-catenin mutations, whereas FAP-associated fundic gland polyps are caused by second somatic hits in the adenomatous polyposis coli gene. The relationship between SFGP, single sporadic fundic gland polyps, and FAP-associated polyps remains unclear, and SFGP remain poorly characterized at the clinical, histological, and molecular levels. A retrospective study was undertaken of eight patients with SFGP who had ≥10 polyps with at least five endoscopic biopsy specimens available for study. One additional patient with attenuated FAP who underwent partial gastrectomy was included as a control. The medical records and biopsy specimens were reviewed. Mutations of the β-catenin gene were evaluated in each fundic gland as well as in control nonpolypoid tissue by direct sequencing of a mutational hot spot in exon 3 of the β-catenin gene, which encodes the GSK-3β phosphorylation sites, and a HinfI endonuclease digestion assay. The four men and four women in the study were an average of 57 years of age at biopsy. All patients were on acid-suppression therapy, 5/8 with proton-pump inhibitors (PPI) and 3/8 with Zantac. Sixty-two polyps were studied, and all were <10 mm, with most between 2 and 7 mm. The polyps were histologically identical to single sporadic fundic gland polyps. No dysplasia was seen. Forty-seven of 62 polyps (76%) had detectable β-catenin mutations. Mutations were found in all eight of the patients. All were point mutations in codons 32, 33, 34, and 37 and are either phosphorylation sites or immediately adjacent to phosphorylation sites, findings identical to that seen in single sporadic fundic gland polyps. Each polyp had a single mutation, and each patient had more than one unique mutation (median = 4), indicating a multifocal origin for the polyps. No mutations were found in nonpolypoid control tissue and in polyps from the attenuated FAP patient. The patients with SFGP in this series were all between 40 and 70 years of age and had histories of acid-suppressive therapy. The fundic gland polyps were histologically and genetically identical to single sporadic fundic gland polyps and demonstrated frequent somatic activating mutations in exon 3 of the β-catenin gene.

Diffuse lymphoplasmacytic chronic cholecystitis is highly specific for extrahepatic biliary tract disease but does not distinguish between primary and secondary sclerosing cholangiopathy

Previous studies of gallbladder pathology in primary sclerosing cholangitis (PSC) have suggested that a distinctive histologic triad (“diffuse lymphoplasmacytic acalculous cholecystitis,” composed of diffuse, mucosal-based, dense lymphoplasmacytic infiltrates) is commonly present in gallbladders of patients with PSC and is relatively specific for that disease. However, prior control populations have included only patients with cholecystitis/cholelithiasis and hepatitis, and have not evaluated patients with non-PSC-associated extrahepatic biliary tract disease. We recently observed cases of diffuse lymphoplasmacytic chronic cholecystitis in a subset of patients with biliary tract disease associated with lymphoplasmacytic sclerosing pancreatitis and among patients undergoing Whipple resection for pancreatic head malignancy, suggesting that diffuse lymphoplasmacytic chronic cholecystitis is not specific for PSC. We studied 20 gallbladders from patients with obstructive jaundice due to malignancies of the pancreatic head, duodenum, or ampulla and 5 gallbladders from patients with choledocholithiasis, and compared them with 20 gallbladders from patients with PSC and 20 gallbladders with cholelithiasis. The following histologic features were evaluated: degree of mucosal and deep inflammation, lymphoid nodules, epithelial metaplasia, muscular hypertrophy, Rokitansky-Aschoff sinuses, fibrosis, and cholesterolosis. Gallbladders in malignancy-associated obstructive jaundice were nearly identical to gallbladders in PSC with respect to scores for mucosal inflammation, lymphoid nodules, and frequency of diffuse lymphoplasmacytic chronic cholecystitis (60% vs. 50%, respectively). PSC gallbladders, however, were significantly more likely to contain focal or extensive epithelial metaplasia (P = 0.01). The cholelithiasis control group was characterized by lack of significant mucosal inflammation in the majority of cases (95%) and frequent Rokitansky-Aschoff sinuses, fibrosis, and muscular hypertrophy. Gallbladders in the choledocholithiasis group showed overlapping histologic features with PSC/malignancy-associated obstructive jaundice and cholelithiasis. These results suggest that a pattern of diffuse lymphoplasmacytic chronic cholecystitis is highly specific for extrahepatic biliary tract disease but does not distinguish between primary and secondary cholangiopathies.

A long-term cohort study of outcome after cholecystectomy for chronic acalculous cholecystitis.

BACKGROUND Cholecystectomy is effective therapy for chronic calculous cholecystitis (CCC). The long-term outcome of patients treated with cholecystectomy for chronic acalculous cholecystitis (CAC) is unknown. METHODS A controlled, retrospective cohort study assessing biliary pain (preoperative and at follow-up) in postcholecystectomy patients with CAC or CCC was performed. RESULTS In 19 CAC and with matched CCC control patients, the mean duration of symptoms before surgery was 38.3 months (95% CI, 16.4 to 60.2) and 8.1 months (95% CI, 5.4 to 10.8), respectively. The mean follow-up for both groups was 8.37 +/- 1.13 years. Both groups benefited from cholecystectomy (P <0.001), and both were equally likely to be pain-free upon long-term follow-up (95% CAC versus 84% CCC, P >0.05). CONCLUSIONS There was no difference in outcome between the groups after an average follow-up of 8.37 years. Postcholecystectomy patients with chronic cholecystitis and no gallstones have long-term, complete pain resolution, similar to patients with gallstones.

Intrasphincteric Nitric Oxide Reduces Sphincter of Oddi Motility in an Endoscopic Porcine Model

Nitric oxide (NO), a potent nonadrenergic, noncholinergic mediator of gastrointestinal smooth muscle, causes relaxation of the category I pump like sphincter of Oddi (SO) (eg, opossum, rabbit) and category II resistor like SO (eg, pig, human). Topical administration of a NO donor induces SO relaxation in humans, and parenteral administration of sodium nitroprusside (SNP) decreases sphincter contractility in pig SO. The aim of this study is to evaluate the effect of intrasphincteric SNP injection on pig SO. Under general anesthesia, two pigs received intrasphincteric saline injection (1 ml) and six pigs received intrasphincteric SNP (0.5 μg/ml) injection into the SO. All injections were administered into the major papilla using a 5-mm sclerotherapy needle through the duodenoscope. Endoscopic biliary manometry was performed using the standard station pull-through technique and SO pressures were recorded before and after injection. Intrasphincteric saline injection did not significantly change the mean SO motility index (MI) (197 vs 198). However, intrasphincteric SNP reduced both the mean SO basal pressure (P = 0.002) and the mean SO MI (226 vs 109; P = 0.002). The effect of intrasphincteric SNP lasted up to 45 min and did not cause significant lowering of systemic blood pressure. This is the first study to demonstrate that intrasphincteric SNP results in significant reduction in both SO basal pressure and SO MI in the porcine model. The endoscopic intrasphincteric administration of NO donor drugs is technically feasible and without observed systemic side effects.

The impact of practice guidelines on management of Barrett's esophagus: a prospective cohort

The impact of practice guidelines on management of Barretts esophagus: a prospective cohort

Women Gastroenterologists in Academic Medicine: Tradition Versus Transition

Most women experience childhood dreams of being a grownup, with a pretty house with a white picket fence and children running around. That same little girl wanted to be a doctor; she grew up and had to face the reality that life is more complex than her dreams and that being a female gastroenterologist in this era is a multifaceted endeavor. Gastroenterology as a specialty offers the opportunity to provide long-term care to our patients and enjoy the technical aspects of endoscopy and other procedures. Until as recently as 1990, fewer than 5% of gastroenterologists were women, possibly due to the perception at the time that the practice of gastroenterology was associated with long and irregular hours, frequent night call, harsh physical strength, and quite frankly, working with aesthetically challenging bodily emanations. Recently, when more women started to consider gastroenterology as a subspecialty, there was also increased interest by women in technology, a gender shift that may reflect changes in women’s places in society. Nevertheless, since gastroenterology remains a physically and intellectually demanding subspecialty, conflicts between personal and career goals arise as women transition from fellowship to practice. It is expected that as women struggle to balance family and career, the discovery of new approaches to traditional women’s contributions toward academic gastroenterology and career pathways is warranted.

Report of a PMS2 Germline Mutation Patient Presenting with Endometrial and Parotid Cancer

Colorectal cancer (CRC) is the second leading cause of cancer among men and women and represents the leading cause of cancer death in Puerto Rico. Familial CRC accounts for 10-15% of the total CRC cases, with Lynch syndrome (LS) implicated in 2-4% of cases. Limited information is available on the prevalence, clinical manifestations, and genetic mutations of hereditary CRC in USA Hispanics. In this paper we report a PMS2 mutation in a Puerto Rican Hispanic patient with LS recruited through the Puerto Rico Familial Colorectal Cancer Registry. At the age of 35 years our proband was diagnosed with endometrial cancer with parotid cancer established the following year. A diagnosis of Lynch Syndrome was established through analysis of protein expression by immunohistochemistry and genetic sequencing of mismatch repair genes. Mutation in the PMS2 gene is rarely linked with LS. This case report adds Parotid Carcinoma to the spectrum of malignant conditions associated to LS. We emphasize on the importance of genetic testing in at-risk patients for hereditary CRC from various racial backgrounds, and underscore the need for genetic counselling of patients and their family members. Recognition of LS carriers will allow early detection of malignant condition and the implementation of effective therapy, which will ultimately improve prognosis.

45 – Gender Difference in Gastrointestinal Endoscopy

Gastrointestinal (GI) endoscopy is a diagnostic and therapeutic procedure that allows imaging, assessing, and treating GI illnesses. Careful review of the available literature allows identification of important gender differences associated with the indications, performance, outcome, and risks for GI endoscopy. This chapter presents an overview of endoscopic techniques, examines current data regarding gender differences related to each major endoscopic procedure, and highlights specific issues pertaining to the performance of endoscopy in a pregnant patient. Women may be less tolerant to both sedated and unsedated colonoscopy and are more likely to describe colonoscopy as painful or uncomfortable. Women may be less satisfied with conscious sedation than men, although firm conclusions cannot be reached due to the limited amount of data available. Patient tolerance of both sedated and unsedated upper endoscopy (EGD) has been assessed. There are no major gender differences in tolerability, technique, or equipment use during endoscopic retrograde cholangiopancreatography (ERCP). Only highly trained personnel should perform ERCP during pregnancy, and its use should be limited to the treatment of threatening medical conditions including cholelithiasis complicated by jaundice, impacted choledocholithiasis, pancreatitis, or cholangitis. The reason that endoscopic ultrasound (EUS) does not expose the fetus to ionizing radiation, it may have an important role in the management of biliary, gallbladder disease, and cancer staging during pregnancy.