Risk factors for intraductal papillary mucinous neoplasm (IPMN) of the pancreas: a multicentre case-control study.

OBJECTIVES: To investigate environmental, personal, and hereditary risk factors associated with the occurrence of intraductal papillary mucinous neoplasms of the pancreas (IPMNs). METHODS: Multicentre case-control study. Risk factors were identified from a questionnaire collecting data on family and medical history, and environmental factors. Cases were prevalent IPMNs seen at the participating units within an 18-month timeframe. Matched controls were enrolled alongside patients seen at outpatient clinics. RESULTS: Three-hundred and ninety patients with IPMN and 390 matched controls (166 males, mean age 65 in each group) were enrolled. Of the IPMNs, 310 had branch-duct involvement and 80 main-duct involvement. The only cancer with a 1st degree family history significantly higher in IPMN was pancreatic ductal adenocarcinoma (PDAC) (5.4% vs. 1.5%). Previous history of diabetes (13.6% vs. 7.5%), chronic pancreatitis (CP) (3.1% vs. 0.3%), peptic ulcer (7.2% vs. 4.3%), and insulin use (4.9% vs. 1.1%) were all more frequent with IPMNs. Logistic regression multivariate analysis revealed that history of diabetes (odds ratio (OR): 1.79, confidence interval (CI) 95%: 1.08-2.98), CP (OR: 10.10, CI 95%: 1.30-78.32), and family histories of PDAC (OR: 2.94, CI 95%: 1.17-7.39) were all independent risk factors. However, when analysis was restricted to diabetics who had taken insulin, risk of IPMN became stronger (OR: 6.03, CI 95%: 1.74-20.84). The association with all these risk factors seemed stronger for the subgroup with main duct involvement. CONCLUSIONS: A previous history of diabetes, especially with insulin use, CP, and family history of PDAC are all relevant risk factors for the development of IPMN. These results suggest an overlap between certain risk factors for PDAC and IPMN.

Ki-67 grading of nonfunctioning pancreatic neuroendocrine tumors on histologic samples obtained by EUS-guided fine-needle tissue acquisition: a prospective study.

BACKGROUND: Preoperative determination of Ki-67 expression, an important prognostic factor for grading nonfunctioning pancreatic endocrine tumors (NF-PETs), remains an important clinical challenge. OBJECTIVE: To prospectively evaluate the feasibility, yield, and clinical impact of EUS-guided fine-needle tissue acquisition (EUS-FNTA) with a large-gauge needle to obtain tissue samples for histologic diagnosis and Ki-67 analysis in patients with suspected NF-PETs. DESIGN: Prospective cohort study. SETTING: Tertiary-care academic medical center. PATIENTS: Consecutive patients with a single pancreatic lesion suspicious for NF-PET on imaging. INTERVENTION: EUS-FNTA with a 19-gauge needle. MAIN OUTCOME MEASUREMENTS: Feasibility and yield of EUS-FNTA for diagnosis and Ki-67 expression determination. RESULTS: Thirty patients (mean [± SD] age 55.7 ± 14.9 years), with a mean (± SD) lesion size of 16.9 ± 6.1 mm were enrolled. EUS-FNTA was successfully performed without complications in all patients, with a mean (± SD) of 2.7 ± 0.5 passes per patient. Adequate samples for histologic examination were obtained in 28 of the 30 patients (93.3%). Ki-67 determination could be performed in 26 of these 28 patients (92.9%, 86.6% overall), 12 of whom underwent surgical resection. Preoperative and postoperative Ki-67 proliferation indexes were concordant in 10 patients (83.3%), whereas 2 patients were upstaged from G1 to G2 or downstaged from G2 to G1, respectively. LIMITATIONS: Single center study with a single operator. CONCLUSION: In patients with suspected nonfunctioning low-grade to intermediate-grade pancreatic neuroendocrine tumors (p-NETs), retrieval of tissue specimens with EUS-FNTA by using a 19-gauge needle is safe, feasible, and highly accurate for both diagnosis and Ki-67 determination. A Ki-67 proliferative index acquired through this technique might be of great help for further therapeutic decisions.

EUS-guided fine-needle tissue acquisition by using a 19-gauge needle in a selected patient population: a prospective study.

BACKGROUND: The ability to obtain tissue samples for histological examination during EUS has theoretical advantages over cytology alone. OBJECTIVE: To prospectively evaluate the feasibility and yield of EUS-guided fine-needle tissue acquisition (EUS-FNTA) with a large-gauge needle in patients in whom we expected histology to be more useful than cytology to reach a definitive diagnosis. DESIGN: Prospective cohort study. SETTING: Tertiary care academic medical center. PATIENTS: Consecutive patients with subepithelial lesions, esophagogastric wall thickening, mediastinal and abdominal masses/lymphadenopathy of unknown origin, or pancreatic lesions after nondiagnostic FNA. INTERVENTIONS: EUS-FNTA with a 19-gauge needle. MAIN OUTCOME MEASUREMENTS: Feasibility and yield of EUS-FNTA. RESULTS: A total of 120 patients with a mean age of 61 ± 14.6 years and mean lesion size of 38 ± 25 mm (range 8-140 mm) were enrolled. FNTA was successfully performed in all but 1 patient (98.9%), and adequate samples for histological examination were obtained in 116 of the 119 patients (97.5%) in whom EUS-FNTA was technically successful. A mean of 2.8 ± 0.8 passes per patient were performed. At the time of current follow-up, a definitive diagnosis was available in 117 of the 120 patients (97.5%), with only 8 false-negative results. The sensitivity, specificity, positive and negative predictive values, and diagnostic accuracy of EUS-FNTA in the 117 patients with a definitive diagnosis were 91.8%, 100%, 100%, 71.4%, and 93.2%, respectively. LIMITATIONS: Single-center study with limited power. CONCLUSIONS: EUS-FNTA by using a large-gauge needle has a high yield and promising diagnostic accuracy and could be used when histology may be more useful than cytology to reach a definitive diagnosis.

Alteration of local microflora and α-defensins hyper-production in colonic adenoma mucosa.

BACKGROUND AND AIM: Gut flora/host interactions are fundamental for the maintenance of homeostasis. Evidence of possible regulatory effect of commensal bacteria on proliferative disorders of the colon is mounting. In this study, we explored the hypothesis that precancerous lesions, such as adenomas, present alteration of the local microflora and lead to an overproduction of antibacterial molecules of the innate immunity, namely α-defensins. Thus, the host-bacteria misbalance could represent a potential procarcinogenic factor. METHODS: Biopsies from adenomatous polyps and normal mucosa, in the rectum-sigmoid colon, were collected from 51 patients. Concentration of mucosal bacteria was evaluated by real-time polymerase chain reaction after extraction of total DNA. Total RNA was also extracted, and the defensin α-1, defensin-5, and defensin-6 gene expressions were evaluated by real-time polymerase chain reaction. Immunohistochemical study has been carried out to evaluate protein production and location. Antibacterial activity of adenomatous polyps mucosa was evaluated in vitro. RESULTS: Biopsies from adenomatous polyps had a significant relative reduction of mucosa adherent bacteria compared with normal tissue (20-fold relative reduction, P<0.05). Concomitantly, α-defensin expression and production were significantly increased in adenomas. Adenoma mucosa showed increased antibacterial activity in vitro compared with normal mucosa. CONCLUSIONS: Microflora dysbiosis occurs at the mucosal surface in colonic adenomas, and may represent a potential factor for dysplastic cell proliferation. Further studies are needed to confirm and define the role of this mechanism in colon carcinogenesis and the potential applications in the clinical setting.

A case of oesophageal ulcer developed after taking homeopathic pill in a young woman.

Oesophageal ulcers occur mainly as a result of gastro-oesophageal reflux disease (GERD). However, pill-induced oesophageal ulcers are a fairly common event. The lesion is mainly due to entrapment of the pill and/or its chemical composition thereof. This case report describes an oesophageal mucosa ulcer occurred in a healthy 35-year old woman who had no previous history of oesophageal disorders and received homeopathic medication. The present case reveals that pill entrapment can occur even in the oesophagus of healthy young individuals and that oesophageal mucosal ulcer can be triggered by substances generally thought devoid of any potentially mucosal aggressive effect.

Is colonoscopy sufficient for colorectal cancer surveillance in all HNPCC patients?

A 34-year-old male with hereditary non-polyposis colon cancer with a mutation in hMSH2 line is reported. Despite regular colonoscopic follow-up, he developed cecal cancer involving the extraluminal area. Due to sub-occlusive symptoms, the patient was submitted to further colonoscopy, however with no clear evidence of neoplasia. Thin slice multiplanar reconstruction computed tomography CT scan performed thereafter revealed a transmural mass 2.5 cm in size localized near the cecal valve. Discussion is made on the reliability of colonoscopic examinations as well as the need for further investigations in the follow-up of patients at very high risk of right-sided colon cancer, such as male hMSH2 carrier affected by hereditary non-polyposis colon cancer.

Endoscopic ultrasound-guided fine-needle aspiration with liquid-based cytologic preparation in the diagnosis of primary pancreatic lymphoma.

OBJECTIVES: The diagnosis subtyping of lymphoma on specimens collected by endoscopic ultrasound fine-needle aspiration (EUS-FNA) can be extremely difficult. When a cytopathologist is available for the on-site evaluation, the diagnosis may be achieved by applying flow cytometric techniques. We describe our experience with immunocytochemistry (ICC) and molecular biology studies applied on EUS-FNA specimens processed with a liquid-based cytologic (LBC) preparation for the diagnosis of primary pancreatic lymphoma (PPL). METHODS: Three patients with a pancreatic mass underwent EUS-FNA. The collected specimens were processed with the ThinPrep method for the cytologic diagnosis and eventual additional investigations. RESULTS: A morphologic picture consistent with PPL was found on the LBC specimens of the 3 patients. Subsequent ICC and molecular biology studies for immunoglobulin heavy chain gene rearrangement established the diagnosis of pancreatic large B-cell non-Hodgkin lymphoma in 2 patients and a non-Hodgkin lymphoma with plasmoblastic/immunoblastic differentiation in the remaining one. CONCLUSIONS: An LBC preparation can be used to diagnose and subtype PPL by applying ICC and molecular biology techniques to specimens collected with EUS-FNA. This method can be an additional processing method for EUS-FNA specimens in centers where on-site cytopathologist expertise is not available.