Intraductal papillary mucinous neoplasm of the intrahepatic bile duct: a review of literature and a rare case report.

Background: Intraductal papillary neoplasm of the bile duct is a rare variant of bile duct tumors, which is characterized by papillary or villous growth inside the bile duct. Having papillary and mucinous features such as those found in pancreatic intraductal papillary mucinous neoplasm (IPMN) is extremely rare. We report a rare case of intraductal papillary mucinous neoplasm of the intrahepatic bile duct. Case report: A 65-year-old male Caucasian with multiple comorbidities presented to the emergency room with moderate constant pain at the right upper quadrant (RUQ) abdomen for the last several hours. On physical examination, he was found to have normal vital signs, with icteric sclera and pain on deep palpation at the RUQ region. His laboratory results were significant for jaundice, elevated liver function tests and creatinine, hyperglycemia, and leukocytosis. Multiple imaging studies revealed a 5 cm heterogeneous mass in the left hepatic lobe that demonstrated areas of internal enhancement, mild gall bladder wall edema, dilated gall bladder with mild sludge, and 9 mm common bile duct (CBD) dilatation without evidence of choledocholithiasis. He underwent a CT-guided biopsy of this mass, which revealed intrahepatic papillary mucinous neoplasm. This case was discussed at the hepatobiliary multidisciplinary conference, and the patient underwent an uneventful robotic left partial liver resection, cholecystectomy, and lymphadenectomy. Conclusion: IPMN of the biliary tract may represent a carcinogenesis pathway different from that of CBD carcinoma arising from flat dysplasia. Complete surgical resection should be performed whenever possible because of its significant risk of harboring invasive carcinoma.

Distinction between Mitochondrial Antibody-Positive and -Negative Primary Biliary Cholangitis.

Antimitochondrial antibody-positive primary biliary cholangitis (AMA-pos PBC) is an autoimmune disorder in which monoclonal antibodies are produced against epitopes in the mitochondrial membranes of biliary epithelial cells, resulting in progressive nonsuppurative biliary cholangitis. Up to 5% of patients lack these autoantibodies, termed antimitochondrial antibody-negative (AMA-neg) PBC. Although a somewhat new variant of AMA-pos PBC, it is not an overlapping syndrome. Few studies to date have described this phenomenon. An 87-year-old woman was referred to our clinic with elevated serum alkaline phosphatase (714 U/L). She reported fatigue but no other symptoms. A physical examination revealed a benign lesion and bilateral lower extremity swelling secondary to lymphedema. The serological profile was significant for a high antinuclear antibody titer (>1:2,560) with a centromere pattern and negative for antimitochondrial antibody (AMA). The hepatitis panel was negative for viruses A, B, and C. Her serum immunoglobulin G level was 871 mg/dL (normal, <1,600 mg/dL). The rest of the serological tests, including anti-smooth muscle antibodies (ASMA) and anti-liver/kidney microsomal antibodies, were negative. Computed tomography of the abdomen and pelvis without contrast showed normal liver parenchyma and no acute intra-abdominal pathology. Histopathology indicated florid duct lesions. The background parenchyma showed no significant steatosis, and inflammatory changes were limited to the portal areas. Periodic acid-Schiff staining revealed intact hepatic parenchyma and architecture. The patient was diagnosed with AMA-neg PBC and responded well to ursodeoxycholic acid therapy. This case highlights the importance of recognizing AMA-neg PBC as a variant of AMA-pos PBC and differentiating between them. Autoimmune cholangitis is a vague and imprecise condition. All patients with AMA-negative PBC should be tested for other PBC-specific autoantibodies. Although the prognosis and bile duct damage and loss are worse in AMA-neg PBC for unknown reasons, treatment remains the same for both.

A rare synchrony of adenocarcinoma of the ampulla with an ileal gastrointestinal stromal tumor: A case report.

BACKGROUND: This is a unique case of a patient who was found to have two extremely rare primary malignancies synchronously, i.e., an ampullary adenocarcinoma arising from a high-grade dysplastic tubulovillous adenoma of the ampulla of Vater (TVAoA) with a high-grade ileal gastrointestinal stromal tumor (GIST). Based on a literature review and to the best of our knowledge, this is the first report of this synchronicity. Primary ampullary tumors are extremely rare, with an incidence of four cases per million population, which is approximately 0.0004%. Distal duodenal polyps are uncommon and have a preponderance of occurring around the ampulla of Vater. An adenoma of the ampulla ( AoA) may occur sporadically or with a familial inheritance pattern, as in hereditary genetic polyposis syndrome such as familial adenomatous polyposis syndrome (FAPS). We report a case of a 77-year-old male who was admitted for painless obstructive jaundice with a 40-pound weight loss over a two-month period and who was subsequently diagnosed with two extremely rare primary malignancies, i.e., an adenocarcinoma of the ampulla arising from a high-grade TVAoA and a high-grade ileal GIST found synchronously. CASE SUMMARY: A 77-year-old male was admitted for generalized weakness with an associated weight loss of 40 pounds in the previous two months and was noted to have painless obstructive jaundice. The physical examination was benign except for bilateral scleral and palmar icterus. Lab results were significant for an obstructive pattern on liver enzymes. Serum lipase and carbohydrate antigen-19-9 levels were elevated. Computed tomography (CT) of the abdomen and pelvis and magnetic resonance cholangiopancreatography were consistent with a polypoid mass at the level of the common bile duct (CBD) and the ampulla of Vater with CBD dilatation. The same lesions were visualized with endoscopic retrograde cholangiopancreatography. Histopathology of endoscopic forceps biopsy showed TVAoA. Histopathology of the surgical specimen of the resected ampulla showed an adenocarcinoma arising from the TVAoA. Abdominal and pelvic CT also showed a coexisting heterogeneously enhancing, lobulated mass in the posterior pelvis originating from the ileum. The patient underwent ampullectomy and resection of the mass and ileo-ileal side-to-side anastomosis followed by chemoradiation. Histopathology of the resected mass confirmed it as a high-grade, spindle cell GIST. The patient is currently on imatinib, and a recent follow-up positron emission tomography (PET) scan showed a complete metabolic response. CONCLUSION: This case is distinctive because the patient was diagnosed with two synchronous and extremely rare high-grade primary malignancies, i.e., an ampullary adenocarcinoma arising from a high-grade dysplastic TVAoA with a high-grade ileal GIST. An AoA can occur sporadically and in a familial inheritance pattern in the setting of FAPS. We emphasize screening and surveillance colonoscopy when one encounters an AoA in upper endoscopy to check for FAPS. An AoA is a premalignant lesion, particularly in the setting of FAPS that carries a high risk of metamorphism to an ampullary adenocarcinoma. Final diagnosis should be based on a histopathologic study of the surgically resected ampullary specimen and not on endoscopic forceps biopsy. The diagnosis of AoA is usually incidental on upper endoscopy. However, patients can present with constitutional symptoms such as significant weight loss and obstructive symptoms such as painless jaundice, both of which occurred in our patient. Patient underwent ampullectomy with clear margins and ileal GIST resection. Patient is currently on imatinib adjuvant therapy and showed complete metabolic response on follow up PET scan.

Taste Perceptions of Common Pediatric Antibiotic Suspensions and Associated Prescribing Patterns in Medical Residents.

OBJECTIVE: Palatability of medication is an important factor for adherence, especially in pediatric populations that tend to use oral suspensions for antibiotic therapy. Our study is the first to evaluate the impact of taste on prescribing patterns of antibiotic suspensions. The objective was to determine if taste testing common antibiotic suspensions altered prescribing patterns of medical residents, through data extracted from the electronic health record. METHODS: After assessing 5 "primer" tastes (sweet, salty, bitter, sour, umami [savory]), residents were randomized to sample 6 antibiotic suspensions to rate their taste perception. A 12-month retrospective and prospective analysis of outpatient prescribing practices of the residents followed, and the results were compared to the resident cohort randomized to no taste test. RESULTS: The 43 residents prescribed 207 liquid antibiotic prescriptions for 176 patients, with no difference in patient characteristics between residents in the taste test versus non-taste test group. Although amoxicillin was most preferable and amoxicillin-clavulanate least, the only significant finding was a greater prescribing rate of cefdinir among those who had tasted it and an inverse relationship between cephalexin taste preference and percentage prescribing amoxicillin in the taste group. Residents who tasted were poor in identifying primer tastes, but this did not impact prescribing patterns. CONCLUSIONS: Among 6 commonly prescribed antibiotic suspensions, amoxicillin remains a highly preferred taste among prescribers. Interestingly, after the taste test there was a significantly greater prescribing rate of cefdinir among those who had tasted it and somewhat lower prescribing rate for amoxicillin-clavulanate.

Ampullary and Pancreatic Neuroendocrine Tumors: A Series of Cases and Review of the Literature.

The ampulla of Vater is a unique, highly vascularized pouch. Its anatomic transition is halfway along the second part of the duodenum from the foregut to the midgut. According to the World Health Organization's (WHO) latest nomenclature, carcinoid tumors are now called neuroendocrine tumors (NETs). Knowledge of NETs is important because of their rarity, reclassification, prognosis, and management. NETs involving the ampulla of Vater are extremely rare, constituting <0.05% of gastrointestinal NETs, and involving the pancreas are rare to our knowledge. There are only a few reports of ampullary NETs. We report two rare NET cases involving the ampulla and pancreas and review the relevant literature. A 71-year-old patient with neurofibromatosis and multiple comorbidities presented with chronic intermittent abdominal pain. Abdominal imaging studies showed a suspicious mass at the level of the ampulla. Endoscopic retrograde cholangiopancreatography and endoscopic ultrasound revealed bulging papillae. Histopathology of the biopsied mass revealed a low-grade NET. Given his multiple comorbidities, the patient was scheduled for endoscopic resection. Our second patient was an 83-year-old lady presenting with nausea and vomiting. Abdominal imaging studies revealed a lobular mass over the body of the pancreas. Histopathological examination of fine-needle aspiration of the mass confirmed a well-differentiated low-grade NET. Octreoscan and dotatate scans showed pancreatic, multiple hepatic and metastatic lesions in the left lung and left shoulder. The patient is currently stable after completing peptide receptor radioligand therapy at a tertiary oncology center. Because of the patients' comorbidities and staging, their management has taken different approaches. More data and more research are needed for accurate assessment of prognosis; however, a review of the latest literature recommends Whipple resection with lymphadenectomy for all ampullary NETs provided patients can tolerate the procedure. Endoscopic resection or surgical ampullary resection should be performed on contraindicated patients. The majority of ampullary and pancreatic NETs would have metastasized by the time patients sought treatment. Because of their rarity and ill-defined and highly variable presentation, NET diagnosis is always delayed and sometimes incidental; therefore, we emphasize the importance of early diagnosis and management to reduce mortality and morbidity.

The Effects of Bar-coding Technology on Medication Errors: A Systematic Literature Review.

BACKGROUND: The bar-coding technology adoptions have risen drastically in U.S. health systems in the past decade. However, few studies have addressed the impact of bar-coding technology with strong prospective methodologies and the research, which has been conducted from both in-pharmacy and bedside implementations. OBJECTIVE: This systematic literature review is to examine the effectiveness of bar-coding technology on preventing medication errors and what types of medication errors may be prevented in the hospital setting. METHODS: A systematic search of databases was performed from 1998 to December 2016. Studies measuring the effect of bar-coding technology on medication errors were included in a full-text review. Studies with the outcomes other than medication errors such as efficiency or workarounds were excluded. The outcomes were measured and findings were summarized for each retained study. RESULTS: A total of 2603 articles were initially identified and 10 studies, which used prospective before-and-after study design, were fully reviewed in this article. Of the 10 included studies, 9 took place in the United States, whereas the remaining was conducted in the United Kingdom. One research article focused on bar-coding implementation in a pharmacy setting, whereas the other 9 focused on bar coding within patient care areas. All 10 studies showed overall positive effects associated with bar-coding implementation. CONCLUSIONS: The results of this review show that bar-coding technology may reduce medication errors in hospital settings, particularly on preventing targeted wrong dose, wrong drug, wrong patient, unauthorized drug, and wrong route errors.

Attitudes of Michigan Female College Students About Pharmacists Prescribing Birth Control in a Community Pharmacy.

In the United States, the overall unintended pregnancy rate is about 45%. Women between 20-24 years old account for 59% of the unintended pregnancies. Continuous birth control use is related to decreasing unintended pregnancies. Therefore, we assessed female college students' opinions about pharmacists prescribing birth control in a community pharmacy using an intersectionality framework. A survey with 49 items about provider attributes, pharmacy services use and evaluation, advantages and barriers of pharmacists prescribing birth control, sexual and reproductive history, and demographics was distributed by survey link and QR code. Recruitment was done by investigators and students (snowballing technique) via emails, social media posts, and direct student contact. Respondents (n = 859) were 23.0 ± 4.9 years old, 83% white, 64% healthcare students, 32% student pharmacists, 69% sexually active, 68% with at least one episode of unprotected intercourse within a year, and 29% never using condoms. Forty-six percent of students were extremely likely and 26% moderately likely to get birth control from a pharmacist because it would be easier to adhere to birth control, could prevent unintended pregnancies, would be more convenient, and require less time. Concerns included the lack of Pap screenings and prescriptions written for the wrong birth control. Within most student characteristics or attitudes assessed, at least 70% of the students would use this service. Based on student opinions, female college students would use pharmacists prescribing birth control services.

Incidental liver metastasis in pancreatic adenocarcinoma.

Exocrine cancer of pancreas is the fourth leading cause of death in the USA among both men and women. Contrast enhanced multidetector-row computer tomography (MDCT) is the current modality of choice for the detection of distant metastasis in pancreatic cancer as a part of pre-operative workup, which helps decide on resectability. Authors present a first ever reported case of an incidental liver metastasis found on intra-operative wedge hepatic biopsy during Whipple's procedure for pancreatic cancer. This pancreatic cancer was initially thought to be resectable based on MDCT staging per guidelines. The case highlights the importance of diagnostic staging laparoscopy and neoadjuvant chemotherapy before resecting pancreatic adenocarcinoma.

Ganciclovir-Resistant CMV Colitis in a Donor-Seronegative/Recipient-Seronegative Liver Transplant Patient.

Cytomegalovirus (CMV) disease in liver transplant patients with donor-seronegative and recipient-seronegative (D-/R-) status is a rarity. Ganciclovir-resistant CMV disease in this population has not been reported in the literature. We present a 62-year-old man who underwent orthotopic liver transplant from a cadaveric donor. The patient's status was CMV D-/R-, and he had completed 90 days of valganciclovir therapy for CMV prophylaxis, yet he developed CMV disease. We highlight the danger of the liberal use of CMV prophylaxis in this subset of the liver transplant population. To our knowledge, this is the first report of ganciclovir-resistant (GanR) CMV disease in a liver transplant patient with CMV D-/R- status.

Curative resection of pancreatic adenocarcinoma with major venous resection/repair is safe procedure but will not improve survival.

OBJECTIVE: To evaluate the safety and survival benefit of combined curative resection (CR) of the pancreas and major venous resection in the management of borderline resectable pancreatic adenocarcinoma. METHODS: In this IRB approved retrospective cohort study, patients who had pancreatic surgery (n=274) between 1998-2012 were reviewed. One hundred and seventy-five patients had malignant causes, of which 119 underwent CR. One hundred and two patients who did not require venous resection/repair (Group-I) were compared with 17 patients who had major vascular involvement (portal-vein/superior-mesenteric-vein) and underwent a vascular resection/repair (Group-II) during the CR. Demographics, operative and follow-up data were reviewed. RESULT: Type of the operations were: standard Whipple (n=53), pylorus-sparing-Whipple (n=41), total pancreatectomy (n=11), and distal pancreatectomy (n=13). In Group-II, venous involvement was excised and primarily repaired (n=12), or repaired using other veins (n=4) or a synthetic patch (n=1). Group-II had a significantly larger tumor size and more perineural invasion and peripancreatic soft tissue involvement (P<0.05). While complication rate, margin status, and duration of stay were not different between the groups, the median-overall-survival was higher for Group-I (15.34 months) than Group-II patients (7.18 months) (P=0.003). CONCLUSION: Pancreatic CR requiring intra-operative venous resection/repair is feasible and safe, but the survival of the patients who have pancreatic adenocarcinoma with venous involvement is poor irrespective of a successful venous resection.

Peripancreatic soft tissue involvement: independent outcome predictor in patients with resected pancreatic adenocarcinoma.

The impact of cancer involving the peripancreatic soft tissue (PST), irrespective of margin status, following a resection of pancreatic adenocarcinoma is not known. The purpose of this study is to determine such an impact on a cohort of patients. Data from 274 patients who underwent pancreatic surgery by our team between 1998 and 2012 was reviewed. Of those 119 patients who had pancreatic resection for adenocarcinoma were retrospectively analyzed. Patients were categorized into 3 groups: Group 1 = R1 resection (N = 39), Group 2 = R0 with involved PST (N = 54), and Group 3 = R0 with uninvolved PST (N = 26). Demographics, operative data, tumor characteristics and overall survival (OS) were evaluated. Operations performed were: Whipple (N = 53), pylorus sparing Whipple (N = 41), total pancreatectomy (N = 11), and other (N = 14). Median OS for Groups 1, 2, and 3 were 8.5 months, 12 months, and 69.6 months respectively (P < 0.001). Tumor size (P = 0.016), margin status (P = 0.006), grade (P = 0.001), stage (P = 0.037), PST status (P < 0.001), complications (P = 0.046), transfusion history (P = 0.003) were all predictors of survival. Cox regression analysis demonstrated that grade (HR = 3.1), PST involvement (HR = 2.7), transfusion requirement (HR = 2.6) and margin status (HR = 2.0) were the only independent predictors of mortality. PST is a novel predictor of poor outcome for patients with resected pancreatic cancer.

Genotype-phenotype correlations in recessive RYR1-related myopathies.

BACKGROUND: RYR1 mutations are typically associated with core myopathies and are the most common overall cause of congenital myopathy. Dominant mutations are most often associated with central core disease and malignant hyperthermia, and genotype-phenotype patterns have emerged from the study of these mutations that have contributed to the understanding of disease pathogenesis. The recent availability of genetic testing for the entire RYR1 coding sequence has led to a dramatic expansion in the identification of recessive mutations in core myopathies and other congenital myopathies. To date, no clear patterns have been identified in these recessive mutations, though no systematic examination has yet been performed. METHODS: In this study, we investigated genotype-phenotype correlations in a large combined cohort of unpublished (n = 14) and previously reported (n = 92) recessive RYR1 cases. RESULTS: Overall examination of this cohort revealed nearly 50% of cases to be non-core myopathy related. Our most significant finding was that hypomorphic mutations (mutations expected to diminish RyR1 expression) were enriched in patients with severe clinical phenotypes. We also determined that hypomorphic mutations were more likely to be encountered in non-central core myopathies. With analysis of the location of non-hypomorphic mutations, we found that missense mutations were generally enriched in the MH/CCD hotspots and specifically enriched in the selectivity filter of the channel pore. CONCLUSIONS: These results support a hypothesis that loss of protein function is a key predictive disease parameter. In addition, they suggest that decreased RyR1 expression may dictate non-core related pathology though, data on protein expression was limited and should be confirmed in a larger cohort. Lastly, the results implicate abnormal ion conductance through the channel pore in the pathogenesis in recessive core myopathies. Overall, our findings represent a comprehensive analysis of genotype-phenotype associations in recessive RYR1-myopathies.

Acinar cell carcinoma presenting as a duodenal mass: review of the literature and a case report.

Heterotopic pancreatic tissue is not uncommon. Although the cancerous transformation of heterotopic pancreatic tissue is a theoretical possibility, it is an extremely rare phenomenon. The majority of the heterotopic pancreatic malignancies reported in the literature are adenocarcinomas (32 cases). An Acinar Cell Carcinoma (ACC) arising from heterotopic pancreatic tissue is even less common with only six cases being reported. This report presents an extremely rare case of heterotopic pancreatic ACC presenting as a duodenal mass. We propose that heterotopic pancreatic ACC should be considered as a possibility in the differential diagnosis of a duodenal mass.

Pilot study of a hierarchical Bayes method for utility estimation in a choice-based conjoint analysis of prescription benefit plans including medication therapy management services.

BACKGROUND: Consumers face an array of multiattribute prescription benefit insurance programs that include different access points (retail, supermarket, Internet, etc) and levels of pharmacist interaction (including medication therapy management services [MTMSs]). Because of this, there is a need for more sophisticated information to drive prescription benefit plan design. OBJECTIVES: A pilot study to determine if choice-based conjoint (CBC) analysis with hierarchical Bayes (HB) estimation for individual level part-worths could provide a stable model for attribute preferences for prescription benefit insurance; to pilot test the addition of MTMSs to a prescription benefit management model; and to pilot and compare logit-based utility estimates to HB estimations in a conjoint market simulator. METHODS: A mail-based survey was conducted using a random sample of 1500 residents of the United States. A CBC analysis instrument was developed to provide a single-stated choice from a selection of different prescription benefit plans. Choice tasks were varied based on the attributes: co-payment, pharmacy access, formulary, level of pharmacist interaction including MTMSs and monthly premium. Analysis included logit-based and HB estimation for utilities, and preference share market simulation testing. RESULTS: The utility estimations from HB analysis were consistent with those seen in the logit-based analysis. A goodness of fit of 83% (root likelihood) was achieved in the HB utility estimations with only 4 choice tasks per respondents and the inclusion of MTM-like services. There was convergence on preference shares from the market simulation between the 2 estimation methods. CONCLUSIONS: The use of CBC analysis with HB estimation provided utilities similar to those estimated using aggregated logit-based methods, with the added benefit of respondent specific part-worth scores for each attribute level. A larger sample, changes in the instrument design, more panels (tasks) per respondent, and selection of conjoint methods may allow for more predictive information from market simulators.