Minimal Hepatic Encephalopathy.

Minimal hepatic encephalopathy, previously called subclinical hepatic encephalopathy, represents the earliest and mildest form of hepatic encephalopathy. It is the most under-recognized and underdiagnosed form of hepatic encephalopathy. Although there is no diagnostic gold standard, validated testing modalities have been devised to detect this neurocognitive complication. The newest developments include medically related apps for smartphones or tablets that can be easily used to diagnose and monitor minimal hepatic encephalopathy. Although recognition of this neurocognitive impairment can be challenging, early detection is paramount with the discovery of an association with worse clinical outcomes in patients diagnosed with minimal hepatic encephalopathy.

Social Impact of Hepatic Encephalopathy.

Hepatic encephalopathy (HE) is a multifaceted disorder, with effects stretching far beyond office visits and hospitalizations. Patients with HE suffer from varying degrees of altered consciousness, intellectual disability, and personality changes. A large social impact exists for patients with HE. Quality of life and activities of daily living, such as work capacity, driving ability, and sleep quality, have been shown to be affected. Additionally, caregiver and financial burdens are highly prevalent. Multiple tools exist to assess quality of life, including the CLD-Q questionnaire. Common treatments for HE, including rifaximin and lactulose, have been shown to improve overall quality of life.

Adenocarcinoma of the appendix occurring in a patient treated with paclitaxel for locally advanced esophageal cancer.

Paclitaxel has been linked with a number of immunosuppressive effects such as decreased numbers and activity of dendritic cells, NK-cells and monocytes, which may in turn lead to defective T-cell activation. In addition, this agent was shown to cause mitotic arrest resembling high-grade dysplasia throughout the gastrointestinal tract, including the appendix. We have previously documented a series of lung cancer patients who developed pre-malignant colonic polyps and/or colon cancer either during or weeks following chemotherapy with paclitaxel, suggesting a potential role of this agent in their pathogenesis. We describe herein a patient who developed adenocarcinoma of the appendix five months after paclitaxel therapy for a locally advanced lower esophageal cancer. Although the cancer of the appendix was in early stage, it was poorly differentiated and showed lymphovascular invasion. The context, timeline and existing experience suggest that this second cancer was triggered by a pre-existing insult, conceivably delivered by paclitaxel.

Accelerated Premalignant Polyposis and Second Colon Cancers: Incriminating Immunosuppression, Radiotherapy, and Systemic Chemotherapy Agents.

BACKGROUND: Cancer survivors are known to be at increased risk for second primary cancers. In addition, immunosuppression and previous cancer treatments such as radiotherapy and systemic chemotherapy are linked with increased risk of both colonic adenomas and adenocarcinomas. AIM: We performed a systematic review searching for manuscripts discussing second colon cancers, accelerated polyposis, immunosuppression, radiation, and chemotherapy. We sought to identify a link between immunosuppression and increased risks specific to premalignant polyposis and second colon cancers. FINDINGS: We identified multiple studies demonstrating associations between radiotherapy, systemic chemotherapy, and immunosuppression with a higher propensity for second colon adenomas and adenocarcinomas. When compared to the general population, these risks were more profound and the rate at which these second malignancies developed was significantly increased. CONCLUSIONS: We believe that timing for colonoscopic surveillance in these patients should be different from the general population in order to identify promptly these rapidly progressive neoplasms. Screening for second malignancies should be considered early after remission of the primary cancer is documented, especially when a prolonged survival or a cure is anticipated. We also recommend consideration be given to increasing the frequency of colonoscopy in these cohorts. Future studies are required in order to establish the optimal time interval for surveillance colonoscopy in these high-risk individuals.

Helicobacter pylori treatment: Still a work in progress.

Helicobacter pylori is a common worldwide bacterium, possessing adaptability that has created difficulty achieving eradication. While the standard treatment was thought to be triple therapy with a proton pump inhibitor, amoxicillin, and clarithromycin, growing rates of treatment failure and antibiotic resistance have stimulated research into novel regimens. Quadruple therapy with bismuth has been compared for both first- and second-line treatments, but eradication still has not reached expected goals. Innovative regimens including sequential and concomitant therapy, as well as the introduction of new antibiotics into previous treatment schedules, have shown promising improvements in eradication rates. We discuss and compare these unique regimens, reviewing the current literature to deduce those which are most likely to provide the highest success in curing H. pylori infection.

Synchronous gastric and ampullary adenocarcinomas in a hairy cell leukemia patient treated with pentostatin eight years prior.

Hairy cell leukemia patients are at increased risk for second malignancies, including both solid and lymphoid neoplasms. Along with other factors, multiple immune defects present in hairy cell leukemia likely contribute to subsequent carcinogenesis. We report herein a case of synchronous high-grade gastric and ampullary adenocarcinomas in a patient with a history of hairy cell leukemia treated eight years prior with pentostatin. We include a review of immune alterations induced by both hairy cell leukemia and its therapies, and link them with the occurrence of second cancers in these patients.

Adenocarcinoma of the ampulla of Vater: what treatment options are available?

The scientific literature on adenocarcinoma of the ampulla (papilla) of Vater suggests that it either represents a distinct entity or is more closely related to small bowel adenocarcinoma than to the biliary malignancies. The ambiguity surrounding this rare cancer has kindled research exploring its immunohistochemistry aspects and gene expression profiling. While the basis of management for resectable disease remains surgical intervention, the role of adjuvant chemotherapy is not clear. A recent large phase 3 clinical trial conducted in patients with resected ampulla of Vater adenocarcinoma favored adjuvant chemotherapy over observation alone. The standards of therapy for the advanced small bowel adenocarcinoma and biliary cancer are fluoropyrimidine derivatives and gemcitabine-based combinations, respectively. In addition, new biologic and targeted agents may enhance clinical results seen in this cancer type. Therefore, diligently designed clinical trials are necessary to establish its optimal treatment strategies. We describe herein a patient with ampulla of Vater adenocarcinoma who had an exceptional response to fluoropyrimidine-based chemotherapy. We further include a discussion reviewing the clinicopathologic aspects of this neoplasm as well as focus on currently available and future therapeutic options.

What are the latest pharmacotherapy options for small bowel adenocarcinoma?

Incidence of small bowel adenocarcinoma is slowly but steadily increasing. As we gain more knowledge of the molecular basis of this disease, we may be able to approach it via using novel biologic or targeted therapies with or without traditional chemotherapy agents. In the meantime, early diagnosis is still best as it prompts early surgical resection and offers potential cure. The role of adjuvant and neoadjuvant therapy is currently being explored in clinical trials. Several clinical trials have suggested that first-line chemotherapy for patients with metastatic disease should consist of either 5-fluorouracil-leucovorin-oxalipatin or capecitabine-oxaliplatin, while 5-fluorouracil-leucovorin-irinotecan can be reserved for second-line treatment. However, we realize the limitations of these studies, given their small sample size and/or retrospective nature. Single-agent 5-fluorouracil/capecitabine should be considered in patients who are either intolerant to or experience significant side effects with oxaliplatin or irinotecan. We believe that cancers originating in the ampulla of Vater probably deserve a prospective randomized trial of cisplatin-gemcitabine, the current standard of therapy for advanced biliary malignancies.