Tests, labs: The workup of such patients should include testing for serum ANA, ASMA, anti-LKM, serum protein electrophoresis (SPEP), and quantitative immunoglobulins (SIEP). Urgent liver biopsy, transjugular if appropriate, may help to confirm the clinical suspicion of acute autoimmune hepatitis. Rapid institution of treatment with high-dose corticosteroids may rescue patients whose disease ultimately would have progressed to either fulminant hepatic failure or cirrhosis. Other patients continue to deteriorate in spite of immunosuppressant therapy. Accordingly, a low threshold should exist for transferring patients with acute liver failure to tertiary care hospitals that are capable of performing emergent liver transplantation.
Common sx: Fatigue Upper abdominal discomfort Mild pruritus Anorexia Myalgia Diarrhea Cushingoid features Arthralgias Skin rashes (including acne) Edema Hirsutism Amenorrhea Chest pain from pleuritis Weight loss and intense pruritus (unusual)
Without therapy, most patients die within 10 years of disease onset.
16 Treatment with corticosteroids has been shown to improve the chances for survival significantly. Indeed, the life expectancy of patients in clinical remission is similar to that of the general population. Many patients have histologic evidence of cirrhosis at the onset of symptoms. This is true both for patients with an initial presentation of acute hepatitis and for patients with chronic hepatitis. Thus, subclinical disease often precedes the onset of symptoms. As many as 20% of patients present initially with signs of decompensated cirrhosis. In other patients, chronic hepatitis progresses to cirrhosis after years of unsuccessful immunosuppressant therapy marked by multiple disease relapses. This is said to occur in 20-40% of patients. Patients with cirrhosis may experience classic symptoms of portal hypertension, namely variceal bleeding, ascites, and hepatic encephalopathy. Patients with complications of cirrhosis should be referred for consideration of liver transplantation.Disease associations: Autoimmune hepatitis, especially type 2, is associated with a wide variety of other disorders. Involvement of other systems may present at disease onset or may develop during the course of active liver disease. These conditions, most of which are immunologic in origin, include the following: Hematologic complications Hematologic manifestations of hypersplenism Autoimmune hemolytic anemia Coombs-positive hemolytic anemia Pernicious anemia Idiopathic thrombocytopenic purpura Eosinophilia Gastrointestinal complications Inflammatory bowel disease (6%): The presence of ulcerative colitis in patients with autoimmune hepatitis should prompt performance of cholangiography to exclude PSC. Celiac disease: One recent study of 140 pediatric patients with autoimmune hepatitis, autoimmune cholangitis, and overlap syndrome identified 23 patients with celiac disease.17 Proliferative glomerulonephritis Fibrosing alveolitis Pericarditis and myocarditis Endocrinologic complications Graves disease (6%) and autoimmune thyroiditis (12%) Juvenile diabetes mellitus Rheumatologic complications Rheumatoid arthritis and Felty syndrome Sjögren syndrome Systemic sclerosis Mixed connective-tissue disease Erythema nodosum Leukocytoclastic vasculitis: Patients may present with symptoms of leg ulcers. Febrile panniculitis Lichen planus Uveitis The hepatitis C connection The hepatitis C virus (HCV) has several important associations with autoimmune hepatitis. The prevalence rate of HCV infection in patients with autoimmune hepatitis is similar to that in the general population. This implies that HCV is not an important factor in the etiology of autoimmune hepatitis; however, patients who are seropositive for anti–LKM-1 frequently are infected with HCV. These patients have predominant features of chronic viral hepatitis and frequently lack antibodies to P-450 IID6. Such patients respond to treatment with interferon. They should be distinguished from anti–LKM-1-positive patients who have a positive anti–P-450 IID6, are seronegative for anti-HCV, and are responsive to steroid therapy.18 False-positive results on anti-HCV enzyme-linked immunoassay (ELISA) tests are described in the setting of hypergammaglobulinemia, including that observed in patients with autoimmune hepatitis. In patients with ANA and/or ASMA seropositivity and a positive anti-HCV, a false-positive reaction to HCV should be excluded by performing a test for HCV RNA using the polymerase chain reaction (PCR). In general, patients with definite autoimmune hepatitis have median serum titers of ASMA and ANA of 1:160 and 1:320, respectively. In contrast, these titers may be in the range of 1:80 or less in patients with true chronic viral hepatitis. Although autoimmune hepatitis and chronic HCV have similar histologic features, moderate-to-severe plasma cell infiltration of the portal tracts is more common in patients with autoimmune hepatitis. Portal lymphoid aggregates, steatosis, and bile duct damage are more common in patients with chronic HCV. Overlap syndromes: Patients with autoimmune hepatitis may present with features that overlap those classically associated with patients with PBC and PSC. About 7% of patients with autoimmune hepatitis have a disease that overlaps with PBC. They may have a detectable AMA (usually in low titer), histologic findings of bile duct injury and/or destruction, and the presence of hepatic copper. The natural history of the disease tends to echo type 1 autoimmune hepatitis. Patients with the autoimmune hepatitis-PBC overlap syndrome may improve with steroid therapy. Recently, one group of authors compared the progression of hepatic fibrosis in patients with autoimmune hepatitis-PBC treated with ursodiol monotherapy with patients treated with ursodiol in combination with immunosuppressants.19 The mean duration of follow-up was 7.5 years. In noncirrhotic patients, fibrosis progression was seen in 4 of 8 patients treated with ursodiol monotherapy, as compared to 0 of 6 patients treated with combination therapy (P = 0.04). Thus, treatment combining ursodiol and immunosuppressants may be advisable in patients with the autoimmune hepatitis-PBC overlap syndrome. About 6% of patients with autoimmune hepatitis have a disease that overlaps with PSC. Patients with the autoimmune hepatitis-PSC overlap syndrome frequently have concurrent inflammatory bowel disease. The liver biopsy findings reveal bile duct injury. Findings from cholangiograms are abnormal. Such patients usually have mixed hepatocellular and cholestatic liver chemistries and typically are resistant to steroid therapy. Treatment with ursodiol should be considered. The natural history of autoimmune hepatitis-PSC is not well studied. One recent article assessed 41 consecutive patients with PSC, 34 patients with classical PSC and 7 patients with the autoimmune hepatitis-PSC overlap syndrome.20 The mean follow-up period was 14 years. Patients with autoimmune hepatitis-PSC tended to present at a younger age and had more elevated aminotransferases and serum IgG measurements than patients with classical PSC. They also appeared to have a better chance for transplant-free survival. One case of cholangiocarcinoma, no deaths, and 1 transplant were reported among the 7 patients with autoimmune hepatitis-PSC, as compared to 5 cases of cholangiocarcinoma, 9 deaths, and 6 transplants among the 34 patients with classical PSC. Autoimmune cholangitis is characterized by mixed hepatic and cholestatic liver chemistries, positive ANA and/or ASMA, negative AMA, antibodies to carbonic anhydrase, and histology that resembles PBC. Some authors contend that this condition is AMA-negative PBC. Patients may have an unpredictable response to therapy with steroids or ursodiol. Cryptogenic autoimmune hepatitis is characterized by a clinical picture that is indistinguishable from autoimmune hepatitis. Here, the diagnosis is made by liver biopsy. ANA, ASMA, and anti–LKM-1 are negative at disease onset and may appear late in the disease course, as might anti-SLA. The disease usually is responsive to steroid therapy. Treatment of AIH: http://emedicine.medscape.com/article/172356-treatment Autoimmune Pancreatitis Sx of: 1. abdominal pain (65%), jaundice (62%), weight loss (42%). Pancreatic mass, elargement or prominence (85%). Serum IgG4 elevated (44%); The most common extrahepatic finding was biliary strictures (35%). Peripancereatic vascular complications can occur in 23% pts. Rx: Steroid dependant; sometimes imuran and steroids B------------------------------------- B Barrett's: Diagnosis, Surveillance and Therapy of Barrett’s Esophagus (March 2008, ACG) How to Manage a Barrett’s Esophagus Patient With Low-Grade Dysplasia: http://www.usagiedu.com/articles/lgdbe/lgdbe.pdf Excellent review of all therapies including RFA, EMR: http://www.sciencedirect.com/science?_ob=ArticleRL&_udi=B7CRK-4V889M9-1&_user=10&_coverDate=01%2F31%2F2009&_rdoc=1&_fmt=high&_orig=browse&_srch=doc-info(%23toc%2317997%232009%23999839996%23796107%23FLA%23display%23Volume)&_cdi=17997&_sort=d&_docanchor=&view=c&_ct=1&_acct=C000050221&_version=1&_urlVersion=0&_userid=10&md5=7f31f4634e6bc5db051b2a70b4d71772
2009 Jan;41(1):2-8. Epub 2009 Jan 21. Stepwise radiofrequency ablation of Barrett's esophagus preserves esophageal inner diameter, compliance, and motility: http://www.ncbi.nlm.nih.gov/pubmed/19160152 RFA of Barrett's: http://www.mayoclinic.org/news2006-jax/3244.html http://www.medicalnewstoday.com/articles/151637.php C------------------------------------- CCholangiocarcinoma
http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=cmed&part=A24039 Cholangitis Needle-knife precut sphincterotomy Endoscopic biliary drainage for severe acute cholangitis. The sphincterotomy is iniciates with pre-cut needle emerging abundant purulent secretion (Colangitis). Charcot triad of fever, RUQ pain, and jaundice is found in 50-70% of patients presenting with cholangitis. Fever is present in approximately 90% of cases. Abdominal pain and jaundice is thought to occur in 70% and 60% of patients, respectively. Patients present with altered mental status 10-20% of the time and hypotension approximately 30% of the time. These signs combined with Charcot triad constitute Reynolds pentad. Most patients complain of RUQ pain; however, some patients (ie, elderly persons) are too ill to localize the source of infection. Other symptoms include the following: Jaundice Fever, chills, and rigors Pruritus Acholic or hypocholic stools The patient's past medical history may be helpful. For example, a history of the following increases the risk of cholangitis: Gallstones, CBD stones Recent cholecystectomy Endoscopic manipulation or ERCP, cholangiogram History of cholangitis History of HIV or AIDS: AIDS-related cholangitis is characterized by extrahepatic biliary edema, ulceration, and obstruction. Etiology is uncertain but may be related to cytomegalovirus or cryptosporidium infections. Manage cholangitis as described below, although decompression usually is not necessary. Choledochocele http://www.ikp.unibe.ch/lab2/CHOLCELE.html The web site for: Adult Pancreaticobiliary Tract and Pancreas: Part 1 includes classification of choledochoceles Cirrhosis Risk Factors for Morbidiy and Mortality in Patients with Cirrhosis Undergoing Surgery: http://www.ncbi.nlm.nih.gov/pubmed/17408652 ;Higher risk of surgery with these types of surgeries: Abdomial, cardiac, emergency, hepatic resection; Higher risk of surgery with thes types of patient characteristics: anemia, ascites, child's class (C>B), encephalopathy, hypoalbuminemia, hypoxemia, infection, jaundice, malnutrition, portal htn, prolonged PT>2.5 that does not correct with vitamin K Child's Pugh score: http://homepage.mac.com/sholland/contrivances/childpugh.html MELD score: http://www.mayoclinic.org/meld/mayomodel7.html Follow up in patients with cirrhosis: 1. varices: http://www.jhep-elsevier.com/article/PIIS0168827803000114/fulltext 2. Beta-blocker: propranolol or nadalol 3. Encephalopathy Rx 4. Hepatocellular CA: check alpha-fetoprotein, CT hepatoma protocol 5. Ascites? Need SBP prophylaxis? Collagenous Colitis Information: http://www.orpha.net/data/patho/GB/uk-CC.html \\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\ Colon Cancer syndromes: HNPCC: Gastroenterology News http://gastroendonews.com/ (em/sp) Colon Cancer Colorectal Cancer Screening (March 2009)Diagnosis, Treatment and Surveillance for Patients with Colorectal Polyps (November 2000) 6% chance of getting colon cancer overall; Increased risk of colon cancer: +FHx, IBD, DM, Obesity, red meat consumption, Etoh, TOB;Decreased risk of colon cancer: exercise, Ca/vit D, ASA, postmenapausal estrogen, Folic acid (?) Hepatic metastasis with CRC is common, owing to intestinal venous outflow by way of the portal system, and will occur in roughly one-third of patients. Among other factors, more than 3 hepatic metastases in total serve as a predictor of poor survival ([cite/4253[/cite]). If lesions in are limited to 2, and they are metachronous (i.e., nonconcurrent) relative to the resected primary, this is a favorable sign. However, if both of the nodules are sizeable, and/or they are situated near critical structures, so that immediate surgical access could prove difficult. Or if intestinal obstruction and lymphatic involvement (4416) , his recurrent disease is not unexpected. Clinicopathologic features imparting greater risk of tumor recurrence include (4255): Poorly differentiated malignancies Lymphatic/blood vascular and/or perineural invasion T4 tumor stage Intestinal obstruction or perforation Preoperative carcinoembryonic antigen elevation (plasma) At this juncture, Jim's treatment options remain sufficiently broad, despite his comorbidities (diabetes, hypertension, and hyperlipidemia). Even with diabetic neuropathy, the FOLFOX he received as earlier adjuvant therapy is not excluded; and while bevacizumab has certain toxicities (hypertension, cardiovascular events, etc), which are often more troublesome for the elderly, it is not necessarily an inappropriate agent for Jim. In practice, age or existing hypertension rarely precludes bevacizumab use.Clinical studies alternatively have suggested that the anti-EGFR monoclonal antibody, cetuximab, is safe and effective when combined with either an oxaliplatin- or irinotecan-based regimen as first-line treatment of metastatic CRC (mCRC). The phase III CRYSTAL study supports the use of the FOLFIRI (5-FU/leucovorin/irinotecan) regimen plus cetuximab as neoadjuvant therapy for potentially curative R0 hepatic resection (4260, 4299). Bokemeyer and associates also recently published data from the OPUS trial on the use of FOLFOX-4 (N=233), with and without cetuximab, in first-line treatment of mCRC. Patients with KRAS wild-type tumors had a better chance of therapeutic response (ORR=61% vs 37%; odds ratio=2.54; P=.011) and a reduced risk of disease progression (hazard ratio=0.57; P=.0163) with addition of cetuximab, compared with FOLFOX-4 alone (4299).Given that Jim's tumor is genotypically KRAS wild-type, added cetuximab might well enhance medical treatment intended to shrink his borderline-resectable metastases and facilitate surgical excision. Indeed, some patients may opt for immediate surgical resection, without prior medical intervention. Assuming treatment is in order, however, Jim should undergo surgical reassessment within 8-10 weeks of starting treatment (4409). His choices of therapy include: FOLFIRI plus bevacizumab or cetuximab FOLFOX plus bevacizumab or cetuximab FOLFOXIRI FOLFOX FOLFIRIAn important consideration is that bevacizumab must be discontinued at least 6 weeks before surgery in order to avoid wound healing complications. This is not a requirement of cetuximab and thus bolsters the rationale for its use, although cetuximab is not yet FDA-sanctioned specifically for first-line therapy. NCCN Guidelines stipulate that resection should be performed as soon as possible after a patient becomes eligible, and ideally no more than 3-4 months from initiating preoperative therapy (4409). Beyond this limit, the risk for liver toxicity increases, and the ability to successfully withstand surgery is diminished. A recently reported study by Zorzi and colleagues identified 9 or more cycles of chemotherapy (FOLFOX with or without bevacizumab) as the sole independent factor predictive of postoperative liver insufficiency (P=0.031; odds ratio=3.90) in liver-limited CRC patients (N=219) undergoing resection (4322).When isolated liver metastases occur with CRC, tumor resection affords the only opportunity for cure, eventuating in 5-year survival rates of 25%-40%. Nonetheless, up to 85% of Stage IV CRC patients do not initially qualify for resection. It is only through neoadjuvant therapy, as illustrated, that the percentage of surgically-eligible patients is expanded. The resultant shift in survival rates surely calls for a revision of current CRC staging, in order to differentiate this growing curative subset from otherwise palliative patients and reflect the dramatic achievements of recent therapeutic advances (4258. cites['Cite4255'] = '4255Wolpin BM, Meyerhardt JA, Mamon HJ, Mayer RJ. Adjuvant treatment of colorectal cancer. CA Cancer J Clin. 2007 May-Jun;57(3):168-85. Review. PMID: 17507442'; cites['Cite4258'] = '4258Poston GJ, Figueras J, Giuliante F, et al. Urgent need for a new staging system in advanced colorectal cancer. J Clin Oncol. 2008 Oct 10;26(29):4828-33. Epub 2008 Aug 18. PMID: 18711170'; cites['Cite4260'] = '4260Lee JJ, Chu E. First-line use of anti-epidermal growth factor receptor monoclonal antibodies in metastatic colorectal cancer. Clin Colorectal Cancer. 2007 Oct;6 Suppl 2:S42-6. Review. PMID: 18021486'; cites['Cite4299'] = '4299Bokemeyer C, Bondarenko I, Makhson A, et al. Fluorouracil, Leucovorin, and Oxaliplatin With and Without Cetuximab in the First-Line Treatment of Metastatic Colorectal Cancer. J Clin Oncol. 2008 Dec 29. [Epub ahead of print]. PMID: 19114683'; cites['Cite4322'] = '4322Zorzi D, Kishi Y, Maru DM, et al. Effect of extended preoperative chemotherapy on pathologic response and postoperative liver insufficiency after hepatic resection for colorectal liver metastases. 2009 American Society of Clinical Oncology Gastrointestinal Cancers Symposium. San Francisco, CA. Abstract 295.'; cites['Cite4409'] = '4409National Comprehensive Cancer Network. Colon Cancer. Clinical Practice Guidelines in Oncology V.2.2008. Available at: http://www.nccn.org. Accessed: February, 2009.'; cites['Cite4416'] = '4416Lin JI, Cogbill CL, Athota PJ, et al. Superficial spreading adenocarcinoma of appendix, cecum, and terminal ileum. Dis Colon & Rectum 1980;23(8):587-589.'; rules['7663'] = ' Advanced CRC TreatmentMore than half of the patients who develop CRC will either present with or progress to advanced disease (4337). Although there are no fixed strategies for first-line chemotherapy or beyond, this is currently an area of great enthusiasm and optimism (4348).First-LineHaving established the first-line equivalency of FOLFOX and FOLFIRI through a French study (4364) (response rates: FOLFOX6, 54%; FOLFIRI, 56%) and an Italian trial by Colucci and colleagues (4341) (response rates: FOLFOX4, 36%; FOLFIRI, 34%), the current therapeutic goal is to optimize these regimens and manage toxicities through various delivery strategies, such as staging and stop-and-go (4349). Either one of the above is therefore acceptable as first-line therapy, although 3-drug FOLFOXIRI (folinic acid, infusional FU, oxaliplatin, and irinotecan) has also prolonged patient survival (4346), and a number of studies support bevacizumab combined with a doublet regimen (FOLFOX, CAPEOX, FOLFIRI) or simply FU/leucovorin as an appropriate first-line option (4339, 4254). Bevacizumab is currently FDA-approved for combination use with a 5FU-based regimen as first- or second-line therapy of mCRC (4355).Second-Line and BeyondThe choice of second-line therapy relies largely on selection and outcome of first-line treatment. In this regard, sequential administration of FOLFOX and FOLFIRI are addressed later (See Sequencing of Regimens). However, based on a trial by Giantonio and colleagues, which evaluated FOLFOX plus bevacizumab in patients with IFL-refractory metastatic CRC, the addition of this agent to second-line therapy of bevacizumab-naïve patients is valid (4347). Alternatively, a combination regimen with added cetuximab is a consideration for K-RAS wild-type tumors.Patients refractory to first- and second-line multi-drug treatments ultimately have few standard options. Cetuximab is approved for second- and subsequent-line use with metastatic, K-RAS wild-type disease unresponsive to irinotecan (4356). The BOND-2 study, in which such patients were randomly assigned to salvage therapy of either bevacizumab and cetuximab in tandem or bevacizumab and cetuximab plus irinotecan, produced a 37% response rate with the 3-drug combination (4362). Although there were no unusual side effects from these biologic agents when used together, the PACCE and CAIRO2 studies have subsequently shown that dual antibodies (bevacizumab plus an anti-EGFR mAB) in first-line therapy actually confer inferior outcomes (4352, 4358).Panitumumab is specifically indicated as single-agent therapy of metastatic CRC refractory to prior or ongoing FU-, oxaliplatin-, and irinotecan- based regimens. Its dermatologic side effects, however, are severe and affect a majority (89%) of treated patients on monotherapy. The successful trial upon which FDA approval of panitumumab hinged yielded an impressive 46% drop in the rate of tumor progression when used alone for qualified patients versus best supportive care (P 4333, 4336, 4357).NeoadjuvantResection/ablation of metastases confined to the liver, can be curative in about 35% of eligible patients (4348). For those who are otherwise unresectable, preoperative therapy may enable downsizing, providing hope for eventual disease control or cure through metastasectomy. Oxaliplatin-based therapy, interestingly, has trended towards a higher rate of hepatic resectability. One particular investigation by Tournigand and colleagues cites a higher rate of metastatectomy for first-line FOLFOX (13%) compared with FOLFIRI (7%). It is the degree of neoadjuvant efficacy in patients with liver-only disease that strongly influences surgical feasibility (4364). A recent study by Nordlinger, et al. (EORTC Intergroup trial 40983), comparing perioperative FOLFOX4 with surgery alone for resectable liver metastases, demonstrated a siignificant benefit inprogression-free survival for patients receiving perioperative chemotherapy (4278).'; Literature Review Colorectal cancer (CRC) ranks third in the United States among cancers of both men and women, with close to 150,000 cases diagnosed annually. While it also sadly represents the second leading cause of cancer-related death, there is new reason for hope. The death rate has been declining for the past 20 years, due in part to better screening, but also thanks to a surge in therapeutic options from the past decade. There are now nearly one million CRC survivors within this country (4334). This recent progress reflects the introduction of novel drugs and innovative strategies, including adjuvant therapy for localized, high-risk cancers, a multimodal stance for advanced or metastatic disease, and specific enhancements in surgical techniques. A distinct improvement in 5-year overall CRC survival rates (from 50% to 63%) and a doubling of the median overall survival time for advanced CRC have been the result. Today’s methods far eclipse the longtime historical standard of systemic fluorouracil (FU) monotherapy which, despite all attempts to maximize efficacy, peaked at a mere 10% to 20% tumor response rate (4348). Cytotoxic AgentsIrinotecan, capecitabine, and oxaliplatin represent the newer cytotoxic drugs for CRC, first approved by the US Food and Drug Administration (FDA) in 1996, 1998 and 2002, respectively. Their mechanisms of action affect impartially both normal and malignant cells. Irinotecan is an inhibitor of topoisomerase I, a required enzyme for DNA replication and cell division. The oral fluoropyrimidine, capecitabine, undergoes a 3-step enzymatic conversion systemically to yield the biologic equivalent of infusional 5-FU. Oxaliplatin is a water-soluble, platinum-based compound superior to cisplatin in its ability to directly interfere with DNA replication (4366, 4367). FDA-approved Biologic AgentsThe latest additions to the CRC treatment arsenal, the biologic (targeted) agents, are fundamentally different from their cytotoxic predecessors. They include several target-specific monoclonal antibodies (mAbs) that disrupt the dysregulated cellular pathways responsible for tumor growth and secondary angiogenesis. Their benefits have been shown for a variety of solid malignancies, and they hold particular promise in the setting of advanced CRC, acting in synergy with conventional chemotherapy (4336, 4339). BevacizumabBevacizumab is a humanized mAb (97% human; 7% murine-derived) selective for vascular endothelial growth factor (VEGF). VEGF is elevated in up to 50% of colorectal malignancies and when overexpressed, can be a determinant of poor prognosis. In preclinical studies, the effects of combination chemotherapy were enhanced by bevacizumab, presumably via vascular stabilization and improved circulatory access to drugs. Its single-agent activity with CRC is minimal (4331, 4339). CetuximabCetuximab is a recombinant murine-human chimeric mAb directed at the extracellular domain of epidermal growth factor receptor (EGFR). Key pathways for cell growth, division, and survival are interrupted by cetuximab, as are messaging streams vital for tumor metastasis and angiogenesis. Cetuximab also potentiates the effects of irradiation and cytotoxic drugs and is best used with other agents, although it does possess single-agent activity (4331, 4336, 4339, 4340). PanitumumabPanitumumab is a fully humanized mAb to the extracellular domain of EGFR. In preclinical studies, panitumumab displayed antitumor and chemopotentiating effects similar to those of cetuximab. FDA approval was granted in late 2006, based on a phase III trial where recipients showed improved progression-free survival after failing standard chemotherapy (4333, 4339). One singular advantage of the mAbs is their generally long half-lives (4331). This translates into less frequent dosing relative to standard chemotherapy, but there are caveats. For example, patient response to cetuximab early-on had inexplicably failed to correlate consistently with EGFR overexpression as determined by immunohistochemistry (IHC) (4339, 4360, 4365). The National Comprehensive Cancer Network hence discouraged IHC determination of EGFR expression as a requirement for its use, overriding the original FDA consensus on cetuximab (4360). Pivotal research conducted by Lièvre (4354), Amado (4332), and others (4344, 4345) has since demonstrated that K-RAS mutations are associated with resistance to both cetuximab and panitumumab, as anti-EGFR agents. RAS proteins participate in the RAS-RAF-MEK3-ERK-MAP kinase pathway involved in cellular responses to growth signals. Somatic mutations of the RAS genes, activating this pathway, are therefore common in human cancers, as well as in polyps and precursor lesions of CRC (4338). K-RAS status can be assessed retrospectively via staining of formalin-fixed, paraffin-embedded tissue with no appreciable difference in results whether primary or metastatic tumor is sampled (4351). Adjuvant TherapyOver the past 20 years, adjuvant chemotherapy for CRC has transitioned to mainstream patient care from its experimental origins. The pivotal Intergroup 0089 study of stage II and III patients showed a survival advantage with FU plus either high- or low-dose leucovorin and provided significant impetus for this shift (4350). Meta-analyses of pooled stage II and III data contributed too by revealing that modulated fluorouracil decreased the risk of death by 26% overall, and by 40% for the stage III subgroup, compared with surgery alone (4348). The subsequent addition of oxaliplatin to a 5-FU/LV backbone has now become standard after the MOSAIC and NSABP C-07 trials documented improvement in relapse rates of 24% and 21% respectively with a doublet regimen (4335, 4353). Today, a stage III recipient of FOLFOX (folinic acid, infusional FU, and oxaliplatin), given optimal resection, stands a 75% chance of remaining disease-free at 3 years, and most will be cured (4348). Several US and European trials with irinotecan plus bolus FU and leucovorin (IFL or FOLFIRI) have not matched the success of FOLFOX in the adjuvant setting. With IFL in particular, high toxic death rates were of major concern. For this reason, inclusion of irinotecan in an adjuvant regimen is not advised at this point. The American Society of Clinical Oncology similarly recommends that adjuvant treatment with stage II CRC be reserved for only those patients with evidence of high-risk disease. Sufficient benefit to offset risk has not yet been shown for this group (4348). Adjuvant treatment of rectal cancers warrants a separate discussion. Radiation is used extensively in treatment protocols for rectal cancer, whereas it is relatively ineffective for cancers of the colon. Outcomes for locally advanced rectal cancers are significantly improved by adjuvant pelvic chemoradiation versus surgery alone, and preoperative (neoadjuvant) radiation can reduce the risk of local recurrence. Irinotecan, FU or capecitabine, and oxaliplatin have all been variably used in this setting for radiosensitization, although irinotecan has as yet shown little benefit and introduces considerable GI toxicity (4348). Advanced CRC TreatmentMore than half of the patients who develop CRC will either present with or progress to advanced disease (4337). Although there are no fixed strategies for first-line chemotherapy or beyond, this is currently an area of great enthusiasm and optimism (4348). First-LineHaving established the first-line equivalency of FOLFOX and FOLFIRI through a French study (4364) (response rates: FOLFOX6, 54%; FOLFIRI, 56%) and an Italian trial by Colucci and colleagues (4341) (response rates: FOLFOX4, 36%; FOLFIRI, 34%), the current therapeutic goal is to optimize these regimens and manage toxicities through various delivery strategies, such as staging and stop-and-go (4349). Either one of the above is therefore acceptable as first-line therapy, although 3-drug FOLFOXIRI (folinic acid, infusional FU, oxaliplatin, and irinotecan) has also prolonged patient survival (4346), and a number of studies support bevacizumab combined with a doublet regimen (FOLFOX, CAPEOX, FOLFIRI) or simply FU/leucovorin as an appropriate first-line option (4339, 4254). Bevacizumab is currently FDA-approved for combination use with a 5FU-based regimen as first- or second-line therapy of mCRC (4355). Second-Line and BeyondThe choice of second-line therapy relies largely on selection and outcome of first-line treatment. In this regard, sequential administration of FOLFOX and FOLFIRI are addressed later (See Sequencing of Regimens). However, based on a trial by Giantonio and colleagues, which evaluated FOLFOX plus bevacizumab in patients with IFL-refractory metastatic CRC, the addition of this agent to second-line therapy of bevacizumab-naïve patients is valid (4347). Alternatively, a combination regimen with added cetuximab is a consideration for K-RAS wild-type tumors. Patients refractory to first- and second-line multi-drug treatments ultimately have few standard options. Cetuximab is approved for second- and subsequent-line use with metastatic, K-RAS wild-type disease unresponsive to irinotecan (4356). The BOND-2 study, in which such patients were randomly assigned to salvage therapy of either bevacizumab and cetuximab in tandem or bevacizumab and cetuximab plus irinotecan, produced a 37% response rate with the 3-drug combination (4362). Although there were no unusual side effects from these biologic agents when used together, the PACCE and CAIRO2 studies have subsequently shown that dual antibodies (bevacizumab plus an anti-EGFR mAb) in first-line therapy actually confer inferior outcomes (4352, 4358). Panitumumab is specifically indicated as single-agent therapy of metastatic CRC refractory to prior or ongoing FU-, oxaliplatin-, and irinotecan- based regimens. Its dermatologic side effects, however, are severe and affect a majority (89%) of treated patients on monotherapy. The successful trial upon which FDA approval of panitumumab hinged yielded an impressive 46% drop in the rate of tumor progression when used alone for qualified patients versus best supportive care (P < .001) (4333, 4336, 4357). NeoadjuvantResection/ablation of metastases confined to the liver, can be curative in about 35% of eligible patients (4348). For those who are otherwise unresectable, preoperative therapy may enable downsizing, providing hope for eventual disease control or cure through metastasectomy. Oxaliplatin-based therapy, interestingly, has trended towards a higher rate of hepatic resectability. One particular investigation by Tournigand and colleagues cites a higher rate of metastatectomy for first-line FOLFOX (13%) compared with FOLFIRI (7%). It is the degree of neoadjuvant efficacy in patients with liver-only disease that strongly influences surgical feasibility (4364). A recent study by Nordlinger et al. (EORTC Intergroup trial 40983), comparing perioperative FOLFOX with surgery alone for resectable liver metastases demonstrated a significant benefit in progression-free survival for patients receiving perioperative chemotherapy (4278). Other Therapeutic ParametersTiming of TherapyThe timing of any comprehensive treatment plan is critical in that delays predispose to patient deterioration (4358). One must therefore be mindful of potential drug interactions, toxicity profiles, and/or major contraindications for use when formulating complex protocols. A case in point is bevacizumab. Impaired wound healing was openly cited in its preclinical development. A 28-day postsurgical delay with evidence of satisfactory wound healing is thus essential before instituting therapy. A second and perhaps lesser recognized corollary is that this agent may similarly hamper liver regeneration. An eight-week waiting period is therefore suggested in the aftermath of bevacizumab prior to hepatic surgery (4342). Duration of TreatmentAnother practical consideration, and one that has been scarcely explored, is the duration of therapy. Its relationship to the somewhat arbitrary question of individual tolerance may offer explanation. While treatment duration is of lesser concern with fluoropyrimidine therapy, where relative toxicity is low, oxaliplatin is altogether different. In the United States, oxaliplatin-based FOLFOX is the most popular first-line drug regimen for advanced CRC, and it is also the regimen of choice for first-line therapy if bevacizumab is added. Since cumulative sensory neurotoxicity, by default, forces dosing restraints with oxaliplatin, when combined with bevacizumab to ostensibly prolong the time to progression, the issue of tolerance suddenly looms larger. It has been argued that in unlike irinotecan, where severe side effects may be lower but more often result in hospitalization, the greater risk of oxaliplatin-induced neurotoxicity can be managed on an outpatient basis. However, oxaliplatin neurotoxicity is often responsible for treatment discontinuation and may persist for months after withdrawal. Few studies to date have focused expressly on time requirements for development of neurotoxicity or have examined its impact on other therapeutic parameters (4349, 4359). Sequencing of RegimensThe choice of a first-line therapy for CRC must be tempered by the fact that over one-third (30% to 40%) of patients will be ineligible for second-line treatment. This provides a plain incentive for administering the most effective regimen up front. Treatment toxicity and patient preference or baseline medical status may also impact this decision appreciably, and realistically, the question of affordability cannot be ignored (4359). While results of the 2004 GERCOR study reported by Tournigand and colleagues showed that first-line CRC response rates for both FOLFOX6 (54%) and FOLFIRI (56%) were roughly equivalent, second-line response rates for the FOLFOX6/FOLFIRI sequence vs FOLFIRI/FOLFOX6 differed significantly (4% and 15%, respectively; P = 0.05). Regardless of this apparent performance edge for FOLFIRI and the frequency of drug-related discontinuations due to oxaliplatin, FOLFOX is a more popular first-line therapy in the US. The bias for FOLFOX may be related to its lower risks of gastrointestinal toxicity (i.e., nausea, vomiting, and diarrhea), febrile neutropenia and alopecia (4364). Another 2004 meta-analysis of seven clinical trials by Grothey and associates, further updated by addition of four large phase III studies, has contributed an alternate perspective. From this effort, it was concluded that cumulative exposure to the three active cytotoxic agents (FU/LV, irinotecan, and oxaliplatin) is central to CRC therapy, as opposed to the customary emphasis placed on a specific first-line regimen. This opinion is supported by a discovered correlation between overall patient survival and the percentage of three-drug recipients. In other words, it is the sum of drugs, and not the sequence in which they are delivered, from which patients with advanced CRC will benefit most (4349). To this end, an Italian research group, led by Falcone, released results of a phase III trial investigating use of a full three-drug combination as first-line therapy. Treatment-naïve advanced CRC patients were recruited and randomly assigned to either a regimen of FOLFIRI or FOLFIRI plus oxaliplatin (FOLFOXIRI). As expected, higher rates of severe but clinically asymptomatic neutropenia and sensory neurotoxicity were recorded for the FOLFOXIRI test group, but the study outcome was decisively in favor of the three-drug combination. Not only was the response rate for FOLFOXIRI dramatically better compared with FOLFIRI (60% vs 34%, respectively), but R0 metastasectomy was possible for a fair percentage of patients (15% with stage IV and 36% with liver-only disease) as a potentially curative measure. The latter portends a place for neoadjuvant FOLFOXIRI (4346). Extended Maintenance TherapyUpon remission, many patients may elect to continue with a maintenance therapy. A continuous program may boost overall patient compliance by eliminating any inertia to reinstitution of therapy. Then again, if disease state is stable, treatment interruption affords some relief from the rigors of chemotherapy. The decision to do so, however, is complicated by the choice of whether or not a new treatment plan or the prior regimen should be reintroduced when needed. No minimum threshold for TTP has yet been established for this purpose (4359). With respect to a maintenance rationale, the issue of treatment toxicity is key, and particularly the cumulative neurotoxicity of oxaliplatin. In the OPTIMOX1 study, 620 previously untreated patients were randomly assigned to either FOLFOX4 on a biweekly schedule until progression of tumor (arm A) or a program of FOLFOX7 for 6 cycles, followed by maintenance without oxaliplatin for 12 cycles, and reintroduction of FOLFOX7 (arm B). Response rates were comparable at 58.5% and 59.2% for arms A and B, respectively. Likewise, median PFS and survival times did not differ significantly, but fewer patients in arm B reported high-grade toxicities. The OPTIMOX2 study (N=187) then compared the FOLFOX7 schedule of OPTIOMX1 to a program of FOLFOX7 for 6 bimonthly cycles with complete cessation of therapy and reintroduction of FOLFOX7, prior to rebound of tumor to baseline. Reported median PFS times for OPTIMOX1/ OPTIMOX2 were 36/28 weeks (P = .01), with a PFS in responders of 41/30 weeks (P = .001). A strong trend for increased survival with the OPTIMOX1 strategy also emerged (median overall survival of 26 vs 19 months; P = .0549) (4406, 4407). Summary: Colorectal cancer (CRC) is a major health concern in the US, affecting nearly 6% of the population within their lifetime, and over half of those diagnosed will either present with or progress to an advanced stage (4337). The incidence also promises to rise as a factor of age with increasing longevity (4261). While surgical resection is paramount, chemotherapy presently offers substantial patient benefits, even if disease is unresectable or metastatic. The recent emergence of newer cytotoxic drugs, novel biologic agents, and a more liberal treatment milieu has significantly improved overall survival rates for CRC, relative to historical standards (4348). Given the current pace of therapeutic research, further advances are fully expected. The imperative now is to establish effective delivery strategies that optimize therapeutic outcomes in the wake of change. \\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\ Constipation: Rome III Criteria for Constipation Presence of 2 or more of the following: 1. Straining in ≥ 25% of defecations 2. Lumpy or hard stool in ≥ 25% defecations 3. Sensation of incomplete evacuation in ≥ 25% of defecations 4. Sensation of anorectal obstruction/blockade in ≥ 25% defecations 5. Manual maneuvers to facilitate ≥ 25% defecations (eg, digital evacuation, pelvic floor support) 6. Fewer than 3 defecations per week Additional criteria: 1. Stool rarely loose without the use of laxatives 2. Criteria insufficient to indicate irritable bowel syndrome Treatment of constipation Tables on how to treat constipation: http://www.uptodate.com/patients/content/image.do?file=gast_pix/treatm66.htm Subcutaneous mehylnaltrexone (Relistor) rapidly induce laxation in patients with advanced illness and opioid-induced constipation. Treatment did not appear to affect central analgesia or precipitate opioid withdrawal. Dosage: 0.15 mg/kg qod sc x 2 weeks Crohn's Disease: (Also see IBD) Debra Helper study @IU 278-7097 Prochymal i.v. infusion; study volunteers must be 1. age 18-70 inclusive; have ileocolitis, colitis or ileitis; have tried steroids, immunosuppressive drugs and biologic drugs within the past two years and had no response, lost response or could not tolerate these meds. Remicade infusions up in Carmel: Shideler Dermatology office 755 West Carmel Dr. Ste 101 Carmel, IN 46032 317-846-2396; Fax 317-846-1699 Humira link: http://www.humira.com/ Dosage link: http://www.humira.com/CrohnsDisease/DosingAndInjection/Default.aspx Prescription 1: Humira Crohn's disease starter package Dispense 1 pack (6 x 40 mg pens) Inject four (4) Pens (160 mg) SC on Day 1, Followed by two (2) Pens (80 mg) SC on Day 15 refills: none Prescription 2: Humira Pen: Dispense 1 box (2x 40 mg pens) Inject one (1) pen (40 mg) sc every other week refills ____ Humira vs. Remicaide vs. Cimzia Complications of TNF: Information for Healthcare Professionals: Cimzia (certolizumab pegol), Enbrel (etanercept), Humira (adalimumab), and Remicade (infliximab) FDA ALERT [9/4/2008]: FDA is notifying healthcare professionals that histoplasmosis and other invasive fungal infections are not consistently recognized in patients taking tumor necrosis factor-α blockers (TNF blockers), Cimzia (certolizumab pegol), Enbrel (etanercept), Humira (adalimumab), and Remicade (infliximab). This has resulted in delays in appropriate treatment, sometimes resulting in death. FDA has received reports of patients developing pulmonary and disseminated histoplasmosis, coccidioidomycosis, blastomycosis and other opportunistic infections while taking TNF blockers. In some patients, the diagnosis of histoplasmosis was initially unrecognized and antifungal treatment was delayed. Some of these patients died from histoplasmosis. There were also deaths in patients with coccidioidomycosis and blastomycosis. For patients taking TNF blockers who present with signs and symptoms of possible systemic fungal infection, such as fever, malaise, weight loss, sweats, cough, dypsnea, and/or pulmonary infiltrates, or other serious systemic illness with or without concomitant shock, healthcare professionals should ascertain if patients live in or have traveled to areas of endemic mycoses. For patients at risk of histoplasmosis and other invasive fungal infections, clinicians should consider empiric antifungal treatment until the pathogen(s) are identified. Consultation with an infectious diseases specialist should be sought when feasible. As with any serious infection, consider stopping the TNF blocker until the infection has been diagnosed and adequately treated. FDA will require the makers of the tumor necrosis factor-α blockers (TNF blockers) to further highlight the information about the risk of invasive fungal infections, such as histoplasmosis, in the Boxed Warning and Warnings sections of the drugs’ prescribing information and the Medication Guide for patients. FDA will also require that the makers of the TNF blockers educate prescribers about this risk. This information reflects FDA's current analysis of data available to FDA concerning this drug. FDA intends to update this sheet when additional information or analyses become available. To report any unexpected adverse or serious events associated with the use of these drugs, please contact the FDA MedWatch program either online, by regular mail or by fax, using the contact information at the bottom of this page. Considerations for Healthcare Professionals TNF blockers are immunosuppressants. Patients taking TNF blockers are at risk for developing invasive fungal infections such as histoplasmosis, coccidioidomycosis, blastomycosis, aspergillosis, candidiasis, and other opportunistic infections. Healthcare practitioners should be alert to these risks of TNF blockers in patients who live in regions of endemic mycoses. Patients should be closely monitored during and after treatment with TNF blockers for the development of signs and symptoms of possible systemic fungal infection including fever, malaise, weight loss, sweats, cough, dypsnea, pulmonary infiltrates on X-ray, or serious systemic illness including shock. Patients who develop an infection should have their TNF blocker discontinued and undergo a complete diagnostic workup, which may include fungal cultures, histopathological or cytological evaluations, antigen detection and serum antibody titers. For patients who reside or travel in regions where mycoses are endemic, invasive fungal infections should be suspected if they develop the signs and symptoms of possible systemic fungal infection. The decision to administer empiric antifungal therapy in these patients should be made in consultation with an infectious diseases specialist with expertise in the diagnosis and treatment of invasive fungal infections when feasible. TNF blockers may be restarted after recovery from the infection. The decision to restart the TNF blocker should include a reevaluation of the benefits and risks of TNF blockers, especially in patients who live in regions of endemic mycoses. Both the decision to restart TNF blocker therapy and the duration of antifungal therapy should be made in consultation with an infectious disease specialist, when feasible. Information for the Patient Prescribers should discuss the following information with patients and their caregivers: Patients treated with TNF blockers have an increased risk for infections. Some patients have had serious infections while receiving TNF blockers. In some cases, patients needed to be hospitalized for treatment. These serious infections include infections caused by viruses, fungi, or bacteria including tuberculosis (TB), including infections that have spread throughout the body. Some patients have died from these infections. If you have weight loss, persistent fever, sweating, cough, shortness of breath, or fatigue, promptly seek medical attention. Tell your doctor where you live and about recent travel in and outside the USA. The risk of some infections is greater in regions where different microorganisms (bacteria, fungi, viruses, parasites) are more common. Tell your doctors that you are taking a TNF blocker. A doctor may make different decisions about your medical treatment if he or she knows that you are taking a TNF blocker. Tell your doctor about all of your medical conditions, including if you have an infection that won't go away or a history of an infection that keeps coming back. Background Information and Data TNF blockers suppress the immune system by blocking the activity of TNF, a substance in the body that can cause inflammation and lead to immune system-related diseases. There are currently four TNF blockers available in the United States: Cimzia, Enbrel, Humira, and Remicade. The TNF blockers have demonstrated benefit and are each approved to treat one or more of a number of immune system diseases including juvenile idiopathic arthritis (JIA), rheumatoid arthritis, psoriatic arthritis, plaque psoriasis, Crohn’s disease, and ankylosing spondylitis. Remicade is approved for use in children to treat Crohn’s disease. Enbrel and Humira are approved for use in children to treat JIA. Since TNF blockers are immunosuppressants, patients that take these drugs are at increased risk of serious infections, including invasive fungal infections such as histoplasmosis, coccidioidomycosis, blastomycosis, aspergillosis, candidiasis, cryptococcosis, as well as other opportunistic infections. Since the initial approval of the four TNF blockers, the prescribing information for these drugs has included information about the risk of serious infections, including fungal infections. However, based on the reports reviewed by FDA, healthcare professionals are not consistently recognizing cases of histoplasmosis and other invasive fungal infections, leading to delays in treatment. Some patients with invasive fungal infections have died. FDA reviewed 240 reports of histoplasmosis in patients receiving Remicade (207 cases), Enbrel (17 cases), or Humira (16 cases). The majority of cases were from Histoplasma capsulatum-endemic areas in the Ohio and Mississippi River valleys. In at least 21 of the reports, histoplasmosis was initially unrecognized and antifungal treatment was delayed. Twelve of these 21 patients died. FDA has reviewed 1 reported case of histoplasmosis in a patient taking Cimzia, which was approved in April 2008. FDA has also received reports of cases, including deaths, of coccidioidomycosis and blastomycosis in patients receiving TNF blockers. Management of Crohn’s Disease in Adults (February 2009) Clostridium difficile C diff vaccine: http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=148861
Diagnosis and Management of C. difficile-Associated Diarrhea and Colitis (May 1997)
D-----------------------------D Diabetes Gastroparesis:
http://www.practicalgastro.com/pdf/June09/HejaziArticle.pdf
Dry oropharynx 1. a high-fluoride toothpaste like Fluoridex or Colgate’s Provident 5000+ to help reduce decay. extreme, uncomfortable dry mouth at night? 2. Try Biotene relief of dry mouth, including an artificial saliva spray that you can keep next to your bed on your night table. If you awaken during the night with dry mouth, give your mouth a couple of quick spritzes of Biotene’s product and go back to sleep. 3. Salagen ( Pilocarpine). Taken four times a day, Salagen pills have been shown to provide significantlyincreased saliva flow and relief of dry mouth. Saliva flow can start to increase as soon as 20 minutes after you take Salagen and the increase can last for 3 to 5 hours. Peak effectiveness is about an hour after you take Salagen. Since it’s difficult to eat when your mouth is very dry, many people time their Salagen dose to be taken an hour before mealtimes. Since Salagen may cause fluctuations in blood pressure or heart rate, you should be closely supervised by an M.D. 4. chew gum or sour candy. If your candy or gum contains sugar you can set yourself up forrapidly-spreading tooth decay 5.Look for sugarless candy with xylitol. If you chew this gum for five minutes after every meal, studies show that you can reduce the incidence of tooth decay up to 62%. 6. Sjogren’s, go to www.sjogrens.org. They put out a monthly newsletter called “The Moisture Seekers.” 7. Getting a lot of dry mouth, particularly when it gets cold and air is dry in the house...try Prevident and Biotene to moisten your mouth.
Drugs: GI DRUGS: Humira link: http://www.humira.com/; dosage: Prescription 1: Humira Crohn's disease starter package Dispense 1 pack (6 x 40 mg pens) Inject four (4) Pens (160 mg) SC on Day 1,Followed by two (2) Pens (80 mg) SC on Day 15; Prescription 2: Dispense 1 box (2x 40 mg pens)Inject one (1) pen (40 mg) sc every other week Procrit (Epoetin alfa), Aranesp (darbepoetin alfa), Epogen (Epoetin alfa): There are reports of antibody-mediated pure red cell aplasia (PRCA) and transfusion-dependant anemia in patients with HCV infection wo receive treatment with ribavirin and interferon and an erythropoiesis-stimulating agent concurrently.Diarrhea Acute Infectious Diarrhea in Adults (November 1999); Vibrio infection:http://www.practicalgastro.com/pdf/May09/StiversArticle.pdf
Diverticular Disease
Diagnosis and Management of Diverticular Disease of the Colon in Adults (November 1999) Dyspepsia: Management of Dyspepsia (October 2005) E-----------------------------------------E ERCP: Episod study: This is being done by Evan Fogel 317-278-6997; Laura Lazzell-Pannell 317-278-3119; Suzette Schmidt RN 278-8104 email efogel@iupui.edu Main criteria are 1. ccy >3 months ago; negative CT or MRCP, bile duct less than or equal to 9mm; EGD with no relevant pathology with negative HP testing, or eradication; near normal LFT's, amylase, lipase; pain persistent despite treatment with PPi and trial of anti-spasmodics; no daily narcotics (less than 15 days per month); no prior sphincterotomy or biliary diversion surgery; no major psyche issues; no prior pancreatitis EPISOD link: http://www.episod.org/
http://video.google.com/videosearch?hl=en&source=hp&q=ercp%20sphincterotomy&um=1&ie=UTF-8&sa=N&tab=wv# ERCP advanced procedures
http://daveproject.org/ViewPresentation.cfm?film_id=511&CFID=2737738&CFTOKEN=41402088
http://www.filmbaby.com/films/2907
Patient information: http://video.google.com/videosearch?hl=en&source=hp&q=ercp%20sphincterotomy&um=1&ie=UTF-8&sa=N&tab=wv#q=ercp+&hl=en&view=2&emb=0 http://daveproject.org/ViewFilms.cfm?Film_id=36
Cholangiocarcinoma
http://daveproject.org/ViewFilms.cfm?Film_id=22
http://daveproject.org/ViewFilms.cfm?Film_id=313http://daveproject.org/ViewFilms.cfm?Film_id=37http://daveproject.org/ViewFilms.cfm?Film_id=30
http://daveproject.org/ViewFilms.cfm?Film_id=27
http://daveproject.org/ViewFilms.cfm?Film_id=35
http://daveproject.org/viewfilms.cfm?film_id=857
Laser for ERCP stones: http://video.google.com/videosearch?hl=en&source=hp&q=ercp%20sphincterotomy&um=1&ie=UTF-8&sa=N&tab=wv#q=ercp+&hl=en&view=2&emb=0&start=70
http://daveproject.org/ViewFilms.cfm?Film_id=377
http://video.google.com/videosearch?hl=en&source=hp&q=ercp%20sphincterotomy&um=1&ie=UTF-8&sa=N&tab=wv#q=ercp+&hl=en&view=2&emb=0&start=110http://video.google.com/videosearch?hl=en&source=hp&q=ercp%20sphincterotomy&um=1&ie=UTF-8&sa=N&tab=wv#q=ercp+&hl=en&view=2&emb=0&start=120NIHhttp://video.google.com/videosearch?hl=en&source=hp&q=ercp%20sphincterotomy&um=1&ie=UTF-8&sa=N&tab=wv#q=ercp+&hl=en&view=2&emb=0&start=120
NIH concensus on ERCP:Trying to avoid acute pancreatitis:
Risk factors for AP with ERCP:
Esophageal Cancer Esophageal Cancer (December 1999) Esophageal HIV Diseases Diagnosis and Treatment of Esophageal Diseases Associated with HIV Infection (November 1996) F---------------------------------------F Fecal Incontinence
Diagnosis and Management of Fecal Incontinence (2004)
Fulminant Hepatic Failure Major causes of FHF: Tylenol, hep A, autoimmune hepatitis, hep B, Hep c, cryptogenic cirrhosis, Hep D, drugs, wilson's, Budd-Chiari syndrome, acute fatty liver of pregnancy, Reye's syndrome, various drugs and toxins: acetaminophen/etoh/amio/carbon tetrachloride/dideoxyinosine/gold/halothane/isoniazide/ketoconazole/MAO inhibitors/methldopa/NSAIDs/phenytoin/poison mushrooms amanita phalloides/propylthiouracil/ rifampin/ sulfonamides/tetracycline/tricyclic antidepressants/valproic acid A good table that summarizes causes: http://knol.google.com/k/-/-/4ptrsx4j4vcq/8ajlpl/slide1.jpg King´s College Hospital Criteria for Liver Transplantation in Fulminant Hepatic Failure 1. Acetaminophen-induced disease Arterial pH <7.3>100 seconds, and Serum creatinine >3.4mg/dl (301 ?mol/L) 2. All other causes of fulminant hepatic failure Prothrombin time >100 seconds (irrespective of the grade of encephalopathy) or Any three of the following variables (irrespective of the grade of encephalopathy) Age <10>40 years Etiology: non-A, non-B hepatitis, halothane hepatitis, idiosyncratic drug reactions Duration of jaundice before onset of encephalopathy >7 days Prothrombin time >50 seconds Serum bilirrubin >18 mg/dl In patients with non-acetaminophen acute liver failure, the following criteria were identified as being associated with a poor prognosis:[2] INR greater than 6.5; or, Three of the following five criteria: Patient age of less than 11 or greater than 40; Serum creatinine of greater than 3.4; Time from onset of jaundice to the development of coma of greater than seven days; INR greater than 3.5; or, Drug toxicity, regardless of whether it was the cause of the acute liver failure. Failure of Kings College criteria: an interesting case: http://www.turner-white.com/pdf/hp_sep01_failure.pdf G--------------------------------------G Gastroparesis Sx: abd pain,hb,postpradial fullness,nausea, bloating, vomiting, unintended wt loss; Diff Dx: PUD, GERD, Gastric outlet obstruction; Workup: EGD, Solid GES, consdier SBS; Treatment: small frequent meals (6-8 per day), low residue, low fat diet (fat delays gastric emptying, low residue helps prevent bezoar), consider liquid nutritional supplements, Meds: reglan (potential side effects restless, drowsy, parkinsonism, lowers sz threshold, tardive dyskinesia), motilium, EES (more effective i.v.), po dose 100 mg suspension tid, phenergan, compazine, ondasetron; consider J tube, consider gastric stimulator implant, control sugars if DM GERD Esophageal Reflux Testing (March 2007)Diagnosis and Treatment of Gastroesophageal Reflux Disease (January 2005)GI bleed Management of the Adult Patient with Acute Lower Gastrointestinal Bleeding (August 1998) GIST www.pvupdate.com/gist21/p/205 H------------------------------------------------H Helicobacter pylori: Management of Helicobacter pylori Infection(August 2007) Hepatic Encephalopathy Hepatic Encephalopathy (July 2001) Hepatitis B: Good flow sheets for pts with HBeAg negative CHB and HBeAg positive CHBhttp://images.google.com/imgres?imgurl=http://bdliverjournal.com/wp-content/uploads/2009/05/hbeagve.jpg&imgrefurl=http://bdliverjournal.com/%3Fpage_id%3D35&usg=__TblevTxpKFiVXhpVDt5ruIOgBno=&h=927&w=706&sz=76&hl=en&start=27&um=1&tbnid=RmXkIIfAL7YLMM:&tbnh=147&tbnw=112&prev=/images%3Fq%3Dhepatitis%2Bb%252Brecommendations%2Bin%2Bpatients%2Bwith%2BHBeag-negative%2Bchb%26ndsp%3D20%26hl%3Den%26sa%3DN%26start%3D20%26um%3D1 http://www.nature.com/ajg/journal/v101/n1s/full/ajg2006557a.html#fig2 Hepatitis C: http://www.projectsinknowledge.com/Activity/vwodsimulcast.cfm?jn=1937&action=viewed®=success Hepatitis C protocol: http://hcv.org.nz/wordpress/wp-content/uploads/2009/07/treatemnt-flowchart.jpg Possible future therapy: DDW: Telaprevir Improves HCV Clearance in Resistant Patients http://www.medpagetoday.com/tbindex.cfm?tbid=14515 Sustained Response Seen with New Hepatitis C Drug (Dr. Kwo) http://www.medpagetoday.com/tbindex.cfm?tbid=13894 Treatment with Pegasys vs. PEG-IFN Studies that reveal no differences: 1. http://www.ncbi.nlm.nih.gov/pubmed/19853954?itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum&ordinalpos=1 Rx choice in HIV/Hep C 2. http://www.ncbi.nlm.nih.gov/pubmed/19363085?itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum&ordinalpos=3 3. http://www.ncbi.nlm.nih.gov/pubmed/19119244?itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum&ordinalpos=4 4. http://www.ncbi.nlm.nih.gov/pubmed/18422960?itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum&ordinalpos=10 5.In previous nonresponders: http://www.ncbi.nlm.nih.gov/pubmed/18416586?itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum&ordinalpos=11 6. No differences in cost or efficacy with SVR: http://www.ncbi.nlm.nih.gov/pubmed/17542764?itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum&ordinalpos=13 7. No differences (by Dr. Rumi who in the abstract listed below said PegIFN-alfa 2a was better)http://www.ncbi.nlm.nih.gov/sites/entrez My questions: Was there something wrong with the MIST study and it was never published? On Google, I can't find the 2 abstracts given to me: 1. Randomized study comparing Peginterferon-alfa2a plus Ribavarin and Peginterferon-alfa 2b plus Ribavirin in naive patients with chronic hepatitis C: final results of the Milan Safety Tolerability (MIST) study. by M.Rumi et al 2. Peginterferon alpha-2A plus ribavirin versus peginterferon alpa-2b plus rivavirin in naive patients with chronic hepatitis c virus infection: results of a prospective randomised trial. by A. Ascione et al Predictors of better response per Hepatology. 2007 Jul;46(1):37-47. Predictors of increased likelihood of genotype 1 patients having an SVR were low-level HCV viremia, elevated ALT quotient, and receiving PEG-INF 2A (rather than 2B). For genotype 2 patients, increasing body mass index, prior use of interferon, and low platelet count were negative predictors; only low-level HCV viremia was a positive predictor. ***Excellent Hep C therapy: The Effective Physicain:Background, Conclusions, Implementation Hepatitis C.(THE EFFECTIVE PHYSICIAN)(Disease/Disorder overview) Management of Hepatitis C: 1. HCVAb+ 2. Check liver w/u labs including quantitiative HCVRNA, genotype 3. determine the log of the HCVRNA http://www.hepatitis-central.com/hcv/hepatitis/loadchart.html 4. Stop ETOH 5. Stop TOB 6. Gradual wt loss if NAFLD, DM, Hyperlipidemia and if fatty liver on the biopsy. If DM versus fatty liver consider Metformin: http://www.medpagetoday.com/tbindex.cfm?tbid=11662; Also, Diet May Influence Risk of Liver Disease: http://www.medpagetoday.com/tbindex.cfm?tbid=14960; It's also been proven that Fatty Liver Disease Responds to Extra Exercise http://www.medpagetoday.com/tbindex.cfm?tbid=14969 7. Avoid iron and vitamin C supplements (Vit C helps absorb iron) 8. Vaccinate for Hep A/Hep B 9. If acute HCV (detected 1-3 weeks post infection) antiviral Rx is effective (98% SVR) with unmodified interferon 5 million units daily for 4 weeks followed by t.i.w. to complete a 24 week course. Delaying Rx for 2-4 months after transmission to identify persons who achieve spontaneous clearance has bee advocated by some to avoid unneccesary tx in acute setting. 10. Think about extrahepatic manifestations of Hep C i.e. extrahepatic mixed cryoglbulinemia (EMC), present in 15% in the US. Only a small percent of these pts have sx. Sx include purpura, weakness, arthralgia, MPGN, peripheral neuropathy, Raynauds. Antiviral Rx is main Rx. Of note, steroids, cyclophosphamide, plasmapharesis, have been used with EMC pts who present with rapid MPGN or severe necrotizing vasculitis to stabilize this process prior to Rx of HCV. Other extrahepatic manifestations include Lichen planus, PCT, nonHodgkin's B-cell lymphoma 11. Discuss side effects: IFN: HA, fevers, rigors, musculoskeletal pain, fatigue, neutropenia, thrombocytopenia, anemia, N, V, decreased appetite, diarrhea, depression, irritable, decreased concentration, insomnia, injection site inflammation, alopecia, pruritus, thyroid dysfunction Ribavarin: Hemolytic anemia, rash, pruritus, cough, dyspnea, anoerexia, nausea, insomnia, teratogenic. Neither women or men should conceive 6 months after taking the last dose. Best response: non genotype 1, low HCV count i.e. <2x10(6)>I---------------------------------------I IBS history: Constipation, diarrhea, abdominal pain, bloating, worse with menses; worse postprandial, foods postprandial that worsen symptoms; At least 3 months, with onset at least 6 months previously of recurrent abdominal pain or discomfort** associated with 2 or more of the following: Improvement with defecation; and/or Onset associated with a change in frequency of stool; and/or Onset associated with a change in form (appearance) of stool IBS: Rome III criteria: http://cme.medscape.com/viewarticle/533460 (david4med) J--------------------------------------J K-------------------------------------K L--------------------------------------LLiver Disease in the Pregnant Patient (July 1999)--also see Pregnancy
M------------------------------------M
Modified Barium Swallow: If abnormal do: 1.Throat exercises: http://www.kennedysdisease.org/disc_tips_throat.html 2.Laryngeal exercises: http://medicalcenter.osu.edu/PatientEd/Materials/PDFDocs/exer-reh/upper/larynx-strength-exer.pdf N-------------------------------------N NASH: Prevention of NSAID-Related Ulcer Complications (March 2009)--also see PUD and DrugsNutrition
1. See TPN calculator above. 2. Detailed patient directions: http://www.trafford.nhs.uk/files/file/pdf/patient%20information%20leaflets/Nutrition/Managing%20your%20enteral%20feeding%20gastrostomy%20tube.pdf O-------------------------------------O Osteoporosis
Risks: Sedentary lifestyle, low BMI, tob, +FHx, low calcium intake, low Vitamin D intake, lack of sun exposure, IBD, use of steroids RX: calcium, vitamin D, biphosphonates, hormone therapy or a combination. alendronate= Fosamax etidronate (not approved by FDA for osteoporosis)= Didronel ibandronate = Boniva risedronate = Actonel risedronate with calcium carbonate = (Actonel with Calcium) zoledronic acid = Reclast P--------------------------------------P Acute Pancreatitis Acute Pancreatitis (October 2006) APACHE II score http://www.globalrph.com/apacheii.htm Ranson's criteria http://www.mdcalc.com/ransons-criteria-for-pancreatitis-mortality Treatment regimen: Corpak, nutrition, IVF, ?antbx, CT scan, follow labs, workup Primary Biliary Cirrhosis PBC-AIH overlap syndrome http://www.ncbi.nlm.nih.gov/pubmed/16356577 Overlap defined as 1. ALT >5x ULN 2: IgG > 2 x ULN or positive ASMA and 3) moderate to severe lobular inflammation on pretreatment liver biopsy Q--------------------------------------Q R--------------------------------------R ROS GI Review of Systems GI bleed: upper? lower? bright red? melena? clots? amount? Duration, frequency, quantitiy, N/V/retching? syncope? LH? hypotension? syptoms? early satiety? h/o bleed, h/o nose bleeds? h/o tics, hemorrhoids, colitis, PUD, Hematemesis, easy bruising, bleeding diseases or family h/o bleeding (Factor VII deficiency, Factor XI deficiency, Hemophilia, vonWillebrand's disease), CAD, renal disease, cirrhosis, alcohol use, NSAIDS, ASA, coumadin, Plavix, heparin, lovenox? Upper GI Bleed http://enotes.tripod.com/ugibleed.htm Lower GI Bleed http://enotes.tripod.com/lgibleed.htm Abdominal pain: Duration, location, time of progression, radiation? associated with other sx? triggering factors? intensity (1-10), needle like? sharp? pressure? spasm? dull? Constant? intermittent? how often? sudden? gradual? postprandial? improved by___? bloating? constipation? diarrhea? related to menses? past abdominal surgery? worse with inspiration?N/V: color, character, frequency, duration? early satiety? abd pain? vertigo? tinnitus? pregnancy. Wt loss/Anoerexia: amount of wt loss, change in appetite, N/V/dysphagia/abd pain postprandial/dental problems/h/o CVA? Constipation/obstruction? N/V, obstipation, distention, crampy abd pain, previous abd surgery? narcotics? personal or FHx h/o colon polyps? colon CA? wt loss? Diarrhea: Duration, frequency, volume, #stools/day, watery/soft/loose? fever? cramps? bloating? flatus? urgency? blood? mucous? oil? Recent possibly spoiled poultry,eggs,milk (Salmonella); fried rice (cornybacterium), seafood (Vibrio), recent resturants? Travel hx? laxative abuse? recent Mg, sulfa, antbx, cholinergics, colchicine, milk? Ill contact with diarrhea? FHx sprue, IBD? AIDS risk factors blood tx, IVDA, anal sex, homosexual? IBS symptoms? C/D/worse with menses?/bloating? lower abd pain/ cramping? Hepatitis: Fatigue/RUQ pain/anorexia/jaundice/ pruritis/arthralgias/myalgia/N/V/ fever/ dark urine/pale or white stools/increased abd girth/rash/fatigue/somnolence/wt loss/FHx liver dz (Hemachromatosis, Wilson's, etc...), day care center visit, travel, prior hepatitis immunization, raw seafood/tylenol/phenytoin/tegretol/INH/alcohol/blood tx/tatoo/IVDA/(w/ autoimmune hepatitis: above and skin rash, hirsuitism, amenorrhea, cushingoid features, chest pain from pleuitis), possibly pregnant? Cirrhosis: 1. varices: http://www.jhep-elsevier.com/article/PIIS0168827803000114/fulltext2. Beta-blocker: propranolol tid 3. Encephalopathy Rx 4. Hepatocellular w/u alpha-fetoprotein, hepatoma protocol 5. Ascites? Prophylaxis for SBP? Pancreatitis: Constant/dull/boring/midepigastric/ LUQ? radiation/ exacerbated when supine? Relieved by sitting with knees down/ pain relievers/ dyspnea/h/o ETOH/ gallstones?/ US/CT/MRI/ERCP? postoperative? triglycerides,Ca, renal failure, Coxsackie virus, Mumps, Mycoplasma, Lupus? vasculitis? PUD, scorpion bite? tumor? MEDS FASTVET S--------------------------------------S Skin Diseases: Dercum's (inflammation of fatty nodules): http://www.dercumsociety.com/ ;Tinea versicolor; Small bowel disease: Imaging of Small Bowel Disease: Comparison of Capsule Endoscopy, Standard Endoscopy, Barium Examination and CT; http://radiographics.rsnajnls.org/cgi/content/figsonly/25/3/697 T--------------------------------------T TPN http://epen.kumc.edu/ U-------------------------------------U Ulcerative Colitis in Adults (July 2004) V-------------------------------------V W-----------------------------------W X-------------------------------------X Y-------------------------------------Y Z-------------------------------------Z
