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HCV Treatment Guidelines
The American Association for the Study of Liver Diseases (AASLD) and the Infectious Disease Society of America (IDSA) published guidelines for the treatment of HCV. These HCV Treatment Guidelines will be published in hard copy in Hepatology and in the Journal of Infectious Diseases. The full report can already be accessed as a PDF file.
Detailed discussions guide the clinician according to the HCV genotype, past treatment failures or responses, and interferon ineligibility.
Some important points to remember: Patients receiving antiviral therapy require careful pretreatment assessment for comborbidities that may influence treatment response. All patients should have careful monitoring during treatment, particularly for anemia if ribavirin is included in the regimen. Some regimens should be considered only in those patients who require immediate treatment, as it is anticipated that safer and more effective IFN-free regimens will become available by 2015.
1. Regimens are classified as either
- “Recommended” when it is favored for most patients or
- “Alternative” when optimal in a particular subset of patients in that category, or
- “Not Recommended” when a treatment is clearly inferior or is deemed harmful. Such regimens should not be administered to patients with HCV infection.
2. Interferon ineligible is defined as one or more:
- Intolerance to IFN
- Autoimmune hepatitis and other autoimmune disorders
- Hypersensitivity to PEG or any of its components
- Decompensated hepatic disease
- History of depression, or clinical features consistent with depression
- A baseline neutrophil count below 1500/μL, a baseline platelet count below 90,000/μL or baseline hemoglobin below 10 g/dL
- A history of preexisting cardiac disease
3. Specific considerations are addressed in other sections of the document:
- HIV/HCV coinfection
- Compensated and decompensated cirrhosis (moderate or severe hepatic impairment)
- Post-liver transplant HCV
- Patients with severe renal impairment or ESRD
A) INITIAL TREATMENT OF HCV INFECTION IN PATIENTS STARTING TREATMENT for
This section provides guidance on the recommended initial treatments for persons with chronic HCV infection who are naive to HCV treatment or who have achieved an undetectable level of virus during a prior treatment course of PEG/RBV and relapsed (relapsers) according to genotype.
- Genotype 1
- Genotype 2
- Genotype 3
- Genotype 4
- Genotype 5 or 6
A Summary Table of Recommendations for patients who are initiating therapy for HCV infection or who experienced relapse after prior PEG/RBV therapy by HCV genotype is provided.
This section provides guidance on the retreatment of a person with chronic HCV infection in whom prior therapy has failed, addressing non-responders, which includes null responders (those in whom serum HCV RNA levels declined less than 2 log10 IU/mL by week 12 during a prior treatment course) and partial responders according to genotype.
- Genotype 1
- Genotype 2
- Genotype 3
- Genotypes 4, 5 and 6
A Summary Table of Recommendations for patients in whom previous PEG/RBV treatment has failed is provided.
C) UNIQUE PATIENT POPULATIONS ARE FURTHER ADDRESSED:
The recommendations are a MUST-READ for all providers who care for patients with HCV infection.
Guideline on the Use of Thiopurines, Methotrexate, and Anti–TNF-a Biologic Drugs for the Induction and Maintenance of Remission in Inflammatory Crohn’s Disease
The American Gastroenterological Association published new guidelines on the use of Thiopurines, Methotrexate, and anti–TNF biologic drugs for the induction and maintenance of remission in Crohn’s Disease. Selecting among immunomodulator monotherapy, anti-TNF-alpha monotherapy and combination therapy is a clinical dilemma. The AGA decision support tool (gastro.org/crohnsdecisiontool) and guidelines on the use of immunomodulators and anti-TNF-alpha biologic agents in inducing and maintaining clinical remission in patients with inflammatory (luminal) Crohn’s disease is of considerable value. The technical review is also available for review, which offers an in-depth analysis of the existing research informing the clinical recommendations.
Recommendations for the induction of remission:
1. The AGA suggests against using thiopurine monotherapy to induce remission in patients with moderately severe Crohn’s disease.
2. The AGA suggests against using methotrexate to induce remission in patients with moderately severe Crohn’s disease.
3. The AGA recommends using anti-TNF-alpha drugs to induce remission in patients with moderately severe Crohn’s disease.
4. The AGA recommends using anti-TNF-alpha monotherapy over thiopurine monotherapy to induce remission in patients who have moderately severe Crohn’s disease.
5. The AGA recommends using anti-TNF-alpha drugs in combination with thiopurines over thiopurine monotherapy to induce remission in patients who have moderately severe Crohn’s disease.
6. The AGA suggests using anti-TNF-alpha drugs in combination with thiopurines over anti-TNF-alpha drug monotherapy to induce remission in patients who have moderately severe Crohn’s disease.
Recommendations for maintenance of remission:
1. The AGA recommends using thiopurines over no immunomodulator therapy to maintain a steroid-induced remission in patients with Crohn’s disease.
2. The AGA suggests using methotrexate over no immunomodulator therapy to maintain a steroid-induced remission in patients with Crohn’s disease.
3. The AGA suggests using anti-TNF-alpha drugs over no anti-TNF-alpha drugs to maintain a steroid or anti-TNF-alpha drug-induced remission in patients with Crohn’s disease.
4. The AGA makes no recommendation for or against the combination of an anti-TNF-alpha drug and a thiopurine versus an anti-TNF-alpha drug alone to maintain remission induced by a combination of these drugs in patients with Crohn’s disease.
http://download.journals.elsevierhealth.com/pdfs/journals/0016-5085/PIIS0016508513015217.pdf
http://download.journals.elsevierhealth.com/pdfs/journals/0016-5085/PIIS0016508513015205.pdf
Guidelines for Follow-up of Colorectal Cancer Patients
- Which evaluations (eg, colonoscopy, computed tomography [CT], carcinoembryonic antigen [CEA], liver function, complete blood count [CBC], chest x-ray, history, and physical examination) should be performed for surveillance for recurrence of cancer?
- What is a reasonable frequency of these evaluations for surveillance?
- Which symptoms and/or signs potentially signify a recurrence of CRC and warrant investigation?
- What are the common and/or significant long-term and late effects of CRC treatment?
- On what secondary prevention measures should CRC survivors be counseled?
- The target population for these guidelines included CRC survivors (adult patients who have completed primary treatment for stage II or III CRC and who are without evidence of disease). Whether these recommendations are extrapolated to stage I patients or a patient with metastatic CRC who underwent metastatectomy and is currently without evidence of disease, is left to the discretion of the health care provider.
- The target audience for these guidelines include clinicians (eg, medical oncologist, radiation oncologist, surgeon, advanced practice nurse, physician assistant, primary care provider [family physician, nurse practitioner, family practice nurse]) involved in the delivery of care for CRC patients, families of patients who have survived CRC, and health care organizations and system leaders responsible for offering, monitoring, or providing resources for CRC survivorship protocols.
- Surveillance should be guided by presumed risk of recurrence and functional status of patient where early detection would lead to aggressive treatment including surgery. It is especially important in the first 2 to 4 years, when the risk of recurrence is the greatest.
- A medical history, physical examination, and CEA testing should be performed every 3 to 6 months for 5 years. The frequency of visits and testing should be driven by the data showing that 80% of recurrences occur in the first 2 to 2.5 years from date of surgery and 95% occur by 5 years. Patients at a higher risk of recurrence should be considered for testing in the more frequent end of the range.
- Abdominal and chest imaging using a CT scan is recommended annually for 3 years. For high-risk patients, it is reasonable to consider imaging every 6 to 12 months for the first 3 years. Outside of a clinical trial, PET scans are not recommended for surveillance.
- For patients with rectal cancer, a pelvic CT is also recommended. Clinician judgment, considering risk status, should be used to determine the frequency of pelvic scans (eg, annually for 3 to 5 years). For those patients who have not received pelvic radiation, a rectosigmoidoscopy should be performed every 6 months for 2 to 5 years.
- A surveillance colonoscopy should be performed approximately 1 year after the initial surgery. The frequency of subsequent surveillance colonoscopies should be dictated by the findings of the previous one, but they generally should be performed every 5 years if the findings of the previous one are normal. If a complete colonoscopy was not performed before diagnosis, a colonoscopy should be done as soon as reasonable after completion of adjuvant therapy and not necessarily at the 1-year time point.
- Any new and persistent or worsening symptoms warrant the consideration of a recurrence.
- Despite the lack of high-quality evidence on secondary prevention in CRC survivors, it is reasonable to counsel patients on maintaining a healthy body weight, being physically active, and eating a healthy diet.
- A treatment plan from the specialist should be sent to the patient’s other providers, particularly the primary care physician, and it should have clear directions on appropriate follow-up.
- If a patient is not a surgical candidate or a candidate for systemic therapy because of severe comorbid conditions, surveillance tests should not be performed.
The ASCO Panel wants to highlight that the recommendations are primarily for patients with stage II or III cancer. There are insufficient data to provide guidance for follow-up for stage I patients or patients with resected metastatic disease with no evidence of disease. The ASCO Panel emphasizes that surveillance tests should only be performed in patients in whom the results will change treatment decisions. If a patient is not a surgical candidate or a candidate for systemic therapy because of severe co-morbid conditions, surveillance tests should not be performed.
Clinical Practice Guideline for Vaccination of the Immunocompromised Host
The Infectious Diseases Society of America (IDSA), published online December 5, 2013 in Clinical Infectious Diseases an important paper which will help providers guide immunocompromised patients in choosing the right vaccinations: “2013 IDSA Clinical Practice Guideline for Vaccination of the Immunocompromised Host”
The guidelines were created to provide primary care and specialty clinicians with evidence-based guidelines for active immunization of patients with altered immunocompetence and their household contacts in order to safely prevent vaccine-preventable infections. The goal of these guidelines is to decrease morbidity and mortality from vaccine-preventable infections in immunocompromised patients. This guideline addresses children and adults with primary (congenital) immune deficiencies; patients with secondary immune deficiencies due to HIV infection, cancers associated with immune deficiency, cancer chemotherapy, stem cell or solid organ transplant (SOT), sickle cell diseases, and surgical asplenia; and patients with chronic inflammatory diseases treated with systemic corticosteroid therapy, immunomodulator medications, and/or biologic agents. Vaccination of immunocompetent patients who have an anatomic host defense abnormality (eg, cerebrospinal fluid [CSF] leak) associated with vaccine-preventable infections and of individuals living in a household with immunocompromised patients is also addressed.
Utah Gastroenterology has summarized important parts of these guidelines as they pertain to patients with Inflammatory Bowel Disease or Solid Organ Transplantation. The guideline focus on vaccines available in the United States, which are often relevant to other areas.
The following clinical questions are answered:
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Who is responsible for vaccinating immunocompromised patients and members of their household?
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When should vaccines be administered to immunocompetent patients in whom initiation of immunosuppressive medications is planned?
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Which vaccines can be safely administered to individuals living in a household with immunocompromised patients, and what precautions should immunocompromised patients observe after vaccination of household members?
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Which vaccines can be administered to immunocompromised patients contemplating international travel?
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Should immunocompromised patients or those scheduled to receive immunosuppressive therapy receive varicella vaccine (VAR)?
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Should immunocompromised patients or those who will undergo immunosuppression receive zoster vaccine (ZOS)?
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Should immunocompromised patients receive influenza vaccine?
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For adult and child Solid Organ Transplantation (SOT) candidates and living donors, which vaccines should be administered during pretransplant evaluation?
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Which vaccines should be administered to SOT recipients?
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Which vaccines should be administered to patients with chronic inflammatory diseases maintained on immunosuppressive therapies?
RECOMMENDATIONS FOR VACCINATION
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Specialists who care for immunocompromised patients share responsibility with the primary care provider for a) ensuring that appropriate vaccinations are administered to immunocompromised patients and b) for recommending appropriate vaccinations for members of immunocompromised patients’ household.
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Vaccines should be administered prior to planned immunosuppression if feasible.
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Live vaccines should be administered ≥4 weeks prior to immunosuppression and should be avoided within 2 weeks of initiation of immunosuppression.
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Inactivated vaccines should be administered ≥2 weeks prior to immunosuppression.
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Immunocompetent individuals who live in a household with immunocompromised patients can safely receive inactivated vaccines based on the CDC–ACIP’s annually updated recommended vaccination schedules for children and adults or for travel.
- Individuals who live in a household with immunocompromised patients age ≥6 months should receive influenza vaccine annually. They should receive either:
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Inactivated influenza vaccine (IIV) or
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Live attenuated influenza vaccine (LAIV) provided they are healthy, not pregnant, and aged 2–49 years. Exceptions include individuals who live in a household with an immunocompromised patient who was a hematopoietic stem cell transplant (HSCT) recipient within 2 months after transplant or with graft vs host disease (GVHD) or is a patient with severe combined immune deficiency (SCID).* In these exceptions, LAIV should not be administered or, if administered, contact between the immunocompromised patient and household member should be avoided for 7 days.
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Healthy immunocompetent individuals who live in a household with immunocompromised patients should receive the following live vaccines based on the CDC annual schedule: combined measles, mumps, and rubella (MMR) vaccines; rotavirus vaccine in infants aged 2–7 months; varicella vaccine (VAR); and zoster vaccine (ZOS). Also, these individuals can safely receive the following vaccines for travel: yellow fever vaccine and oral typhoid vaccine.
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Oral polio vaccine (OPV) should not be administered to individuals who live in a household with immunocompromised patients.
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Highly immunocompromised patients should avoid handling diapers of infants who have been vaccinated with rotavirus vaccine for 4 weeks after vaccination.
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Immunocompromised patients should avoid contact with persons who develop skin lesions after receipt VAR or ZOS until the lesions clear
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Clinicians may administer inactivated vaccines indicated for travel based on the CDC annual schedule for immunocompetent adults and children.
- Yellow fever vaccine generally should not be administered to immunocompromised persons.
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With certain exceptions live vaccines should not be given to immunocompromised persons.
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VAR should be given to immunocompetent patients without evidence of varicella immunity (ie, age-appropriate varicella vaccination, serologic evidence of immunity, clinician-diagnosed or -verified history of varicella or zoster, or laboratory-proven varicella or zoster) if it can be administered ≥4 weeks before initiating immunosuppressive therapy.
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A 2-dose schedule of VAR, separated by >4 weeks for patients aged ≥13 years and by ≥3 months for patients aged 1–12 years, is recommended if there is sufficient time prior to initiating immunosuppressive therapy.
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VAR should not be administered to highly immunocompromised patients.
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VAR can be considered for patients without evidence of varicella immunity who are receiving long-term, low-level immunosuppression.
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VAR should be administered to eligible immunocompromised patients as the single antigen product, not VAR combined with MMR vaccine.
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ZOS should be given to patients aged ≥60 years if it can be administered ≥4 weeks before beginning highly immunosuppressive therapy.
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ZOS should be considered for varicella-positive patients (ie, persons with a history of varicella or zoster infection or who are varicella–zoster virus [VZV] seropositive with no previous doses of VAR) aged 50–59 years if it can be administered ≥4 weeks before beginning immunosuppressive therapy.
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ZOS should be administered to patients aged ≥60 years who are receiving therapy considered to induce a low level of immunosuppression.
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ZOS should not be administered to highly immunocompromised patients.
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Annual vaccination with IIV is recommended for immunocompromised patients aged ≥6 months except for patients who are very unlikely to respond (although unlikely to be harmed by IIV), such as those receiving intensive chemotherapy or those who have received anti–B-cell antibodies within 6 months.
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LAIV should not be administered to immunocompromised persons.
VACCINATION OF PATIENTS ON IMMUNOSUPPRESSIVE MEDICATIONS
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Inactivated vaccines, including IIV, should be administered to patients with chronic inflammatory illness treated or about to be treated with immunosuppressive agents as for immunocompetent persons based on the CDC annual schedule.
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Pneumococcal vaccine should be administered to adults and children with a chronic inflammatory illness that is being treated with immunosuppression.
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VAR should be administered to patients with chronic inflammatory diseases without evidence of varicella immunity ≥4 weeks prior to initiation of immunosuppression if treatment initiation can be safely delayed.
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VAR should be considered for patients without evidence of varicella immunity being treated for chronic inflammatory diseases with long-term, low-level immunosuppression.
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ZOS should be administered to patients with chronic inflammatory disorders who are aged ≥60 years prior to initiation of immunosuppression or being treated with low-dose immunosuppression and those who are aged 50–59 years and varicella positive prior to initiation of immunosuppression or being treated with low-dose immunosuppression.
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Other live vaccines should not be administered to patients with chronic inflammatory diseases on maintenance immunosuppression: LAIV, MMR vaccine in patients receiving low-level and high-level immunosuppression; and MMRV vaccine in patients receiving low-level and high-level immunosuppression.
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Other recommended vaccines, including IIV and HepB vaccine, should not be withheld because of concerns about exacerbation of chronic immune-mediated or inflammatory illness.
VACCINATION OF SOLID ORGAN TRANSPLANT RECIPIENTS
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Living donors should be current with vaccines based on age, vaccination history, and exposure history according to the CDC annual schedule; MMR, MMRV, VAR, and ZOS vaccine administration should be avoided within 4 weeks of organ donation. Vaccination of donors solely for the recipient’s benefit is generally not recommended.
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Adults and children with chronic or end-stage kidney, liver, heart, or lung disease, including solid organ transplant (SOT) candidates, should receive all age-, exposure history-, and immune status-appropriate vaccines based on the CDC annual schedule for immunocompetent persons.
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Adult SOT candidates; adults with end-stage kidney disease; and pediatric patients who are SOT candidates; are aged <6 years and have end-stage kidney, heart, or lung disease; or are aged 6–18 years and have end-stage kidney disease should receive pneumococcal vaccine.
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Adults and children aged ≥2 years who are SOT candidates or have end-stage kidney disease should receive pneumococcal vaccine if they have not received a dose within 5 years and have not received 2 lifetime doses. Patients with end-stage kidney disease should receive 2 lifetime doses 5 years apart. Adults and children aged ≥2 years with end-stage heart or lung disease as well as adults with chronic liver disease, including cirrhosis, should receive a dose of pneumococcal vaccine if they have never received a dose. When both PCV13 and PPSV23 are indicated, PCV13 should be completed 8 weeks prior to PPSV23.
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Anti-HBs–negative SOT candidates should receive the HepB vaccine series and, if on hemodialysis and aged ≥20 years, they should receive the high-dose (40 µg) HepB vaccine series. If a postvaccination anti-HBs concentration of ≥10 mIU/mL is not attained, a second 3-dose series of HepB vaccine (alternative: 1 dose of HepB vaccine after which anti-HBs is tested) should be administered, using standard dose or high dose* for children and high dose for adolescents and adults. HepA-unvaccinated, -undervaccinated, or -seronegative SOT candidates (particularly liver transplant candidates) aged 12–23 months and ≥2 years should receive a HepA vaccine series.
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Combined HepA–HepB vaccine can be used for SOT candidates aged ≥12 years of age in whom both vaccines are indicated.
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The HPV vaccine series should be administered to SOT candidates aged 11–26 years.
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SOT candidates aged 6–11 months can receive MMR vaccine if they are not receiving immunosuppression and if transplantation is not anticipated within 4 weeks. If transplantation is delayed (and the child is not receiving immunosuppression), the MMR vaccine should be repeated at 12 months.
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The VAR should be administered to SOT candidates without evidence of varicella immunity if they are not receiving immunosuppression and if transplantation is not anticipated within 4 weeks. The VAR can be administered to varicella-naive SOT candidates aged 6–11 months who are not immunosuppressed provided the timing is ≥4 weeks prior to transplant. Optimally, 2 doses should be administered ≥3 months apart.
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SOT candidates aged ≥60 years and varicella-positive candidates aged 50–59 years who are not severely immunocompromised should receive ZOS if transplantation is not anticipated within 4 weeks.
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Vaccination should be withheld from SOT recipients during intensified immunosuppression, including the first 2-month posttransplant period, because of the likelihood of inadequate response. However, IIV can be administered ≥1 month after transplant during a community influenza outbreak.
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Standard age-appropriate inactivated vaccine series should be administered 2 to 6 months after SOT based on the CDC annual schedule, including IIV.
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Pneumococcal vaccine PCV13 should be administered 2 to 6 months after SOT if not administered before SOT, with the timing based on the patient’s degree of immunosuppression.
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For SOT patients aged ≥2 years, 1 dose of pneumococcal vaccine PPSV23 should be administered 2 to 6 months after SOT, with the timing based on the patient’s degree of immunosuppression, and ≥8 weeks after indicated doses of pneumococcal vaccine PCV13, if not given within 5 years and if the patient has received no more than 1 previous lifetime dose.
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HepB vaccine should be considered for chronic HepB-infected recipients 2 to 6 months after liver transplant in an attempt to eliminate the lifelong requirement for HepB immune globulin (HBIG.
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MMR vaccine and VAR should generally not be administered to SOT recipients because of insufficient safety and effectiveness data, except for varicella in children without evidence of immunity who are renal or liver transplant recipients, are receiving minimal or no immunosuppression, and have no recent graft rejection.
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Vaccination should not be withheld because of concern about transplant organ rejection.
Management of Acute Pancreatitis
The current guidelines on the diagnosis and treatment of acute pancreatitis as published in the American Journal of Gastroenterology by the American College of Gastroenterology are summarized below.
IN SUMMARY:
During the past decade, there have been new understandings and developments in the diagnosis, etiology, and early and late management of the disease. As the diagnosis of AP is most often established by clinical symptoms and laboratory testing, contrast-enhanced computed tomography and/or magnetic resonance imaging of the pancreas should be reserved for patients in whom the diagnosis is unclear or who fail to improve clinically. Hemodynamic status should be assessed immediately upon presentation and resuscitative measures begun as needed. Patients with organ failure and/or the systemic inflammatory response syndrome (SIRS) should be admitted to an intensive care unit or intermediary care setting whenever possible. Aggressive hydration should be provided to all patients, unless cardiovascular and/or renal comorbidites preclude it. Early aggressive intravenous hydration is most beneficial within the first 12-24 h, and may have little benefit beyond. Patients with AP and concurrent acute cholangitis should undergo endoscopic retrograde cholangiopancreatography (ERCP) within 24 h of admission. Pancreatic duct stents and/or postprocedure rectal nonsteroidal anti-inflammatory drug (NSAID) suppositories should be utilized to lower the risk of severe post-ERCP pancreatitis in high-risk patients. Routine use of prophylactic antibiotics in patients with severe AP and/or sterile necrosis is not recommended. In patients with infected necrosis, antibiotics known to penetrate pancreatic necrosis may be useful in delaying intervention, thus decreasing morbidity and mortality. In mild AP, oral feedings can be started immediately if there is no nausea and vomiting. In severe AP, enteral nutrition is recommended to prevent infectious complications, whereas parenteral nutrition should be avoided. Asymptomatic pancreatic and/or extrapancreatic necrosis and/or pseudocysts do not warrant intervention regardless of size, location, and/or extension. In stable patients with infected necrosis, surgical, radiologic, and/or endoscopic drainage should be delayed, preferably for 4 weeks, to allow the development of a wall around the necrosis.
DEFINITIONS OF SEVERITY IN ACUTE PANCREATITIS – Atlanta Revision (2013):
1. Mild acute pancreatitis
- Absence of organ failure
- Absence of local complications
2. Moderately severe acute pancreatitis
- Local complications AND/OR
- Transient organ failure (<48 h)
3. Severe acute pancreatitis
- Persistent organ failure >48 hrs
CLINICAL FINDINGS ASSOCIATED WITH A SEVERE COURSE FOR INITIAL RISK ASSESSMENT:
1. Patient characteristics:
- Age > 55 years
- Obesity (BMI > 30 kg/m2)
- Altered mental status
- Comorbid disease
2. The systemic inflammatory response syndrome (SIRS) – Presence of >2 of the following criteria:
- pulse >90 beats/min
- REspirations >20/min or PaCO2 >32 mm Hg
- temperature >38 ° C or <36 °C
- WBC count >12,000 or <4,000 cells/mm3 or >10% immature neutrophils (bands)
3. Laboratory findings
- BUN >20 mg/dl
- Rising BUN
- HCT > 44%
- Rising HCT
- Elevated creatinine
4. Radiology findings
- Pleural effusions
- Pulmonary infiltrates
- Multiple or extensive extra-pancreatic collections
SUMMARY OF RECOMMENDATIONS:
1. DIAGNOSIS
- The diagnosis of AP is most often established by the presence of two of the three following criteria:
- abdominal pain consistent with the disease
- serum amylase and/or lipase greater than three times the upper limit of normal, and/or
- characteristic findings from abdominal imaging
- Contrast-enhanced computed tomographic and/or magnetic resonance imaging of the pancreas should be reserved for patients in whom the diagnosis is unclear or who fail to improve clinically within the first 48-72 h after hospital admission
2. ETIOLOGY
- Transabdominal ultrasound should be performed in all patients with acute pancreatitis
- In the absence of gallstones and/or history of significant history of alcohol use, a serum triglyceride should be obtained and considered the etiology if > 1,000 mg/dl
- In a patient older than 40 years, a pancreatic tumor should be considered as a possible cause of acute pancreatitis
- Endoscopic investigation in patients with acute idiopathic pancreatitis should be limited, as the risks and benefits of investigation in these patients are unclear
- Patients with idiopathic pancreatitis should be referred to centers of expertise
- Genetic testing may be considered in young patients (<30 years old) if no cause is evident and a family history of pancreatic disease is present
3. INITIAL ASSESSMENT AND RISK STRATIFICATION
- Hemodynamic status should be assessed immediately upon presentation and resuscitative measures begun as needed
- Risk assessment should be performed to stratify patients into higher- and lower-risk categories to assist triage, such as admission to an intensive care setting
- Patients with organ failure should be admitted to an intensive care unit or intermediary care setting whenever possible
4. INITIAL MANAGEMENT
- Aggressive hydration, defined as 250-500 ml per hour of isotonic crystalloid solution should be provided to all patients, unless cardiovascular and/or renal comorbidites exist. Early aggressive intravenous hydration is most beneficial the first 12-24 h, and may have little benefit beyond
- In a patient with severe volume depletion, manifest as hypotension and tachycardia, more rapid repletion (bolus) may be needed
- Lactated Ringer’s solution may be the preferred isotonic crystalloid replacement fluid
- Fluid requirements should be reassessed at frequent intervals within 6 h of admission and for the next 24-48 h. The goal of aggressive hydration should be to decrease the blood urea nitrogen
5. ERCP IN ACUTE PANCREATITIS
- Patients with acute pancreatitis and concurrent acute cholangitis should undergo ERCP within 24 h of admission
- ERCP is not needed in most patients with gallstone pancreatitis who lack laboratory or clinical evidence of ongoing biliary obstruction
- In the absence of cholangitis and/or jaundice, MRCP or endoscopic ultrasound (EUS) rather than diagnostic ERCP should be used to screen for choledocholithiasis if highly suspected
- Pancreatic duct stents and/or postprocedure rectal nonsteroidal anti-inflammatory drug (NSAID) suppositories should be utilized to prevent severe post-ERCP pancreatitis in high-risk patients
6. THE ROLE OF ANTIBIOTICS IN ACUTE PANCREATITIS
- Antibiotics should be given for an extrapancreatic infection, such as cholangitis, catheter-acquired infections, bacteremia, urinary tract infections, pneumonia
- Routine use of prophylactic antibiotics in patients with severe acute pancreatitis is not recommended
- The use of antibiotics in patients with sterile necrosis to prevent the development of infected necrosis is not recommended
- Infected necrosis should be considered in patients with pancreatic or extrapancreatic necrosis who deteriorate or fail to improve after 7-10 days of hospitalization. In these patients, either
- initial CT-guided fine needle aspiration (FNA) for Gram stain and culture to guide use of appropriate antibiotics or
- empiric use of antibiotics without CT FNA should be given
- In patients with infected necrosis, antibiotics known to penetrate pancreatic necrosis, such as carbapenems, quinolones, and metronidazole, may be useful in delaying or sometimes totally avoiding intervention, thus decreasing morbidity and mortality
- Routine administration of antifungal agents along with prophylactic or therapeutic antibiotics is not recommended
7. NUTRITION IN ACUTE PANCREATITIS
- In severe AP, enteral nutrition is recommended to prevent infectious complications. Parenteral nutrition should be avoided unless the enteral route is not available, not tolerated, or not meeting caloric requirements
- Nasogastric delivery and nasojejunal delivery of enteral feeding appear comparable in efficacy and safety
8. THE ROLE OF SURGERY IN ACUTE PANCREATITIS
- In patients with mild AP, found to have gallstones in the gallbladder, a cholecystectomy should be performed before discharge to prevent a recurrence of AP
- In a patient with necrotizing biliary AP, in order to prevent infection, cholecystectomy is to be deferred until active inflammation subsides and fluid collections resolve or stabilize
- The presence of asymptomatic pseudocysts and pancreatic and/or extrapancreatic necrosis do not warrant intervention, regardless of size, location, and/or extension
- In stable patients with infected necrosis, surgical, radiologic, and/or endoscopic drainage should be delayed preferably for more than 4 weeks to allow liquefication of the contents and the development of a fibrous wall around the necrosis (walled-off necrosis)
- In symptomatic patients with infected necrosis, minimally invasive methods of necrosectomy are preferred to open necrosectomy
Achalasia
The current guidelines on the diagnosis and treatment of achalasia as published in the American Journal of Gastroenterology by the American College of Gastroenterology are summarized below.
Achalasia is an incurable disease with an incidence of 1/100,000 occurring equally among men and women. Achalasia is characterized by insufficient relaxation of the lower esophageal sphincter and loss of esophageal peristalsis, leading to difficulty in swallowing with dysphagia to solids and liquids, regurgitation, and occasional chest pain with or without weight loss. Achalasia is often misdiagnosed as gastroesophageal reflux disease (GERD). Achalasia must be suspected in those with dysphagia to solids and liquids and in those with regurgitation unresponsive to an adequate trial of proton pump inhibitor (PPI) therapy.
Endoscopic finding of retained saliva with a puckered gastroesophageal junction or a barium swallow showing a dilated esophagus with birds beaking in a symptomatic patient should prompt appropriate diagnostic and therapeutic strategies.
Graded pneumatic dilation or laparoscopic surgical myotomy with a partial fundoplication are recommended as initial therapy for the treatment of achalasia. Surgical myotomy has shown excellent results in most patients and remains the surgery of choice, with more being done laparoscopically. The benefit of adding a fundoplication was demonstrated and a cost–utility analysis found that myotomy plus fundoplication was more cost effective than myotomy alone. Retreatment of patients is likely required within 5 years; retreatment should be individualized based on local expertise.
The guidelines also call for follow-up for symptom relief and esophagus emptying results through use of barium esophagram. Endoscopy surveillance for esophageal cancer is not recommended.
DIAGNOSIS OF ACHALASIA
- All patients with suspected achalasia who do not have evidence of a mechanical obstruction on endoscopy or esophagogram should undergo esophageal motility testing before a diagnosis of achalasia can be confirmed.
- The diagnosis of achalasia is supported by esophagogram findings including dilation of the esophagus, a narrow esophago-gastric junction with “ bird-beak ” appearance, aperistalsis, and poor emptying of barium.
- Barium esophagogram is recommended to assess esophageal emptying and esophago-gastric junction morphology in those with equivocal motility testing.
- Endoscopic assessment of the gastroesophageal junction and gastric cardia is recommended in all patients with achalasia to rule out pseudoachalasia.
TAILORED APPROACH TO TREATING ACHALASIA
- Either graded pneumatic dilation (PD) or laparoscopic surgical myotomy with a partial fundoplication are recommended as initial therapy for the treatment of achalasia in those fit and willing to undergo surgery.
- PD and surgical myotomy should be performed in high-volume centers of excellence.
- The choice of initial therapy should be guided by patients’ age, gender, preference, and local institutional expertise.
- Botulinum toxin therapy is recommended in patients who are not good candidates for more definitive therapy with PD or surgical myotomy.
- Pharmacologic therapy for achalasia is recommended for patients who are unwilling or cannot undergo definitive treatment with either PD or surgical myotomy and have failed botulinum toxin therapy.
PATIENT FOLLOW-UP
- Patient follow-up after therapy may include assessment of both symptom relief and esophageal emptying by barium esophagogram.
- Surveillance endoscopy for esophageal cancer is not recommended.
In summary the new guidelines for diagnosis include:
- Performing an esophageal motility test on all patients suspected of having achalasia (the manometric findings of irregular muscle contractions and incomplete lower esophageal sphincter relaxation without mechanical obstruction establish the diagnosis of achalasia in the appropriate setting);
- Using esophagogram findings to support a diagnosis;
- Using an esophagogram for patients with equivocal motility testing;
- Using endoscopic assessment of the gastroesophageal junction and gastric cardia to rule out pseudoachalasia.
Treatment recommendations offer a tailored approach:
- Initial therapy should be either graded pneumatic dilation (PD) or laparoscopic surgical myotomy with a partial fundoplication in patients fit to undergo surgery;
- Procedures should be performed in high-volume centers of excellence;
- Initial therapy should be based on patient age, sex, preference, and local institutional expertise;
- Botulinum toxin therapy is recommended for patients not suited for PD or surgery;
- Pharmacologic therapy can be used for patients not undergoing PD or myotomy and who have failed botulinum toxin therapy (nitrates and calcium channel blockers are most commonly used).
Fecal Incontinence
Introduction:
Fecal incontinence is a difficult yet seldom talked about problem. The impaired ability to control gas or stool ranges from mild (difficulty with gas) to severe (loss of control of liquid and formed stools); symptoms can be continuous or recurrent. Nearly 18 million U.S. adults – about one in 12 – suffer from fecal incontinence. This number is likely underestimated as patients are reluctant to discuss this disabling problem. Incontinence causes emotional distress, loss of dignity, embarrassment, shame, frustration, anger, depression as well as social isolation. Perianal skin irritation may lead to pain, itching, and ulcers which may require medical or surgical treatments.
Causes of fecal incontinence include:
- diarrhea
- constipation
- muscle or nerve damage (due to constant straining, spinal cord injury, stroke)
- childbirth related trauma (episiotomy, forceps)
- anal operations
- traumatic injuries
- rectocele (a weakness of the recto-vaginal septum allows rectal tissue to bulge into the vagina. Rectoceles are uncommon in men as the prostate gland provides structural support)
- rectal prolapse
- inflammation (colitis)
- radiation
- tumors
- diseases such as diabetes, multiple sclerosis
- dementia (the prevalence of fecal incontinence is estimated at 47% for nursing home residents )
- aging (the prevalence of fecal incontinence is estimated at 15% in those 70 or older)
Other risk factors further include:
- poor general health
- physical disabilities
- chronic obstructive pulmonary disease
- irritable bowel syndrome
- urinary incontinence
- colectomy
- chronic diarrhea
- fecal impaction
- depression
Anorectal function and continence depend on factors such as stool volume, stool consistency, colonic transit, rectal distensibility, anal sphincter function, anorectal sensation and intact anorectal reflexes. Anatomical structures which help preserve continence include the rectum, the internal and external anal sphincter muscles, and the pubo-rectalis muscle. Defecation is initiated when stool enters the rectum, leading to rectal distention with reflex relaxation of the internal anal sphincter. The urge to defecate increases as more stool passes into the rectum. During defecation the anorectal angle is straightened and abdominal pressure is increased; pelvic floor descent, rectal contraction, and external anal sphincter relaxation then lead to emptying of stool.
Workup:
To better understand incontinence, a detailed history, physical exam and supplemental studies are required.
The clinical history should assess for onset of disease, duration, frequency, severity, precipitating events, and look for a history of difficult or traumatic vaginal delivery, anorectal surgery, pelvic irradiation, diabetes, and neurologic diseases.
A physical exam should include inspection of the perianal area which may reveal dermatitis (suggesting chronic incontinence), fistulizing disease, prolapsing hemorrhoids, or even rectal prolapse. Perianal sensation should be tested, with the absence of an anal wink reflex suggesting nerve damage. A digital rectal exam may provide information about the resting anal sphincte tone and may detect obvious anal pathology such as masses or fecal impaction . Inspection of the anus, rectum and large intestine via anoscopy, flexible sigmoidoscopy or colonoscopy may help to exclude mucosal inflammation, masses, or other pathology.
Anorectal manometry measures resting anal pressures, amplitude and duration of squeeze pressures, the rectoanal inhibitory reflex, threshold of conscious rectal sensation, rectal compliance, and anal rectal pressures during straining. Rectal sensation can be assessed by balloon inflation. Pudendal nerve terminal latency may assess potential nerve damage.
Endorectal ultrasound and magnetic resonance imaging are helpful to define structural abnormalities of the anal sphincters, the rectal wall, and the puborectalis muscle.
Defecography assesses anorectal anatomy at rest and during defecation; it assesses the anorectal angle, pelvic descent and may detect occult or overt rectal prolapse.
Intervention:
Three treatment approaches are commonly used for fecal incontinence:
- medical therapy such as dietary changes (i.e. avoidance of sphincter relaxing foods), constipating medications (treatment of diarrhea) and bulking agents (to enhance stool control)
- biofeedback and muscle strengthening exercises
- surgery, such a surgical sphincter muscle repair or implantation of an artificial anal sphincter
Medical therapy should be aimed at reducing stool frequency and improving stool consistency. Specific treatment for the underlying cause of diarrhea should be implemented, as formed stool is easier to control than liquid stool. While stool consistency can be improved with bulking agents (i.e. fiber supplements, bile binders), this may exacerbate incontinence in patients with decreased rectal compliance (i.e. in radiation proctitis or rectal stricture).
Stool frequency can be reduced with antidiarrheals such as loperamide (Imodium®) or diphenoxylate (Lomotil®); anticholinergic agents i.e. hyoscyamine (Levsin®, NuLev®, Anaspaz®, Levsinex®, Levbid®) may help with postprandial leakage if taken before meals.
Patients with fecal impaction should be disimpacted and treated with a bowel training regiment to prevent recurrent impaction.
Pelvic floor exercise and biofeedback may help retrain pelvic floor and abdominal wall musculature and may enhance the ability to sense rectal distention, thereby improving sensory as well strength components required for continence. Pelvic floor exercises involve squeezing and relaxing pelvic floor muscles 50-100 times a day. A health care provider can help with proper technique. Biofeedback therapy may help to perform these exercises properly and may improve anorectal sensation. Biofeedback uses special anal and rectal pressure sensors, as well as rectal balloons to produce graded sensations of rectal fullness. Measurements are displayed on a video screen and are used to modify or change abnormal function. Success depends on the cause of fecal incontinence, its severity, and the person’s ability to follow instructions; the role of biofeedback in the management of fecal incontinence is still debated, as the optimal protocol, equipment, and duration of treatment are undefined.
Surgical approaches to fecal incontinence include direct sphincter repair, plication of the posterior part of the sphincter, anal encirclement, implantation of an artificial sphincter, and muscle transfer procedures with or without electrical stimulation. Patients with a sphincter tear (obstetric trauma, fistula surgery) can be cured with a sphincteroplasty. It is the most common fecal incontinence surgery and reconnects the ends of a torn sphincter muscle.
A synthetic sphincter device or magnetic anal sphincter may be available in highly specialized centers. The Acticon (TM) neosphincter, consisting of an occlusive cuff (implanted around the anal canal), a pressure-regulating balloon (implanted in the prevesical space) and a control pump (implanted in the labium or scrotum) enables users to squeeze the control pump to permit defecation.
Sacral nerve electrical stimulation may restore continence in patients with structurally intact muscles. This approach appears to be effective in patients with neurologic disorders. The FDA approved the sacral nerve stimulator (InterStim®, Medtronics) for the treatment of chronic fecal incontinence in patients who have failed or are not candidates for more conservative treatments.
Injectable materials allow augmentation of the function of the internal anal sphincter. Injection of dextranomer-hyaluronic acid (Solesta®), used for the treatment of urinary incontinence, has also been approved for patients with fecal incontinence.
Anal plugs have been studied as a possible treatment for fecal incontinence. Fecal incontinence improved only in a minority of patients, anal plugs were poorly tolerated and their usefulness is thereby limited.
In extreme cases patients may need a colostomy to improve quality of life as a colostomy may be the only option for patients with intractable symptoms who are not candidates for any other therapy, or in whom other treatments have failed.
Lynch Syndrome (Hereditary Nonpolyposis Colorectal Cancer)
Guidelines for the management of Lynch syndrome (HNPCC) are summarized and adapted from recommendations of US and European experts.
Introduction
Although a family history of colon cancer increases an individual’s risk of colon cancer by two-to-threefold, some families have a very significantly increased cancer risk due to proven genetic mutations. While most patients with a family history of colon cancer may be surveilled with a 5-yearly screening protocol (typically starting at age 40 or 10 years before the index relative’s disease), these special families require a much closer surveillance interval and consideration for multiple other cancers. Two major genetic conditions to be considered are Familial Adenomatous Polyposis (FAP) and Lynch Syndrome (LS).
Lynch syndrome (LS), also called hereditary nonpolyposis colorectal cancer (HNPCC), is an autosomal dominant disorder caused by a germline mutation in one of several DNA mismatch repair (MMR) genes. It is the most common inherited colon cancer susceptibility syndrome, accounting for approximately 1–3% of all colorectal cancers (CRC). The name HNPCC can be misleading as this disorder predisposes to multiple cancers:
- colon cancer (risk ~25–70%)
- endometrial cancer (EC) (risk ~30–70%)
- stomach cancer
- ovarian cancer
- bladder cancer
- upper urologic tract cancers (renal pelvis, ureter)
- small bowel cancer
- biliary/pancreatic cancer
- skin cancer (sebaceous adenomas, carcinomas and keratoacanthomas)
- brain cancers
- possible prostate cancer
The frequency of extracolonic cancers in LS varied from 2-20%. LS is responsible for about 2 percent of all endometrial cancers. There is some debate whether even breast cancers may be part of the LS.
Clinical features/genetics
Early age of onset and multiplicity of cancers have been considered hallmarks of LS. 7-10% of LS patients have more than one cancer at diagnosis (i.e. synchronous CRC), metachronous CRC are also common (developing another CRC after an initial resection if a subtotal colectomy is not performed). The overall CRC rate appears moderately higher for men than women. LS is an autosomal dominant disorder caused by a defect in one of the mismatch repair (MMR) genes: MLH1, MSH2, MSH6 or PMS2.
- MLH1 (MutL homolog 1), located on chromosome 3p21
- MSH2 (MutS homolog 2), located on chromosome 2p16
- MSH6 (MutS homolog 6), located on chromosome 2p16
- PMS1 and PMS2 (postmeiotic segregation 1 and 2), located on chromosomes 2q31 and 7p22, respectively
These gene defects lead to a loss of MMR function and result in an accumulation of microsatellite mutations. These microsatellite instabilities (MSI) refer to an expansion or contraction of short repetitive DNA sequences (microsatellites) due to loss of DNA mismatch repair. These mutations lead to alterations in cancer related genes, likely driving the process of carcinogenesis. The overall cancer risk (~80%) and the colorectal cancer risk (50-70%) are similar in MLH1 and MSH2 families, but the risks of endometrial and other extracolonic cancers appear to be substantially higher in MSH2 families. Families with MSH6 and possibly PMS2 mutations appear to have an attenuated cancer phenotype (later age of cancer diagnosis and lower penetrance) compared to MLH1 and MSH2 families. Homozygous or compound heterozygous carriers of MLH1, MSH2, MSH6, or PMS2 often develop hematologic and brain malignancies during childhood. Most had a family history of LS on both the maternal and paternal sides of their families.
The term Lynch syndrome should only be used in individuals and families known to have a detectable MMR gene mutation. Individuals without gene testing are no longer labeled as having LS even if Amsterdam criteria are met.
Amsterdam criteria have been used to identify patients and families at risk for LS.
- “3-2-1 rule”: 3 affected members, 2 generations, 1 under age 50 – (3 or more relatives with LS-associated cancers (colorectal, endometrial or small bowel cancers, transitional cell carcinoma of the ureter or renal pelvis), one being a first degree relative of the other two, involvement of at least two generations, one or more cancers diagnosed before the age of 50).
Bethesda guidelines identify individuals with LS-associated cancers who should be tested for microsatellite instability (and MMR gene testing in those with MSI-H tumors). LS is suggested in colon cancer patients if certain characeristics are present such as young age and strong familial clustering of colon cancer. LS cancers appear to evolve from adenomas, tend to be larger, flatter, more proximal, and have high-grade dysplasia and/or villous histology, with a more rapid progression of the adenoma-carcinoma sequence. Cancers are more proximal, poorly differentiated , and often mucinous. Histologic features such as tumor-infiltrating lymphocytes, Crohn’s-like lymphocytic reaction, mucin/signet ring cell differentiation, and medullary growth pattern can be used to select patients who might have LS. These patients should have their colon cancers tested for microsatellite instability (if positive, proceed with germline MMR gene testing).
- Benefits of genetic testing in high risk families including a more accurate diagnosis and risk assessment as well as better implementation of surveillance protocols.
- Family members who do not need intensive surveillance can also be better identified; these members without high risk mutations carry a similar cancer risk as the general population and do not need heightened surveillance.
- Once high risk individuals are identified, germline testing is recommended in the affected individual. If possible, gene testing should be performed on the family member most likely to have the syndrome (i.e. the youngest family member with colorectal cancer).
- Practitioners should ensure that patients received appropriate counseling. Informed consent should include a general description of the test, the disorder to be tested for, the meaning of positive and negative results, and the level of certainty that a positive or negative test is a predictor of disease. Counseling about benefits of early cancer detection and prevention or treatment modalities should be offered.
Muir-Torre and Turcot Syndrome
Two variants of Lynch syndrome had been considered distinct entities: Muir-Torre (Lynch syndrome with associated sebaceous tumors, cutaneous keratoacanthomas, and visceral carcinomas) and Turcot syndrome (Lynch syndrome with associated brain tumors, typically gliomas). These families with extracolonic cancers (brain, sebaceous tumors, skin acanthomas, and visceral carcinomas) are considered part of the spectrum of LS.
General cancer surveillance in LS
Analysis of all causes of cancer deaths in LS revealed that 61% of cancer deaths were associated with non-CRC non-EC cancers. Testing of all patients (<70 years) with CRC or EC for loss of MMR function by means of MSI or immunohistochemistry has been recommended, as testing remains one of the first steps to identify individuals who are at increased risk for LS.
CRC surveillance
- Colorectal surveillance by regular colonoscopy is the only surveillance protocol proven to be effective. Due to advanced CRC in LS detected between 2 and 3 years after surveillance colonoscopy, an interval of 1-2 years is recommended. Colonoscopy is recommended to begin at age 20-25, or 10 years prior to the earliest age of colon cancer in the family (whichever comes first). In families with MSH6 mutations, surveillance starts at age 30, since onset of colon cancer is seen later in these families. Since the risk of developing a second CRC after partial colectomy for primary CRC is estimated at approximately 16% after 10 years (despite following close surveillance), more extensive surgery(total or subtotal colectomy) for the primary CRC might be considered.
EC surveillance
- Although the value of surveillance for EC is unclear, routine annual surveillance (gynecological exam, transvaginal ultrasound, biopsy starting at age of 35–40, or 5-10 years earlier than the earliest age of diagnosis of these cancers) may lead to early detection of premalignant disease or cancers and should be offered to mutation carriers. A CA 125 may be of benefit. Hysterectomy and bilateral oophorectomy prevents the development of endometrial and ovarian cancer and could be discussed with patients after the age of 35-40, who have completed their family planning. If CRC surgery is scheduled, prophylactic hysterectomy and bilateral oophorectomy at the same time should be considered.
Gastric cancer surveillance
- The cumulative risk of developing gastric cancer in LS by the age of 70 is approximately 5%. Most gastric cancers in LS are of the intestinal type, so regular EGDs may be of benefit. Given the relatively low risk of gastric cancer and the lack of established surveillance benefit, European guidelines advise against surveillance for gastric cancer.
Small bowel cancer surveillance
- The risk of developing small bowel cancer in carriers of an MLH1 or MSH2 mutation is approximately 5%. Currently European guidelines advise against surveillance for small bowel cancer, but inspection of the distal duodenum during upper endoscopy and ileum during colonoscopy (if performed) is recommended. Evaluation of the small bowel in patients with unexplained abdominal complaints or iron deficiency anemia has been suggested.
Urinary tract cancer surveillance
- Increased risks of bladder cancer as well as urothelial cancers of the upper urinary tract in LS have been demonstrated. Given lack of evidence of surveillance benefits for urinary tract cancer, European guidelines advise against surveillance for urinary tract cancer in LS.
Prostate cancer surveillance
- European guidelines do not recommend increased surveillance for prostate cancer in LS families outside of appropriate research studies.
Pancreatic cancer surveillance
- Recent studies have revealed an increased risk of developing pancreatic cancer in LS. Still, the benefit of surveillance for pancreatic cancer in high-risk groups is unknown and European guidelines advise against surveillance for this cancer in LS families.
Breast cancer surveillance
- Whether breast cancer is part of the tumor spectrum of LS is controversial. The cumulative risk by the age of 70 years may be 14% in all female carriers, with the highest risk in MLH1 carriers (MLH1: 17%; MSH2: 14.4%; MSH6: 11%). At present, female carriers of an MMR gene mutation should be advised to participate in population screening programs for breast cancer (biannual mammography from the age of 45 or 50) as per European guidelines. Since most patients with Lynch syndrome who develop breast cancer do so after the age of 50 years, standard screening approaches for breast cancer are likely appropriate.
In summary
As a practical expert opinion approach to surveillance strategies in LS, the reviewers for UpToDate® suggest annual colonoscopy starting at age 20-25 (or 10 years prior to the earliest age of colon cancer in a given family), annual screening for EC with endometrial biopsy and ovarian cancer with CA 125 as well as transvaginal ultrasound beginning at age 30-35 (or 5 to 10 years earlier than the earliest age of first diagnosis of these cancers, whichever is earlier), discussion of prophylactic hysterectomy and salpingo-oophorectomy at the end of childbearing, annual urinalysis beginning at age 25-35, annual skin surveillance and periodic upper endoscopy.
Gas and Bloating
Gas and bloating are common complaints for many patients, often quite bothersome and difficult to treat. Associated symptoms include belching, bloating, abdominal pain, constipation and flatulence, yet these are usually not due to “excess gas” production as commonly assumed.
A variety of diseases must be considered as a cause or contributing factor such as:
- Irritable Bowel Syndrome,
- Inflammatory Bowel Disease
- Celiac Disease
- Gastroparesis
- Superior Mesenteric Artery Syndrome
- Small Bowel Intestinal Overgrowth
- Disaccharide Deficiencies (i.e. Lactose Intolerance)
- Gastric Outlet Obstruction
- Post-Surgical States (i.e. Whipple, Roux-en-Y, ileo-colonic surgeries and anastomosis)
- Pancreatic Disases
- Aerophagia
- Rumination Syndrome
Complaints
If excessive gas is present, it may be due to swallowed air (aerophagia), increased intra-luminal gas production, decreased gas absorption (due to obstruction), or excessive gas intake such as with carbonated drinks.
- Aerophagia occurs if abnormal amounts of air are swallowed i.e. with food intake (due to poor dentures or rushed eating habits), due to anxiety, chewing gum and even due to smoking. Burping or belching is the way most swallowed air is expelled. The remaining gas moves into the small intestine where it is partially absorbed, while a small amount is released through the rectum. Studies have suggested that air may be swallowed into the esophagus rather than the stomach, resulting in excessive belching. This esophageal air can then easily be expelled, resulting in excessive belching.
- Increased intestinal gas can occur due to bacterial fermentation of non-digestible carbohydrates in the small bowel (small bowel bacterial overgrowth) or in the colon. Bacterial fermentation of ingested carbohydrates or proteins leads to hydrogen production, causing excessive gas. High concentrations of oligosaccharides or difficult to digest starches (flours made from wheat, oats, potatoes, and corn) lead to increased hydrogen production. This mechanism is the basis of the FODMAP diet, as malabsorption or maldigestion of carbohydrates may lead to increased intraluminal gas, complaints of abdominal pain and flatulence. These unabsorbed carbohydrates provide a substrate for rapid bacterial fermentation and lead to an increased osmotic load, altered gastrointestinal motility and a change in the profile of the bacterial flora. Furthermore patients with functional bowel disease (such as irritable bowel syndrome) may have a heightened sensitivity to the effects of malabsorbed carbohydrates, even though the rates of carbohydrate malabsorption may not differ from healthy subjects.
- To see a list of foods low and high FODMAP, visit the Australian-based MONASH University website, where this diet originated.
Diagnosis
Patients with bloating often lack an identifiable cause and can be classified as having a functional disorder.
- A careful history, physical exam and possibly a food diary review are the first important steps towards a diagnosis.
- Warning signs such as diarrhea, weight loss, abdominal pain, distention, anorexia or nutritional deficiency should prompt evaluation for other conditions such as inflammatory bowel disease, celiac disease or structural abnormalities as discussed above.
- Work up may include baseline laboratory testing, stool examination (fat, Giardia), a lactose tolerance test, celiac serology, and a small bowel radiograph vs. CT, an upper endoscopy and possibly a colonoscopy.
- Hydrogen breath testing may be used to assess for specific food issues and to test for small bowel bacterial overgrowth.
- Although abdominal distension is seen in patients with irritable bowel syndrome, an obstructing lesion should be considered.
- Pancreatic disease and cancer are in the differential, especially if malabsorption or steatorrhea are noted.
- Post surgical changes (i.e. Roux-en-Y, Whipple resection, ileo-colonic anastomoses etc) can lead to small bowel dysmotility as well as small bowel bacterial overgrowth. A cholecystectomy may lead to fat malabsorption due to lack of adequate bile presence, if larger fat-rich meals are consumed.
- Aerophagia can be diagnosed if troublesome repetitive belching at least several times a week is observed and/or if air swallowing is objectively noted.
Treatment
Treatment requires a multifactorial and often emperic approach.
- If aerophagia is suspected, then explaining this process to the patient may be beneficial.
- Discontinuation of habits such as gum chewing, smoking, drinking carbonated beverages, and gulping food and liquids as well as stress management may reduce the amount of ingested air. Eating at a slow pace and checking with a dentist to make sure dentures fit properly should also help.
- Avoidance of foods that may contribute to gas production is an initial step. This includes a temporary trial of lactose and fructose avoidance, avoidance of sorbitol (contained in diet foods and chewing gum), and avoidance of other gas-producing foods such as cabbage, onions, broccoli, brussel sprouts, wheat, and potatoes. This recommendation is part of the FODMAP diet (FODMAPs stands for Fermentable Oligo-, Di- and Mono-saccharides, and Polyols). FODMAPs include lactose in milk products, fructose and polyols found in fruits, fructans in wheat, onion or garlic, and galacto-oligosaccharides in beans and lentils. .
High FODMAP foods include
- fruits such as apples, apricots, cherries, mango, pears, nectarines, peaches, pears, plums, prunes, watermelon
- certain grains when consumed in large amounts such as rye, wheat
- lactose-containing foods such as custard, ice cream, margarine, milk (cow, goat, sheep), soft cheese, including cottage cheese and ricotta, yogurt
- legumes such as baked beans, chickpeas, lentils, kidney beans
- sweeteners such as fructose, high fructose corn syrup, isomalt, maltitol, mannitol, sorbitol, xylitol
- vegetables such as artichokes, asparagus, avocado, beets, broccoli, brussel sprouts, cabbage, cauliflower, garlic (with large consumption), fennel, leeks, mushrooms, okra, onions, peas, radiccio lettuce, scallions (white parts), shallots, sugar snap peas, snow peas
Simethicone (e.g., Gas-X, Mylanta Gas, Phazyme) is a foaming agent active in the stomach so that gas is more easily belched up. However, simethicone has no effect on intestinal gas. Simethicone preparations are widely used but have not proven clinical benefit.
Beano™, an alpha-galactosidase over-the-counter agent may reduce gas production in subjects taking non-digestable fibers, but its clinical value is questionable. Beano comes in liquid or tablet form. Beano has no effect on gas caused by lactose or fiber. Heat degrades the enzyme in Beano so it cannot be added to food while it is being cooked. Since Beano is made from an enzyme (alpha-galactosidase) extracted from a food-grade mold, patients with allergies to molds may react to Beano. Those with galactosemia (an inherited disorder characterized by the inability to metabolize galactose) should not use Beano.
The enzyme lactase, which aids with lactose digestion, is available in liquid and tablet form without a prescription (e.g., Dairy Ease, Lactaid). Adding a few drops of liquid lactase to milk before drinking it or chewing lactase tablets just before eating helps digest foods that contain lactose. Also, lactose-reduced milk and other products are available at many grocery stores.
If bacterial overgrowth or an altered flora are strongly suspected (best confirmed by breath-testing), a two-week trial of an antibiotic treatment may be helpful (i.e. Xifaxan® – rifaximin, a nonabsorbable antibiotic).
Probiotics such as ALIGN® – bifidobacterium infantis have been tried with varied success.
Smaller more frequent meals, less fatty foods and a trial of digestive pancreatic enzymes may all be of value.
Summary
In summary gas and bloating are difficult to treat symptoms which require vigilance and close cooperation between patients and providers in hope of partial or complete symptom relief. I typically approach this in a stepwise fashion. Laboratory testing will be used to screen for inflammation and celiac disease, while a trial of ALIGN may be initiated. If warning signs such as weight loss are present, aggressive work-up is immediately warranted. Otherwise a more conservative approach can be tried. Breath testing for lactose intolerance and work-up for small bowel overgrowth should be done. Dietary modifications will always be stressed and the FODMAP diet be reviewed.
You might find more info regarding functional gastrointestinal and motility disorders at the IFFGD website.
Gastroparesis
The current guidelines as published by the American College of Gastroenterology (ACG) on the management of gastroparesis are summarized below.
Gastroparesis is a common disorder that produces symptoms of gastric retention in the absence of physical obstruction. Patients report nausea, vomiting, early satiety, and fullness. These symptoms may be intermittent or continuous. Less recognized symptoms include pain and bloating. Gastroparesis may cause diminished caloric intake as well as vitamin (A, B6, C, K) and mineral (iron, potassium, zinc) deficiencies. Management of gastroparesis includes correction of these nutritional deficiencies, relief of symptoms of gastric emptying and, in diabetics, improvement of glycemic control. If oral intake is not adequate, enteral nutrition via jejunostomy tube needs to be considered. Medical therapy uses prokinetic and antiemetic drugs (i.e. metoclopramide, domperidone, erythromycin), as well as centrally acting antidepressants (used as symptom modulators). Gastric electrical stimulation (GES) may relieve symptoms, such as vomiting. Surgical approaches include a venting gastrostomy and feeding jejunostomy. Partial gastrectomy and pyloroplasty should be used only in carefully selected patients.
DEFINITION
- The diagnosis of gastroparesis is based on the combination of symptoms, absence of gastric outlet obstruction or gastric ulceration, and delay in gastric emptying.
- Accelerated gastric emptying and functional dyspepsia can present with similar symptoms to those of gastroparesis; documentation of delayed gastric emptying is recommended before selecting therapy with prokinetic agents or gastric electrical stimulation (GES).
CAUSE OF GASTROPARESIS
- Patients should be screened for diabetes mellitus, thyroid dysfunction, neurological disease, a history of prior gastric or bariatric surgery, and autoimmune disorders.
- A prodrome suggesting viral illness may lead to gastroparesis (postviral gastroparesis).
- Uncontrolled ( > 200 mg/dl) glucose levels may aggravate symptoms of gastroparesis and delay gastric emptying. Optimization of glycemic control may improve symptoms of delayed gastric emptying.
- Medication-induced delay in gastric emptying (i.e. from narcotic and anticholinergic agents) should be considered.
- Gastroparesis can be associated with gastroesophageal reflux disease (GERD) and should be considered in patients with refractory GERD.
DIAGNOSIS
- Delay in gastric emptying is required for the diagnosis of gastroparesis. Scintigraphic gastric emptying of solids is the standard for a diagnosis of gastroparesis. The most reliable method is gastric retention of solids at 4 h measured by scintigraphy. Medications that affect gastric emptying should be stopped at least 48 h before diagnostic testing and patients with diabetes should have blood glucose <275mg/d before starting the gastric emptying test.
DIFFERENTIAL DIAGNOSIS
- The presence of rumination syndrome, cyclic vomiting syndrome (CVS) or eating disorders (anorexia nervosa, bulimia) should be considered.
- Chronic cannabinoid agent usage may cause a CVS like syndrome.
MANAGEMENT
I. NUTRITIONAL THERAPY
- Management includes restoration of fluids and electrolytes, nutritional support and optimization of glycemic control in diabetics.
- Oral intake is preferable for nutrition and hydration.
- Patients should receive dietician counseling regarding frequent small low fat, low fiber meals.
- Enteral nasoenteric or jejunostomy tube feeding should be pursued, if oral intake is insufficient, especially if unintentional weight loss of 10% during a period of 3–6 months or repeated hospitalizations occur.
- Enteral postpyloric feeding is preferable to gastric feeding and preferable to parenteral nutrition.
II. GLYCEMIC CONTROL
- Good glycemic control should be the goal as hyperglycemia inhibits gastric emptying.
- Pramlintide and GLP-1 analogs may delay gastric emptying in diabetics. Cessation of these treatments should be considered before initiation of therapy for gastroparesis.
III. PHARMACOLOGIC THERAPY
- Prokinetic therapy should be used to improve gastric emptying and gastroparesis symptoms.
- Metoclopramide is the first line therapy and should be administered at the lowest effective dose (in a liquid formation to facilitate absorption). The risk of tardive dyskinesia is estimated to be <1%. Discontinue therapy if involuntary movements develop.
- Domperidone can be prescribed with investigational new drug (IND) clearance from the Food and Drug Administration (FDA). It appears as effective as metoclopramide without causing central nervous system side effects. Domperidone may prolong the corrected QT interval on electrocardiogram; a baseline electrocardiogram is recommended and treatment withheld if the corrected QT is >470ms in male and 450ms in female patients. Follow-up electrocardiogram on treatment with domperidone is advised. Erythromycin improves gastric emptying. Erythromycin should be given iv in hospitalized patients. Oral treatment with erythromycin improves gastric emptying, however, effectiveness of oral therapy is limited by tachyphylaxis.
- Treatment with antiemetic agents will improve nausea and vomiting but not improve gastric emptying.
- Tricyclic antidepressants (TCA) can be considered for refractory nausea and vomiting in gastroparesis but will not result in improved gastric emptying and may even worsen gastric emptying.
IV. INTRAPYLORIC BOTULINUM TOXIN INJECTION
- Intrapyloric botulinum toxin injection is not recommended.
V. GASTRIC ELECTRICAL STIMULATION
- GES may be considered for compassionate treatment in patients with refractory symptoms, particularly nausea and vomiting. Symptom severity and gastric emptying have been shown to improve in patients with diabetic gastroparesis (DG), but not in idiopathic (IG) or postsurgical gastroparesis (PSG).
VI. SURGICAL TREATMENTS: VENTING GASTROSTOMY, GASTROJEUNOSTOMY, PYLOROPLASTY, AND GASTRECTOMY
- A venting gastrostomy and feeding jejunostomy may be performed for symptom relief.
- Completion gastrectomy could be considered in patients with PSG who remain markedly symptomatic and fail medical therapy.
- Surgical pyloroplasty or gastrojejunosotomy have been performed for treatment for refractory gastroparesis, but further studies are needed before advocating this treatment.
- Partial gastrectomy and pyloroplasty should only be used in carefully selected patients.
VII. ALTERNATIVE MEDICINES
- Acupuncture has been associated with improved rates of gastric emptying and reduction of symptoms.
UG’s addendum to these guidelines: Some of our patients have also responded well to Iberogast, an OTC herbal preparation.
Utah Gastroenterology Blog 