الارتداد المعدي المريئي - الدكتور / وليد يوسف فرح استشاري امراض الجهاز الهضمي والكبد

مقدمة

المريء هو أنبوب عضلي ضيق يبلغ طوله حوالي 40 سنتيمتر . ويبدأ بعد اللسان وينتهي في المعدة يتألف من ثلاث طبقات ليفية من الخارج وعضلية في الوسط وغشاء مخاطي من الداخل .
التعريف
الارتداد المريئي هو أعراض مزمنة أو تخريب لمخاطية المريء ينتج عن رجوع زائد وغير طبيعي لحامض المعدة إلى المريء وهذا ما يطلق عليه الارتداد ، ويحدث نتيجة قصور في الوظيفة العضلية للمريء أو فشل في وسائل الحماية الأخرى.

الوبائيات
يعتبر الارتداد المريئي مرض شائع جداً يصيب 20 -40 % من الناس . وقد زادت نسبة حدوثه خلال العقود الماضية ويحدث الارتداد بالتساوي في كلا الجنسين أما التهاب المريء ( الناتج عن الارتداد ) فيحدث في الذكور ضعف الإناث كما يحدث الارتداد في كافة الأعمار وتزداد نسبة حدوثه بعد سن الأربعين .
آلية حدوث الارتداد المريئي
في الواقع إن البنية الأهم في الحماية من حدوث الارتداد المريئي هي طبقة عضلية في أسفل المريء عند اتصاله بالمعدة تسمى مصرة المريء السفلي حيث تفتح بعد البلع ليتمكن الطعام من الدخول إلى المعدة وتنغلق مباشرة بعد ذلك لمنع حدوث أي ارتداد لمحتويات المعدة ( بما فيها الحامض ) إلى المريء وتحافظ على وضعية الإغلاق حتى يتم البلع مرة أخرى .

الأعراض السريرية
• الحرقة : إحساس بالحرقة خلف عظمة القص ويحدث هذا الإحساس بإرتداد الحامض المعدي الذي تزيد كميته بعد تناول الوجبات وفي وضعية الاستلقاء .
• عسر البلع
• البلع المؤلم
• التجشوء
• التظاهرات خارج المريء وهى الأعراض التي تحدث في مناطق خارج المريء وتلاحظ كثيراً في المرضى المحولين من عيادات أخرى للإشتباه بوجود الارتداد المريئي لديهم ، وأ÷م هذه الأعراض .
- ألم الصدر غير المفسر
حيث يحضر المرضى إلى عيادات أمراض القلب إثر معاناتهم من ألم في الصدر والاشتباه بوجود أمراض نقص التروية القلبية من ذبحة صدرية وأحتشاء قلبي ولكن بعد إجراء جميع الفحوصات يتبين عدم وجود أي علامات لذلك وهنا يتم الأشتباه بوجود الارتداد المعدي المريئي كمسبب لألم الصدر .
- تظاهرات رئوية
هناك العديد من الأمراض الرئوية قد تظهر بسبب وجود الارتداد المريئي وأهمها
• الربو القصبي
• التهاب القصبات المزمن
• ذات الرئة الإستنشاقية
• انقطاع التنفس أثناء النوم
• انخماص الرئة
• التليف الرئوي

- تظاهرات أذنية
قد يراجع المرضى اختصاصي الأنف والأذن والحنجرة إثر شكواهم من أحد الأعراض التالية :
• السعال
• ألم الحلق
• بحة الصوت
• التهاب الجيوب الأنفية المزمن
• التهاب البلعوم الخلفي
• إحساس بوجود جسم غريب في الحلق

التشخيص
القصة المرضية مهمة جداً في تشخيص الارتداد المعدي المريئي ، وهناك أسئلة ذات أهمية تشخيصية عالية يوجهها الطبيب لمريضة وهى:
1- هل تعاني من إحساس عدم الارتياح منتشر للأعلى خلف القص ؟
2- هل يصاحب هذا الإحساس حرقة بأعلى البطن ؟
3- هل استعمال مضادات الحموضة تخفف الأعراض ؟
4- هل حدثت الأعراض لمدة أكثر من 4 أيام خلال الأسبوع المنصرم ؟
وقد وجد أن 85% من المرضى يجيبون بنعم على جميع الأسئلة .
وقد يلجأ الطبيب لإجراء الفحوصات الشعاعية ونعني هنا الوجبة الباريتية وهي مفيدة في المرضى الذين يعانون من عسر البلع حيث يمكن أن توضح مكان وجود التضيق إن وجد كما يمكن الاستدلال على وجود وشكل الفتق الحجابي لإذا كان مصاحباً
وفي كثير من الأحيان يُّجرى للمريض التنظير الهضمي العلوي بالمنظار حيث يتم التأكد من وجود التهاب المريء وتحديد درجة الالتهاب وإمكانية وجود داء باريت وينفي وجود أمراض أخرى مشابهة من ناحية الأعراض مثل القرحة الهضمية . وفي أكثر من نصف المرضى يكون التنظير طبيعياً بالرغم من وجود الارتداد .
ومن الفحوصات التي قد يلجأ إليها الطبيب مراقبة إفراز الحامض المعدي لمدة 24 ساعة . ويستطب إجراء هذا الفحص في المرضى ذوي التنظير الطبيعي ويعانون من أعراض الارتداد ولا يستجيبو للعلاج أو الذين يشكون من ألم صدر غير نوعي ومظاهر خارج المريء ( ربو ، بحة ، سعال مزمن ) ، وكذلك في المرضى ذوي التنظير المرضي ولا يستجيبو للعلاج أو المرضى الذين سيخضعوا للعلاج الجراحي .

التشخيص التفريقي
يمكن أن يختلط تشخيص الارتداد المريئي بالكثير من الأمراض التي تتشابه معه في الصورة السريرية نذكر منها :
• التهاب المعدة
• التهاب المريء الميكروبي
• التهاب المريء بالأدوية
• القرحة الهضمية
• عسر الهضم
• أمراض القنوات الصفراوية
• أمراض الشرايين التاجية القلبية
• اضطرابات المريء الحركية

المضاعفات
قد يترافق الارتداد المريئي بالعديد من المضاعفات ومنها
• التضيق
• داء باريت
• السرطان الغدي للمريء

العلاج
يهدف العلاج إلى إراحة المريض من الأعراض وشفاء التهاب المريء بالإضافة إلى تجنب حدوث المضاعفات ؟
والخطوة الأولى والأهم في علاج التهاب المريء تقع على كاهل المريض ذاته وذلك بإتباع النصائح والإرشادات التالية :
رفع رأس السرير من جهة الرأس وإتباع حمية صارمة لإنقاص الوزن وتناول وجبات خفيفة بفترات متقاربة بدلاً من الوجبات العادية والأهم عدم تناول الطعام قبل الذهاب إلى النوم بساعتين على الأقل .
كما يتوجب على المريض الامتناع عن التدخين والكحول والنعناع والشوكولاته والأطعمة الدسمة .
أما العلاج الدوائي فالهدف الأساسي منه هو إراحة المريض من الأعراض التي يشكو منها والحفاظ على درجة حموضة المعدة بمستوى 4 أو أكثر .
وكانت مضادات الحموضة حجر الزاوية في العلاج حتى السبعينات من القرن الماضي حيث تم استحضار مضادات مستقبلات الهستامين حيث بدأ استعمال السيميتيدين وحالياً يتوفر علاجات أخرى ضمن هذه المجموعة تعطي وظيفة ألإضل ومضاعفات أقل .
وفي عام 1988 بدأ استعمال مضادات البروتون والعلاج الأقدم في هذه المجموعة هو الأميبرازول وتلا ذلك استحضار علاجات أخرى ضمن هذه المجموعة والاحدث عقار إيسوميبرازول في عام 2000 م .
وتعطى هذه الأدوية بمعدل مرة إلى مرتين يومياً وقد يحتاج المرضى للمواظبة على العلاج لفترات طويلة . وفي بعض الحالات قد يلجأ الطبيب للتدخل الجراحي بإجراء عمليات الهدف منها منع حدوث ارتداد حامض المعدة إلى المريء ولا يتسع المقام هنا لتفصيلها .

Early endoscopic follow-up nets dysplasia in 9.5% of Barrett’s

CHICAGO (FRONTLINE MEDICAL NEWS) – Early endoscopic follow-up within 24 months detected dysplasia in nearly one in 10 patients with nondysplastic or low-grade Barrett’s esophagus in a retrospective study at the Mayo Clinic. Initial endoscopy missed four cases of high-grade dysplasia or esophageal adenocarcinoma (1.9%) and 16 cases of low-grade dysplasia (7.6%) for an overall miss-rate of 9.5%. Patients on proton pump inhibitors were less likely to have dysplasia missed than were those off PPIs (20% vs. 52.6%, P = .008). Those with long- versus short-segment Barrett’s esophagus were more likely to have dysplasia overlooked (85% vs. 53.6%; P = .008; mean 6 mm vs. 4 mm; P = .006), Dr. Kavel Visrodia said at the annual Digestive Disease Week. Current American College of Gastroenterology (ACG) guidelines recommend early repeat esophagogastroduodenoscopy (EGD) to exclude the presence of missed dysplasia in newly diagnosed nondysplastic Barrett’s esophagus (BE), while the ACG and American Society for Gastrointestinal Endoscopy call for repeat EGD within 6 months for those with low-grade dysplasia. The yield for repeat EGD has not been established, and only one study exists in the literature, said Dr. Visrodia of the department of medicine, Mayo Clinic, Rochester, Minn. That study (Dis. Esophagus 2012 Sept. 28. [doi:10.1111/j.1442-2050.2012.01431.x]) showed a miss-rate of 8.2% among 146 patients with newly diagnosed nondysplastic BE. Long-segment BE was the only significant predictor of dysplasia on follow-up (odds ratio, 9.18; P = .008). The cohort was relatively small and had no long-term follow-up, and with an interval to follow-up of 36 months, “it’s possible that some of these were actually incident cases of dysplasia and not prevalent cases,” he said. To address these gaps, Dr. Visrodia and his colleagues identified 488 BE cases from 1977 to 2011 in the Rochester Epidemiology Project in Olmsted County, Minn. A total of 278 patients were excluded because of high-grade dysplasia (HGD) or esophageal cancer on index endoscopy or repeat endoscopy after 24 months, leaving 181 patients with nondysplastic BE and 29 with low-grade dysplasia (LGD). Repeat endoscopy within 24 months revealed 2 cases of HGD or cancer and 16 cases of LGD in the nondysplastic BE group, and 2 cases of HGD or cancer in the LGD group, Dr. Visrodia said. Three of the four HGD/cancer cases were in patients with long-segment BE, defined as at least 3 cm of columnar mucosa. Biopsies were insufficient in 63% of patients with missed dysplasia, compared with 55% in the group without missed dysplasia. Biopsies were considered adequate if the number of biopsies divided by the BE length was at least 2, indicating that samples were taken every 2 cm in accordance with guidelines. This risk factor is noteworthy, although the difference between groups was not statistically significant, possibly because of the small sample size, he said. Finally, after a median of 6.8 years of follow-up, 30 asymptomatic, prevalent HGDs or cancers were detected within 24 months, compared with 22 incident cases detected after 24 months. This suggests that “a greater number of high-grade dysplasias and cancers were detected up front rather than during long-term careful surveillance,” Dr. Visrodia said. During a discussion of the study, one attendee asked whether the results make a better case for aggressive ablation up front rather than for surveillance, while others expressed surprise at the high miss rate at an institution such as the Mayo Clinic. Dr. Visrodia replied that the results do give them pause, and suggested that tighter early endoscopic surveillance may be warranted, particularly in those with long-segment BE.

Infliximab monitoring during remission limits IBD flare-ups

Trough infliximab concentrations were measured in patients who were in clinical remission at about 1 year on maintenance therapy. When trough concentrations fell below 5 mcg/mL, patients got a dose increase. The goal was to prevent secondary loss of response due to recurrence of symptoms or antibody-mediated side effects, such as infusion reactions, Dr. Byron P. Vaughn explained at the annual Digestive Disease Week. In a retrospective, nonrandomized proof-of-concept study, 48 inflammatory bowel disease patients in remission on infliximab were proactively monitored, and 78 matched controls were conventionally managed. The infliximab discontinuation rate during up to 5 years of follow-up was 10% in the proactively monitored group and 31% in the controls. Nearly 90% of treatment discontinuations in the control group were caused by loss of response or development of acute infusion reactions; in contrast, no one in the proactively monitored group stopped infliximab for those reasons. “We think this is exciting information. We now recommend dose optimization to a trough level of at least 3 mcg/mL, and our current clinical practice is to target a range of 5-10 mcg/mL,” said Dr. Vaughn, of Beth Israel Deaconess Medical Center and Harvard University, Boston. Of course, the findings certainly need to be validated in a prospective study, he added. For about the first year of infliximab therapy, the treatment continuation curves were similar for the two groups. After 1 year, the curves separated and the benefit of proactive trough monitoring could be seen. The main reasons for stopping infliximab in the control group were a flare of symptoms (15 patients) and acute infusion reactions (6 patients). Neither of these events occurred in the proactively monitored patients. The reasons for treatment discontinuation in the proactively monitored group included drug-induced lupus (1 patient), psoriasis (1 patient), a delayed infusion reaction (1 patient), and a reason unrelated to the medication (1 patient). Three-quarters of study participants had Crohn’s disease, and the rest had ulcerative colitis. Other investigators have previously shown that an undetectable serum infliximab trough concentration in the setting of Crohn’s disease often heralds a loss of response. Dr. Vaughn emphasized that fully one in four patients had an undetectable trough level at the first measurement, and nearly two-thirds had levels below 5 mcg/mL. The infliximab dose was increased in those patients. Patients with a trough level of 5-10 mcg/mL received no change in their regimen, while those with a level of more than 10 mcg/mL on two occasions got either a dose reduction or an increase in the interval between doses if they were on 5 mg/kg. In gastroenterology, serum infliximab concentrations are typically measured when patients stop responding or have side effects. So the costs of proactive infliximab monitoring and dose escalation are going to be an impediment to widespread implementation of this strategy under many health plans, at least until there is confirmatory data, he said. Proactive trough concentration monitoring and dose titration are typical in recipients of solid organ transplants receiving cyclosporine, mycophenolate mofetil, and mTOR (mammalian target of rapamycin) inhibitors, and are often performed in sepsis patients receiving vancomycin and gentamicin. When asked how often he recommends proactive infliximab trough testing, Dr. Vaughn replied, “I think when people are in a steady state – they’re not ill and they’re not flaring – you could probably check once every 6 months or maybe once a year. After a few stable troughs, that could be enough unless there’s been a major change like a big weight change, a change in other medications, or an illness.”

Fecal transplant falls short in UC, but may not be the end

CHICAGO (FRONTLINE MEDICAL NEWS) – Results were negative from the first randomized placebo-controlled trial of fecal microbiota transplant in ulcerative colitis, but enthusiasm remains for this newly regulated and trendy therapy. “We need to get more data and we need to understand how better to use this approach, but I don’t think this study is telling us we should stop exploring. I still think it is an interesting avenue that we need to evaluate,” study author Dr. Paul Moayyedi said during a late-breaking abstract session at Digestive Disease Week. Part of the enthusiasm for what was described as “the new kid on the block for altering gut flora,” has been fueled by a roughly 90% success rate for fecal transplant in treating Clostridium difficile infection. Dr. Moayyedi also showcased a success story from the trial that “typifies a few patients in this study.” The patient had ulcerative colitis for almost 20 years that was unresponsive to steroids and 5-aminosalicylic acid for 2 years before the study and so severe it caused bloody diarrhea 10-20 times per day. No improvement was seen after 6 weeks of placebo therapy and his Mayo Clinic score was “about as bad as it can be” at 12. After crossing over to 6 weeks of open-label fecal microbiota transplantation (FMT), symptoms were much improved and his Mayo score dropped to 5. After 20 weeks, mucosa healed throughout the colon, his Mayo score reached 0, and he was “fine” on no medication. “What we’re finding is that 6 weeks is usually not enough and that if you continue longer, you can get remission in some patients,” said Dr. Moayyedi, the Richard Hunt-Astra Zeneca Chair in Gastroenterology, McMaster University, Hamilton, Ontario. He went on to say, “I’m a very big proponent of evidenced-based medicine, but cases like these make you think something must be going on in some patients, but we don’t have the funding to do the 500-patient trial you need to get that signal.” Dr. Moayyedi and his associates enrolled ambulatory patients with active ulcerative colitis, defined as a Mayo score of at least 4 and an endoscopic Mayo score of at least 1, who tested negative for the C. difficile gene. Patients could be on ulcerative colitis medications, if doses were stable for at least 12 weeks but had to be off antibiotics for 30 days. Patients were randomly assigned to receive a 50-mL retention enema containing fecal microbiota from an anonymous donor or water, once per week for 6 weeks. The primary outcome was remission of ulcerative colitis, defined as a Mayo score of 2 or less and an endoscopic Mayo score of 0 at week 7. Patients, clinicians, and investigators were blinded to therapy. The 31 FMT and 30 placebo patients were well matched at baseline, except for significantly more pancolitis in the FMT group (64% vs. 36%). Remission was achieved by seven FMT patients (23%) and two placebo patients (7%), which was not significantly different (P = .15), Dr. Moayyedi said. There also were no differences between the FMT and placebo groups in any of the secondary outcomes: 6-week Mayo score (6.36 vs. 6.30; P = .95), 6-week Inflammatory Bowel Disease Questionnaire (148.4 vs. 146.4; P = .85), and 6-week EQ-5D health questionnaire (61.0 vs. 66.2; P = .34). Based on these findings, the study is being stopped for futility, he said. There were no major adverse events, although the diagnosis changed to Crohn’s colitis for two patients given FMT and one on placebo. This was “much bigger than you’d expect,��� Dr. Moayyedi said. “We’re not sure why, and of course the worry is that FMT may change the phenotype, which would not be good.” If FMT is to succeed in ulcerative colitis, he suggested more data will be needed on the fecal microbiome and the best approach to administer FMT, including donor selection, timing, preparation, and duration of treatment. The group has not done an analysis of enema dwell time and response, and no signal was seen that FMT is more effective in left-sided disease. More detailed microbiome analyses of the patient highlighted during the talk, however, revealed the man had a “very diverse and unstable” microbiome at baseline that gradually became more stable, “with a loss of Ruminococcus that seems to be a feature of improvement and a movement toward the phenotype of the donor,” Dr. Moayyedi said. During a discussion of the results, some audience members expressed concern that FMT might change the phenotype, while others were more enthusiastic about the therapy. Dr. Scott Harris, a gastroenterologist and professor of medicine, Georgetown University Medical Center, Washington, said the trial was likely underpowered, and that by including patients with less severe disease, it may have been more difficult to see a treatment effect. Other trials have also shown that 6 weeks of therapy may not be enough for refractory patients. “I’m very optimistic, I wouldn’t stop at this point,” he said. Session cochair Dr. John M. Inadomi, professor of medicine and head of gastroenterology, University of Washington School of Medicine, Seattle, agreed that the length of treatment as well as the study’s use of anonymous donors could have affected results. One of the big questions is whether the donor feces actually grafted and thus affected the recipient. “If you use the wrong donor stool, if the stool didn’t graft, these kinds of things can obviously make a negative result, even if the concept is potentially fine,” he said in an interview. Last year, the Food and Drug Administration moved to require an investigational new drug permit to treat C. difficile with fecal microbiota, but changed course within weeks citing public pressure. While researchers are studying the potential to deliver feces via capsule, Dr. Moayyedi observed that some enthusiasts are offering Internet advice on how to mix your own FMT at home.