Characteristics of Immune Checkpoint Inhibitor-Associated Gastritis: Report from a Major Tertiary Care Center.

BACKGROUND: Immune checkpoint inhibitors (ICIs) have increased our ability to treat an ever-expanding number of cancers. We describe a case series of 25 patients who were diagnosed with gastritis following ICI therapy. MATERIALS AND METHODS: This was a retrospective study involving 1712 patients treated for malignancy with immunotherapy at Cleveland Clinic from January 2011 to June 2019 (IRB 18-1225). We searched electronic medical records using ICD-10 codes for gastritis diagnosis confirmed on endoscopy and histology within 3 months of ICI therapy. Patients with upper gastrointestinal tract malignancy or documented Helicobacter pylori-associated gastritis were excluded. RESULTS: Twenty-five patients were found to meet the criteria for diagnosis of gastritis. Of these 25 patients, most common malignancies were non-small cell lung cancer (52%) and melanoma (24%). Median number of infusions preceding symptoms was 4 (1-30) and time to symptom onset 2 (0.5-12) weeks after last infusion. Symptoms experienced were nausea (80%), vomiting (52%), abdominal pain (72%), and melena (44%). Common endoscopic findings were erythema (88%), edema (52%), and friability (48%). The most common diagnosis of pathology was chronic active gastritis in 24% of patients. Ninety-six percent received acid suppression treatment and 36% of patients also received steroids with an initial median dose of prednisone 75 (20-80) mg. Within 2 months, 64% had documented complete resolution of symptoms and 52% were able to resume immunotherapy. CONCLUSION: Patients presenting with nausea, vomiting, abdominal pain, or melena following immunotherapy should be assessed for gastritis and if other causes are excluded, may require treatment as consideration for complication of immunotherapy.

Upper Gastrointestinal Bleeding.

Upper gastrointestinal (GI) bleeding is a common reason for hospital admission in older adult patients and carries a high morbidity and mortality if not properly managed. Risk factors include advanced age, Helicobacter pylori infection, medication use, smoking, and history of liver disease. Patients with known or suspected liver disease and suspected variceal bleeding should also receive antibiotics and somatostatin analogues. Risk stratification scores should be used to determine patients at highest risk for further decompensation. Upper endoscopy is both a diagnostic and therapeutic tool used in the management of upper GI bleeding. Endoscopy should be performed within 24 hours of presentation after appropriate resuscitation. Management of anticoagulation in upper GI bleeding largely depends on the indication for anticoagulation, the risk of continued bleeding with continuing the medication, and the risk of thrombosis with discontinuing the medication. A multidisciplinary approach to the decision of anticoagulation continuation is preferred when possible.

Renal failure caused by a partly calcified aortic aneurysm in a patient with dabigatran therapy: A case report.

RATIONALE: Abdominal aortic aneurysms (AAAs) are mostly asymptomatic. If aortic aneurysms become symptomatic, complications include peripheral embolization, acute aortic occlusion, and aortic rupture. However, there are also unusual complications caused by aortic aneurysms. PATIENT CONCERNS: An 87-old male with dabigatran therapy presented with newly developed melena and acute renal failure. Radiological imaging revealed an AAA with thrombotic and calcified deposits which affected the renal arteries. DIAGNOSES: Gastrointestinal bleeding and hypercoagulation caused by renal failure which was triggered in turn due to an AAA. INTERVENTIONS: Adapted antihypertensive therapy and initiation of simvastatin 40mg once daily as well as antiplatelet therapy with aspirin 50 mg once daily due to patient's refusal of any aneurysm intervention. OUTCOME: Neither bleeding event nor aneurysm rupture occurred with the adapted antihypertensive therapy, simvastatin and aspirin. LESSONS: Nonruptured AAAs can cause rare, unusual, and even life-threatening complications depending on their size and anatomical position.

Severe Chikungunya infection in Northern Mozambique: a case report.

BACKGROUND: Although Chikungunya virus has rapidly expanded to several countries in sub-Saharan Africa, little attention has been paid to its control and management. Until recently, Chikungunya has been regarded as a benign and self-limiting disease. In this report we describe the first case of severe Chikungunya disease in an adult patient in Pemba, Mozambique. CASE PRESENTATION: A previously healthy 40 year old male of Makonde ethnicity with no known past medical history and resident in Pemba for the past 11 years presented with a severe febrile illness. Despite administration of broad spectrum intravenous antibiotics the patient rapidly deteriorated and became comatose while developing anaemia, thrombocytopenia and later, melaena. Laboratory testing revealed IgM antibodies against Chikungunya virus. Malaria tests were consistently negative. CONCLUSIONS: This report suggests that Chikungunya might cause unsuspected severe disease in febrile patients in Mozambique and provides insights for the improvement of national protocols for management of febrile patients in Mozambique. We recommend that clinicians should consider Chikungunya in the differential diagnosis of febrile illness in locations where Aedes aegypti mosquitos are abundant.

Talidomida en dosis altas para la hemorragia digestiva oscura grave idiopática en una paciente de alto riesgo trombótico / High-dose thalidomide for severe idiopathic obscure gastrointestinal bleeding in a patient at high-thrombotic risk

Se presenta el caso de una mujer de 81 años con accidentes vasculares cerebrales (ACV) recurrentes con doble antiagregación y hemorragia digestiva de origen oscuro. No se encontró el origen del sangrado con cápsula endoscópica, enteroscopia de doble balón, laparotomía exploradora y enteroscopia intraoperatoria bidireccional desde boca a ano. La paciente requirió la transfusión de 117 concentrados de hematíes durante 2 años pese a suspensión de la medicación antiagregante y tratamiento con análogos de la somatostatina. Por ello, se inició terapia con dosis crecientes de talidomida, hasta 300mg, asociadas a profilaxis tromboembólica durante 3 meses, sin respuesta. Al suspender la heparina, la hemorragia se controló durante 3 meses, pero se retiró la talidomida por efectos secundarios. Dado que la hemorragia recidivó al mes de la suspensión, se realizó un segundo ciclo de 3 meses de tratamiento con talidomida. Durante un año de seguimiento, la paciente no ha precisado transfusión de hemoderivados (AU)

We report the challenging case of an 81-year-old woman on dual antiplatelet therapy with recurrent strokes, who presented with severe obscure gastrointestinal bleeding. A thorough diagnostic work-up, including capsule endoscopy, double balloon enteroscopy, arteriography, exploratory laparotomy and mouth-to-anus intraoperative enteroscopy, failed to reveal the source of the bleeding. During a 2-year period, the patient required 117 packed red blood cell units, despite withdrawal of antiplatelet drugs and empirical therapy with high-dose somatostatin analogues. The patient was administered an increasing dosage of thalidomide, up to 300mg/day, with thromboembolism prophylaxis for 3 months, with no clinical response. The bleeding stopped for 3 months after heparin was discontinued, but thalidomide had to be withdrawn owing to adverse effects. Since bleeding recurred a month later, the patient underwent another 3-month course of thalidomide. The patient has not required further blood transfusion after a 1-year follow-up (AU)

In vivo endoscopic imaging of ancylostomiasis-induced gastrointestinal bleeding: clinical and biological profiles.

Little data are available regarding the association of ancylostomiasis with overt gastrointestinal bleeding. This 6-year retrospective study describes the clinical and biological profiles of unexpectedly identified ancylostomiasis in a 4-month-old baby and four adults; they presented with melena and were referred for urgent diagnostic gastrointestinal endoscopy, which confirmed numerous small intestine injuries with surrounding blood pools caused by Ancylostoma duodenale worms. Gastric erosions were also encountered in one patient. Uniquely, worm biological activities were recorded live in vivo, including mucosal invasion through a vigorous, rapid piercing process, repeated bloodsucking habits, and gut appearance during the stages of feeding, digestion, and excretion in male and female worms. In conclusion, ancylostomiasis-induced melena may occur in all ages from infants to the elderly. Worm bloodfeeding occurs after quick mucosal piercing, with blood loss being aggravated by a repeated feeding behavior. After treatment is started, bleeding stops rapidly in response to anthelmintic therapy.

Octreótida en el sangrado por angiodisplasias intestinales / No disponible

No disponible

Thalidomide as treatment for digestive tract angiodysplasias.

An 80-year-old man with von Willebrand's disease was admitted with severe melaena. Despite suppletion with von Willebrand concentrate he continued to be dependent on blood transfusions. Endoscopic examination did not show a bleeding focus. Video capsule endoscopy showed active bleeding from angiodysplasias in the proximal section of the small intestine. Ultimately, treatment with thalidomide was initiated at a dose of 100 mg/day. Soon after starting treatment his stools became normal and his haemoglobin level stabilised. No bleeding problems occurred for 11 months, after which the thalidomide treatment was stopped because of the potential side effects. Two months later he again developed melaena and treatment with thalidomide was restarted with a successful outcome. Trying to lower the dose to 50 mg resulted in rebleeding after three months with stabilisation after increasing the dose to 100 mg again. Monotherapy with thalidomide improves the clinical picture but may not be sufficient in the long term. Additional therapy, such as argon plasma coagulation or the use of the novel drug lenalidomide, might be necessary.

Phase III study of pentosanpolysulfate (PPS) in treatment of gastrointestinal tract sequelae of radiotherapy.

OBJECTIVES: To evaluate the effectiveness of pentosanpolysulfate (PPS) in the treatment of gastrointestinal tract sequelae of radiotherapy. METHODS: Eligible patients were those with grade 1 to 3 radiation related proctitis, diarrhea and/or melena. At least 4 weeks had to elapse since the completion of the radiotherapy course. Patients with bleeding diathesis or ulcers, and patients receiving anticoagulants or chemotherapy were excluded. Stratification criteria included the type of sequelae (proctitis, diarrhea, melena), the severity grade and the onset (<3 months post-RT, >3 months post-RT). Patients were randomized to one of the following arms: 100 mg PPS 3 times per day (300 mg/day), 200 mg PPS 3 times per day (600 mg/day), or placebo 3 times per day. If there was no improvement in symptoms after 2 months, the protocol treatment was discontinued. If the symptoms improved or resolved, the protocol treatment was continued for additional 4 months. Patients under treatment were evaluated monthly, than every 2 to 3 months for the next 18 months. A symptom assessment questionnaire was used to measure quality of life endpoints. RESULTS: From June 1999 to March 2001 180 patients were accessioned from 34 institutions. A total of 168 were analyzable. Neither the best observed response within 3 months for the entire population, nor the response rate within sequelae category or the quality of life measures differed significantly between the 3 arms of the study. CONCLUSION: Administration of PPS has not been associated with an improvement in the clinical course of radiation related morbidity of the gastrointestinal tract.

Flavonoids to reduce bleeding and pain after stapled hemorrhoidopexy: a randomized controlled trial.

INTRODUCTION: Control of postoperative symptoms is of paramount importance in ambulatory surgery. This trial was conducted to evaluate whether a micronized purified flavonoid fraction (MPFF) (Detralex((R))) reduces postoperative bleeding, pain and consumption of analgesics after ambulatory stapled hemorrhoidopexy, as reported in trials after classic hemorrhoidectomy. Phlebotropic activity, protective effect on the capillaries and anti-inflammatory properties of this drug have been reported in several studies. METHODS: Sixty-three patients with third-degree hemorrhoids had ambulatory stapled hemorrhoidopexy under spinal anesthesia in the period of one year. The patients were randomized, with 30 receiving Detralex 500 mg (2 tablets 3 times daily for 5 days after the operation) and 33 forming the control group. The patients were asked to daily self-assess the presence of blood on defecation, degree of pain and consumption of analgesics for the first week after the operation. RESULTS: There was no significant difference between the two groups in duration of presence of blood, degree of pain or analgesics requirement. No major complications, such as bleeding requiring transfusion or hospitalization, sepsis, anal stenosis or urgent defecation, were noted in the follow-up period. There were no side effects from Detralex treatment. DISCUSSION: In our study we could not demonstrate any positive effect of prescribing flavonoids after stapler hemorrhoidopexy. This procedure may not be sufficiently aggressive and is associated with too few postoperative complications to show any protective influence of flavonoids.

Myocardial infarction following recombinant activated factor VII in a patient with type 2A von Willebrand disease.

We describe a 50-year-old man with von Willebrand disease type 2A who suffers from angiodysplasia and has required many transfusions for gastro-intestinal haemorrhage. Various investigative modalities have not demonstrated a single source for this. Following a case report of successful use of recombinant activated factor VII (NovoSeven; Novo Nordisk, Copenhagen, Denmark), the patient was treated with it but suffered a large myocardial infarct. As the patient has risk factors for atherosclerotic disease, we presume the recombinant activated factor VII promoted coagulation at a pre-existing atherosclerotic lesion.

Two cases of colonic tuberculosis presenting with massive melena.

The clinical symptoms of colonic tuberculosis are variable, among which massive melena is extremely rare. Herein, we report two cases of colonic tuberculosis representing with massive melena, both of whom never had active pulmonary tuberculosis. The first case was a 55-year-old woman. Although her emergency colonoscopic setting suggested colonic tuberculosis, no evidence of tuberculosis could be found at that time. We performed a therapeutic trial and observed a drastic regression of the initial changes with 4-week treatment using antituberculous agents. The second case was a 37-year-old man. His emergency colonoscopy showed lesions mimicking colon carcinoma. However, the histological examinations did not indicate malignancy. The polymerase chain reaction of colonic biopsy specimen was positive for Mycobacterium tuberculosis. Similar to the first case, a significant improvement of the initial lesions was observed after 4-week treatment using antituberculous agents. Collectively, although the massive melena is a rare manifestation, tuberculosis of the colon should be suspected in the patients with such symptom.

[Antibodies against human recombinant erythropoietin: an unusual cause of erythropoietin resistance]. / Anticorps anti-érythropoïétine humaine recombinante: une cause exceptionnelle de résistance à l'érythropoïétine.

In a 70 year old man with primary glomerulonephritis, severe anemia occurred after 4 years on hemodialysis and rHu-EPO. The usual mechanisms of EPO-resistance were excluded. A bone marrow sample showed red all aplasia. No circulating EPO could be detected; the serum inhibited the growth of erythroid precursors in bone marrow cultures. Immunoprecipitation identified an IgG anti-EPO, still active against deglycosylated EPO, i.e. directed against the peptidic matrix. Its high neutralising capacity and the absence of any immune abnormality rule out an auto-antibody. Anti-rHu EPO immunisation is a very rare occurrence, made severe by transfusion-dependence and the risk of hemosiderosis. An immuno-modulating treatment can therefore be justified.

Thrombocytopenia associated with octreotide.

A 42-year-old woman with a history of hepatitis C-induced cirrhosis, gastrointestinal bleeding, and alcohol abuse presented to the hospital with hematemesis and melena. Based on our previous experience, octreotide (Sandostatin) therapy was started at 50 mg/hr and continued for 5 days. Platelet count on admission (122 x 10(9)/L) dropped immediately after octreotide therapy was started; upon discontinuation, platelet count began trending up from 72 x 10(9)/L. However, octreotide was not suspected at this point as the cause of thrombocytopenia. In a subsequent admission, octreotide was again administered with a resultant prompt decrease in platelet count. To our knowledge, this is only the second case report of octreotide-induced thrombocytopenia, and the first case of this adverse effect demonstrated by inadvertent rechallenge.

Massive gastrointestinal hemorrhage in systemic lupus erythematosus: successful treatment with corticosteroid pulse therapy.

Although mesenteric vasculitis due to systemic lupus erythematosus (SLE) is relatively uncommon, it is the most dangerous manifestation associated with high mortality. We describe the case of a SLE patient with life-threatening gastrointestinal hemorrhage due to mesenteric vasculitis in whom methylprednisolone pulse therapy was quite effective in controlling the hemorrhage and resulted in a satisfactory long term outcome. A 47-yr-old woman presenting with high fever, rash, and melena was diagnosed with SLE from positive antinuclear antibodies, anti-dsDNA, and low complement titers. Although fever and rash subsided with administration of prednisolone, massive hematemesis appeared with melena. Endoscopy demonstrated bleeding ulceration of the antrum, which was intractable despite intensive antiulcer therapy and transfusion. Surgical exploration revealed ileal penetration, and multiple bleeding ulcerations were observed over the resected ileum as well as the antral ulceration. However, bleeding persisted after surgery and surgical findings prompted us to select methylprednisolone pulse. Hemorrhage responded promptly to the therapy, and the patient has remained well since then for >10 yr. Our report indicates that corticosteroid pulse may serve as one of the therapeutic options for SLE with massive hemorrhage due to widespread mesenteric vasculitis.

Octreotide compared with placebo in a treatment strategy for early rebleeding in cirrhosis. A double blind, randomized pragmatic trial.

beta-Blockers and sclerotherapy prevent long-term upper digestive rebleeding in cirrhosis but they seem ineffective for early rebleeding. We compared octreotide with a placebo for the prevention of early rebleeding in cirrhotic patients. After control of acute upper digestive bleeding, 262 consecutive cirrhotic patients were randomized to octreotide 100 microgram subcutaneously three times a day for 15 days (n = 131) or to the placebo (n = 131), in a double blind pragmatic trial in which beta-blockers and/or sclerotherapy were allowed together with the experimental treatment. Separate randomization and analysis were performed according to whether patients were eligible for beta-blockers and/or sclerotherapy (101 placebo, 97 octreotide) or not (30 placebo, 34 octreotide). Rebleeding within 15 days was the primary measure of treatment efficacy; 6-week rebleeding rate was also assessed as a secondary measure. Fifteen-day cumulative proportions of patients rebleeding were 28% in the placebo group and 24% in the octreotide group (P = .40); corresponding figures among the 198 patients eligible to beta-blockers and/or sclerotherapy were 26% and 16% (P = .05) and among the 64 not eligible for these treatments 33% and 49% (P = .29). Among patients eligible to beta-blockers and/or sclerotherapy, a significant reduction of rebleeding episodes (35 vs. 18, P = .03), blood transfusions (75 vs. 50, P = .04), and days of stay in hospital (1,544 vs. 1,190, P = .0001) was also found in the octreotide group: this beneficial effect was confirmed 6 weeks after randomization. Mortality was not affected by octreotide in either group of patients. It is suggested that octreotide may reduce the risk of early rebleeding in cirrhotic patients treated with beta-blockers and/or sclerotherapy after control of acute upper digestive bleeding. Further studies are needed to confirm this result.

[Gastric vascular ectasia (GAVE) or watermelon stomach (WS): infrequent cause of anemia]. / Ectasia vascular del antro (EVA) ó Watermelon Stomach (WS). Poco frecuente causa de anemia.

The gastric vascular ectasia (GAVE) or watermelon stomach (WS) is an unfrequent cause of anemia or evident upper gastrointestinal bleeding in elderly patients. We presented five female patients, average age 79 years, 4 of them with a long evolution anemia and one with melena. Three of them showed a typical WS endoscopy, 2 of them with diffuse patent. All 5 cases with positive pathologic findings: vascular ectasia, fibrin thrombi and fibromuscular hyperplasia. The endoscopic biopsy is as accurate as the study of the antrectomy piece. None of them had portal hypertension although the GAVE would be different entity from the cirrhotic vascular gastropathy. The treatment consisted in monopolar electrocoagulation of the lesions after the failure with the medical treatment in one case, corticosteroid and ferrous therapies in the three cases and one of them didn't require treatment up to now.