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.

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.

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.

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.

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.

[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.

Ectasia vascular del antro (EVA) o watermelon stomach (WS): poco frecuente causa de anemia / Gastric vascular ectasia (GAVE) or wartemelon stomach (WS): unfrequent cause of anemia

La ectasia vascular del antro (EVA) o watermelon stomach (WS) es una causa poco frecuente de anemia o hemorragia digestiva alta manifesta en pacientes de edad avanzada. Presentamos 5 apcientes, todas mujeres, edad promedio 79 años, 4 anémicas de larga evolución y 1 con melena. Tres tenían endoscopía típica de WS, 2 tenían patente difusa. Las 5 con anatomía patológica positiva: ectasias vasculares y/o microtrombos fíbrinosos y proliferación fibromuscular en la l mina propria. La biopesia esdoscópica es tan fiel como el estudio de la pieza de antrectomía. Ninguna tenía hipertensión portal, aunque la EVA sería una entidad diferente a la gastropatía vascular del cirrótico. El tratamiento conssitió en electrocoagulación monopolar de las lesiones tras fracaso del tratamiento médico en 1 caso, corticoterpia mas ferroterapia en 3, mientras que el restante no requiere tratamiento por el momento. Conclusiones: la EVA debe tenerse presente en pacientes anémicos crónicos sien diagnóstico, de edad avanzada. Las im genes endoscópicas no siempre son las típicas del estómago en sandía (WS). Se debe biopsiar el antro gastrico ante la duda. Si no responden al tratamiento con corticoides y/o hierro, el tratamiento de elección es el laser o el "heat electrocoagulación monopolar o la esclerosis. La cirurgía es el último recurso a aplicar.

Omeprazole versus placebo for acute upper gastrointestinal bleeding: randomised double blind controlled trial.

OBJECTIVE: To investigate the possible therapeutic role of omeprazole, a powerful proton pump inhibitor, in unselected patients presenting with upper gastrointestinal bleeding. DESIGN: Double blind placebo controlled parallel group study. Active treatment was omeprazole 80 mg intravenously immediately, then three doses of 40 mg intravenously at eight hourly intervals, then 40 mg orally at 12 hourly intervals. Treatment was started within 12 hours of admission and given for four days or until surgery, discharge, or death. SETTING: The medical wards of University and City Hospitals, Nottingham. SUBJECTS: 1147 consecutive patients aged 18 years or more admitted over 40 months with acute upper gastrointestinal bleeding. MAIN OUTCOME MEASURES: Mortality from all causes; rate of rebleeding, transfusion requirements, and operation rate; effect of treatment on endoscopic appearances at initial endoscopy. RESULTS: Of 1147 patients included in the intention to treat analysis, 569 received placebo and 578 omeprazole. No significant differences were found between the placebo and omeprazole groups for rates of transfusion (302 (53%) placebo v 298 (52%) omeprazole), rebleeding (100 (18%) v 85 (15%)), operation (63 (11%) v 62 (11%)), and death (30 (5.3%) v 40 (6.9%)). However, there was an unexpected but significant reduction in endoscopic signs of upper gastrointestinal bleeding in patients treated with omeprazole compared with those treated with placebo (236 (45%) placebo v 176 (33%) omeprazole; p less than 0.0001). CONCLUSIONS: Omeprazole failed to reduce mortality, rebleeding, or transfusion requirements, although the reduction in endoscopic signs of bleeding suggests that inhibition of acid may be capable of influencing intragastric bleeding. Our data do not justify the routine use of acid inhibiting drugs in the management of haematemesis and melaena.

Drug treatment for haematemesis and melaena.

Searches for useful medical treatments for upper gastrointestinal bleeding have generally ignored the need for very large case numbers if useful effects are to be detected. Available results are compatible with clinically valuable treatment effects, which can only be detected if present in very large studies.