Duodenal perforation in a SARS-CoV-2-positive patient with negative PCR results for SARS-CoV-2 in the peritoneal fluid.

OBJECTIVE: The coronavirus disease 2019 (COVID-19) pandemic has significantly affected health care organizations globally. Many aspects of this disease, as well as the risks for patients treated with multiple drug regimens to control severe COVID-19, are unclear. During emergency surgery for SARS-CoV-2-positive patients, the risk of SARS-CoV-2 exposure and transmission to the surgical staff has yet to be determined. PATIENTS AND METHODS: In this report, we describe a SARS-CoV-2-positive patient with severe respiratory syndrome treated with multiple doses of IL-6 inhibitors who presented with a perforated duodenal ulcer and underwent emergency surgery. During and after surgery, we tested for SARS-CoV-2 at the ulcer site and in the peritoneal fluid. RESULTS: The history of the patient allows for two possible interpretations of the pathogenesis of the duodenal ulcer, which could have been a stress ulcer, or a gastrointestinal ulcer associated to the use of IL-6 inhibitors. We also noticed that the ulcer site and peritoneal fluid repeatedly tested negative for SARS-CoV-2. Therefore, we reviewed the pertinent literature on gastrointestinal bleeding in patients with COVID-19 and on SARS-CoV-2 detection in the peritoneal fluid of surgical patients and discussed possible prevention strategies for bleeding and the actual risk of infection for the surgical staff. CONCLUSIONS: The first implication of this case is that the relation between repeated administration of IL-6 inhibitors and upper gastrointestinal bleeding and perforation must be investigated, and that the threshold for administering prophylactic proton pump inhibitors therapy should be carefully considered for patients with severe COVID-19. The second implication is that further testing should be performed on the peritoneal fluid of COVID-19 patients undergoing emergency surgical procedures to clarify the discordant results for the presence of SARS-CoV-2 in the peritoneal cavity and the possible risk of transmission to the surgical staff.

Development of Duodenal Ulcers due to the Discontinuation of Proton Pump Inhibitors After the Induction of Sofosbuvir Plus Ledipasvir Therapy: A Report of Two Cases.

Sofosbuvir plus ledipasvir (SOF-LDV) combination therapy is a promising therapy for post-transplant hepatitis C virus (HCV) reinfection. It is known that gastric pH elevation induces lower absorption of ledipasvir; therefore, the use of proton pump inhibitors (PPIs) should be considered regarding dose reduction after SOF-LDV therapy induction. Here, we report two patients who developed duodenal ulcers due to the discontinuation of PPIs after the induction of SOF-LDV therapy for post-transplant HCV reinfection. The first patient was a 71-year-old man who had undergone living donor liver transplantation due to HCV-related liver cirrhosis. Lansoprazole, 30 mg daily, was discontinued upon SOF-LDV therapy induction. Seven days after SOF-LDV therapy induction, gastrointestinal endoscopy revealed the presence of a duodenal ulcer. The second patient was a 54-year-old man who had undergone living donor liver transplantation due to HCV-related end-stage liver disease. Similar to the first patient, rabeprazole sodium was discontinued upon the induction of SOF-LDV therapy. Eighteen days after SOF-LDV therapy induction, gastrointestinal endoscopy revealed the presence of a duodenal ulcer. In both cases, these duodenal ulcers improved after the resumption of the administration of PPIs, and a sustained virologic response at 12 weeks was achieved by SOF-LDV therapy with PPI use. Thus, PPI use should be continued consistently during SOF-LDV therapy for post-transplant HCV reinfection.

Epstein-Barr virus association with peptic ulcer disease.

Background. Helicobacter pylori (HP) infection and nonsteroidal anti-inflammatory drugs (NSAID) use are considered the main risk to develop peptic ulcer disease (PUD). However, PUD also occurs in the absence of HP infection and/or NSAID use. Recently, we have found evidence that Epstein-Barr virus (EBV) reactivation increases the risk to develop premalignant and malignant gastric lesions. Objective. To study a possible association between EBV and PUD. Methods. Antibodies against an EBV reactivation antigen, HP, and the HP virulence factor CagA were measured in sera from 207 Mexican subjects, controls (healthy individuals, n = 129), and PUD patients (n = 78, 58 duodenal and 20 gastric ulcers). Statistical associations were estimated. Results. Duodenal PUD was significantly associated with high anti-EBV IgG titers (p = 0.022, OR = 2.5), while anti-EBV IgA was positively associated with gastric PUD (p = 0.002, OR = 10.1). Conclusions. Our study suggests that EBV reactivation in gastric and duodenal epithelium increases the risk to develop PUD.

Pancreatic anastomosis leak 15 years after simultaneous pancreas-kidney transplantation from late-onset allograft cytomegalovirus duodenal ulcers presenting with gross hematuria.

Cytomegalovirus (CMV) infection is one of the most important causes of morbidity and mortality in solid organ transplantation. It can present with hematuria, the most common urological complication in the early post-simultaneous pancreas-kidney (SPK) transplant period. In SPK transplantation, CMV infection usually occurs 1 month after transplantation. We report an instance of bladder-drained SPK transplant presenting with recurrent gross hematuria from CMV infected duodenal graft ulcers 15 years after preserved well-functioning grafts. Serum quantitative Polymerase Chain Reaction (qPCR) for CMV was negative. Postmortem duodenal graft staining for CMV was positive, and revealed the cause of the inciting ulcer. To our knowledge, our patient is the first reported case of very late onset invasive CMV disease causing duodenal graft ulcers 15 years after transplantation, as previously reported cases of posttransplant CMV disease occurred only as late as 18 months. In addition, the absence of correlation between CMV viremia and CMV-infected duodenal allograft in SPK transplant has not been reported. Our case demonstrates that CMV viral load is -unreliable to diagnose invasive CMV disease, and tissue biopsy should be obtained to avoid missed diagnosis causing high morbidity and mortality.

Successful embolization of a cytomegalovirus-related duodenal ulcer in a kidney-pancreas transplant recipient.

One of the complications that can occur in pancreas transplant is a massive intestinal hemorrhage, although such a hemorrhage is very rarely caused by ulcers due to cytomegalovirus infection. Treatment is fundamentally based on relaparatomy, although in some cases interventional radiology can be an efficient alternative because it allows the exact bleeding point to be located and therapeutic embolization to be performed. In this case, a man with diabetes type 1 who was given a simultaneous kidney-pancreas transplant had an ulcer due to cytomegalovirus infection develop in the duodenal graft (in the early postoperative period), causing a severe hemorrhage in the lower part of the gastrointestinal tract that was controlled via selective embolization of a branch of the pancreaticoduodenal artery.

[Duodenal ulcer due by cytomegalovirus as a cause of upper gastrointestinal bleeding in an immunecompetent patient]. / Ulcera duodenal por Citomegalovirus como causa de Hemoragia Digestiva Alta en un Paciente Inmunocompetente.

Duodenal ulcer due to cytomegalovirus (CMV) is quite infrequent in the inmunocompetent patient. We present an elderly patient with a history of upper urinary infections who was admitted at the hospital because of tarry black stool and coffee ground vomits. Endoscopy revealed duodenal ulcer and the histopathology confirm CMV infection. The workout was negative for human immunodeficient virus (HIV), HTLV-1 and occult cancer. The patient developed a serious infection and died due to urinary septic shock. Key words : Duodenal ulcer, cytomegalovirus, upper gastrointestinal bleeding, immunocompetent.

Upper gastrointestinal bleeding in children with haemophilia: a clinical significance of Helicobacter pylori infection.

SUMMARY: For patients with haemophilia, gastrointestinal (GI) bleeding is a life-threatening complication and can be caused by the Helicobacter pylori infection. Among children with haemophilia who had visited with GI bleeding, the prevalence of H. pylori infection and the recurrence rate after H. pylori eradication was investigated. Seven children with haemophilia A with hematemesis (age: 5.3-17.0 years) were evaluated for the causes of GI bleeding and the detection of H. pylori. Gastroendoscopy was done to find the bleeding focus and for further evaluation including rapid urease test and mucosal biopsy. Four patients had dyspepsia and abdominal pain for several weeks or months prior to hematemesis. Three patients did not show any symptoms of bleeding. From gastroendoscopy, four patients were diagnosed as duodenal ulcer, one as H. pylori associated chronic gastritis and one as haemorrhagic gastritis. One patient showing a normal finding was diagnosed with adenoid haemorrhage after nasopharyngoscopy. Helicobacter pylori infection was found in four of six patients with GI bleeding (3, duodenal ulcer; 1, H. pylori associated chronic gastritis). The patients with H. pylori infection had an eradication treatment of triple therapy and no recurrence happened. In children with haemophilia, H. pylori should also be considered as an important cause of GI bleeding. The recurrence of the infection and GI bleeding can be prevented with eradication of H. pylori. Screening test for H. pylori would be needed in children with haemophilia in endemic area.

Relationship between Helicobacter pylori virulence factors and regulatory cytokines as predictors of clinical outcome.

Helicobacter pylori infection is highly prevalent in Chile (73%). Usually a minority of infected patients develops complications such as ulcers and gastric cancer that have been associated with the presence of virulence factors (cagA, vacA) and host T helper response (Th1/Th2). Our aim was to evaluate the relationship between strain virulence and host immune response, using a multiple regression approach for the development of a model based on data collected from H. pylori infected patients in Chile. We analyzed levels of selected cytokines determined by ELISA (interleukin (IL)-12, IL-10, interferon (IFN)-gamma and IL-4) and the presence of cagA and vacA alleles polymorphisms determined by PCR in antral biopsies of 41 patients referred to endoscopy. By multiple regression analysis we established a correlation between bacterial and host factors using clinical outcome (gastritis and duodenal ulcer) as dependent variables. The selected model was described by: clinical outcome=0.867491 (cagA)+0.0131847 (IL-12/IL-10)+0.0103503 (IFN-gamma/IL-4) and it was able to explain over 90% of clinical outcomes observations (R(2)=96.4). This model considers that clinical outcomes are better explained by the interaction of host immune factors and strain virulence as a complex and interdependent mechanism.

Endoscopic diagnosis of cytomegalovirus infection of upper gastrointestinal tract in solid organ transplant recipients: Hungarian single-center experience.

BACKGROUND: Cytomegalovirus (CMV) is considered to be the major cause of upper gastrointestinal (GI) symptoms in organ transplant recipients. In the diagnosis of GI CMV infection the detection of the virus in the mucosa is essential. The aim of the study was to evaluate the significance of CMV, detected in biopsy specimens from stomach and duodenum of solid organ transplant recipients. METHODS: Data of 227 elective upper endoscopies on symptomatic organ transplant recipients were evaluated for clinical symptoms, endoscopic changes and conventional histologic alterations of mucosal biopsy samples. Qualitative PCR was performed for detection of the presence of CMV-DNA in each biopsy materials. RESULTS: CMV-DNA was detected in biopsy samples of 91 patients (40.1%) while only in 20 cases (8.8%) the signs of CMV infections were found by conventional histology (p < 0.00001). No considerable differences could be observed in symptomatic, histologic alterations between CMV-PCR positive and negative groups. There were no endoscopic changes in 25.3% of CMV-PCR positive and 5.1% of negative patients. CONCLUSIONS: Qualitative PCR is an accurate method for the detection of CMV in the mucosa of the GI tract. Further investigations are needed for determination of the exact pathological role of detected CMV.

Can duodenal ulcer perforation be linked to herpes simplex virus infection?

BACKGROUND: Both Herpes simplex infection and duodenal ulcer recur frequently, tend to remain localized, and show remissions and exacerbations. Published data on a link between the two are contradictory, and there are no data on the association of Herpes simplex infection with perforated duodenal ulcer. METHODS: 187 patients in four groups were studied: group I--controls (n = 35), group II--non-ulcer dyspepsia (n = 35), group III--chronic non-perforated duodenal ulcer (n = 35), and group IV--perforated duodenal ulcer (n = 82). Titers of IgG antibodies against HSV-1 and HSV-2 were determined using enzyme immunoassays. RESULTS: The seropositivity rate for both HSV-1 (80%) and HSV-2 (77%) was high in the control population. Among patients with perforated duodenal ulcer, antibodies against HSV-1 (94%) but not those against HSV-2 (83%), were found more frequently than in groups I and III. HSV-1 seropositivity was significantly higher in patients with a short duration of preperforation symptoms. Absolute titers for both anti-HSV-1 and anti-HSV-2 were higher in patients with perforated duodenal ulcer than in controls and those with chronic non-perforated duodenal ulcer. CONCLUSION: Herpes simplexvirus, especially HSV-1, may have a role in the causation of perforated duodenal ulcers.

Cytomegalovirus infection and development of biliary complications after liver transplantation.

BACKGROUND: Cytomegalovirus (CMV) infection is known to cause ulceration and mucosal hemorrhage in the gastrointestinal tract. Gastroduodenal and biliary complications were prospectively evaluated in 100 consecutive liver transplant patients in whom CMV was monitored during the first posttransplant year. METHOD: Gastroduodenal biopsy specimens were taken from 36 patients by endoscopies and in 28 patients by endoscopic retrograde cholangiopancreatography, and bile duct specimens were taken from three patients who underwent surgical reconstruction because of biliary complication. CMV was demonstrated from blood by the pp65 antigenemia test and from frozen sections of tissue specimens by immunohistochemistry and in situ hybridization. RESULTS: Symptomatic CMV infection, treated with ganciclovir, developed in 49 recipients: 13 (100%) of CMV seropositive donor (D+) seronegative recipient (R-) cases, 29 (45%) D+/R+ cases, and 7 (32%) D-/R+ cases. Duodenal ulcer developed in three and hemorrhagic gastritis in three recipients. CMV antigens were found from the gastroduodenal mucosa in 37 (69%) of the 54 studied recipients. The biliary complication rate was 24%. Preceding or concomitant CMV antigenemia was demonstrated in 75% of patients with a biliary complication (68% in CMV D+/R+ or D-/R+ and 100% in D+/R- recipients). The biliary complication rate was higher among recipients with CMV antigenemia, compared with recipients without (P<0.05). CMV antigenemia, CMV infection, or both in the duodenal mucosa was found in 96% of patients with a biliary complication. In two patients who underwent surgical reconstruction, CMV antigens and DNA were demonstrated in the bile ducts. CONCLUSIONS: Liver transplant patients are at risk of developing biliary complications after CMV infection, especially those with primary CMV infection.

[Atypical cytomegalovirus in renal transplantation: a new form of presentation]. / Citomegalovirus atípico en el trasplante renal: una nueva forma de presentación.

Infection due to cytomegalovirus (CMV) is the most frequent opportunistic infection following renal transplantation (RT). It is usually asymptomatic. Cytomegalovirus disease causes fever leucopenia, thrombocytopenia and slightly elevated transaminases. The development of severe invasive forms is uncommon nowadays with post-transplantation monitoring, prophylactic regimens in high-risk patients and early treatment with ganciclovir. We report two renal transplant recipients who presented with severe gastrointestinal bleeding as the first manifestation of CMV disease at 9 and 14 weeks after transplantation. In both patients repeated post-transplantation pp65 antigenemia monitoring was negative. One patient developed hypovolemic shock due to severe rectal bleeding; an atypical bleeding ulcer was detected in the ileocecal valve. The other patient presented with upper gastrointestinal hemorrhage from a bleeding duodenal ulcer. Histological and immunohistochemical study confirmed the diagnosis. Both patients were elderly and on triple therapy with tacrolimus, mycophenolate and prednisone. We discuss the role of mycophenolate and the new immunosuppressant agents as factors favoring a state of enhanced immunosuppression, which may facilitate the onset of severe atypical forms of CMV disease.