Characteristics of appendicitis after immune checkpoint inhibitor therapy among cancer patients.

PURPOSE: Immune checkpoint inhibitor (ICI) therapy has revolutionized cancer care but is associated with immune-related adverse events (irAEs). Recent case reports raised the concern that acute appendicitis may be an irAE. In this study, we sought to describe the disease course of post-ICI therapy appendicitis and its associated complications. METHODS: Adult patients who had an International Classification of Diseases code for appendicitis within the first 2 years after initiating ICI therapy from January 2010 to April 2021 and who had imaging evidence of appendicitis were studied retrospectively. RESULTS: 13,991 patients were identified who had ICI exposure during the study period, 44 had codes for appendicitis, 10 of whom met the inclusion criteria. Their median age at the time of diagnosis was 59 years. The median time from ICI therapy initiation to appendicitis onset was 188 days. The most common presenting symptoms were abdominal pain (70%) and fever (40%). Abscesses were present in two patients, and a perforation was present in one. All 10 patients received broad-spectrum antibiotics. Five patients needed surgery or interventional radiology drainage. Nine patients had resolution of appendicitis symptoms after treatment. CONCLUSION: Post-ICI therapy appendicitis is rare but presents similarly to and has similar complications rates as conventional appendicitis. Appendectomy remains the mainstay of treatment, but its use can be limited in cancer patients. The decision to continue ICI therapy remains at the discretion of the clinician. Further studies are needed to bring awareness to and advance the understanding of this clinical entity.

Perforated appendicitis induced by pembrolizumab: a case report and review of the literature.

Monoclonal antibodies against programmed cell death protein 1 (PD-1) and PD-1 ligand 1 (PD-L1) are the main representatives in the field of immunotherapy and their indications are constantly increasing in medical oncology and hematology during the last decade. They are associated with long-lasting responses and an acceptable toxicity profile, although they may infrequently cause life-threatening complications requiring prolonged hospitalization or urgent interventions. With the current report, we present the case of a 75-year-old woman diagnosed with stage IV lung adenocarcinoma, who developed acute abdominal pain without preceding symptomatology while on pembrolizumab-pemetrexed maintenance treatment. A contained rupture of the appendix was found, for which she was managed conservatively. Subsequent endoscopic as well as histopathological findings from biopsies obtained via colonoscopy associated the clinical and imaging findings with grade 4 immune-mediated colitis. Interestingly, high-grade colitis is more frequent with anti-CTLA-4 agents in comparison to anti-PD-1 agents; moreover, most cases of anti-PD-1-mediated colitis present with preceding symptomatology (like diarrhea or vomiting), while cases or colonic perforation are extremely rare if ever described.

Near Real-Time Surveillance to Assess the Safety of the 9-Valent Human Papillomavirus Vaccine.

BACKGROUND AND OBJECTIVES: Human papillomavirus is the most common sexually transmitted infection in the United States and causes certain anogenital and oropharyngeal cancers. The 9-valent human papillomavirus vaccine (9vHPV) provides protection against additional types not included in the quadrivalent vaccine. We conducted near real-time vaccine safety surveillance for 24 months after the vaccine became available in the Vaccine Safety Datalink. METHODS: Immunizations and adverse events were extracted weekly from October 2015 to October 2017 from standardized data files for persons 9 to 26 years old at 6 Vaccine Safety Datalink sites. Prespecified adverse events included anaphylaxis, allergic reaction, appendicitis, Guillain-Barré syndrome, chronic inflammatory demyelinating polyneuropathy, injection site reaction, pancreatitis, seizure, stroke, syncope, and venous thromboembolism. The observed and expected numbers of events after 9vHPV were compared weekly by using sequential methods. Both historical and concurrent comparison groups were used to identify statistical signals for adverse events. Unexpected signals were investigated by medical record review and/or additional analyses. RESULTS: During 105 weeks of surveillance, 838 991 doses of 9vHPV were administered. We identified unexpected statistical signals for 4 adverse events: appendicitis among boys 9 to 17 years old after dose 3; pancreatitis among men 18 to 26 years old; and allergic reactions among girls 9 to 17 years old and women 18 to 26 years old after dose 2. On further evaluation, which included medical record review, temporal scan analysis, and additional epidemiological analyses, we did not confirm signals for any adverse events. CONCLUSIONS: After 2 years of near real-time surveillance of 9vHPV and several prespecified adverse events, no new safety concerns were identified.

Acute appendicitis presenting as pneumoperitoneum in a teenage boy undergoing chemotherapy.

Chemotherapy of paediatric haematological malignancies can induce infectious complications of the gastrointestinal tract, with predilection of the ileocaecal region. Common causes of right lower abdominal pain in the febrile patient with neutropaenia include acute appendicitis, typhlitis, ileus and intussusception. In this case report, we describe a teenage boy with acute appendicitis presenting with pneumoperitoneum during his course of chemotherapy. The incidence, aetiology, diagnosis, investigations and management of this uncommon presentation in a common disease are discussed. The controversial topic of the management of acute appendicitis in a febrile patient with neutropaenia is also reviewed and discussed.

Periappendicitis during adalimumab treatment for ileocecal Crohn's disease in a 29-year-old male.

A 29-year-old male was diagnosed with ileocolic Crohn's disease (CD) approximately 2 years ago. Adalimumab was prescribed as CD remission induction therapy. Three months after beginning adalimumab, watery diarrhea and lower abdominal pain developed. He was admitted under a diagnosis of CD exacerbation. Despite fasting and antibiotic treatment, symptoms of acute panperitonitis appeared. He was diagnosed as acute appendicitis and we performed emergency surgery for peritoneal drainage and ileocecal resection on the fifth hospital day. We diagnosed periappendicitis based on the operative findings. This is the first report of periappendicitis with CD during adalimumab treatment.

Perforated appendicitis after intravenous immunoglobulin therapy in a term neonate with haemolytic jaundice.

Neonatal appendicitis is a rare clinical condition that may cause high morbidity and mortality if diagnosis is delayed. There is usually an underlying disease; it can also be a localized form of necrotizing enterocolitis. Here, we present a term neonate who was treated with intravenous immunoglobulin because of severe isoimmune hemolytic jaundice. The patient developed abdominal symptoms within 10 hours of therapy, was diagnosed with acute perforated appendicitis and completely recovered after surgery.

Meralgia Paresthetica as a Presentation of Acute Appendicitis in a Girl With Acute Lymphoblastic Leukemia.

A 7-year-old girl with Philadelphia chromosome-positive acute lymphoblastic leukemia developed recurrent fever and meralgia paresthetica (MP) during chemotherapy, which resolved after administration of antibiotics. Five months after the onset of these symptoms, enhanced computed tomography showed a periappendiceal abscess extending into the psoas muscle. The cause of her fever and MP was thought to be appendicitis, which probably developed during induction chemotherapy but did not result in typical abdominal pain. Patients with recurrent fever and MP should be evaluated by imaging examinations including computed tomography to search for appendicitis.

Barium-induced appendicitis mimicking accidental ingestion of a dental metal crown in radiological findings.

Barium appendicitis is a rare complication that has only been reported in a small number of case reports in the medical literature. A 57-year-old male presented to the emergency room with a sudden onset of sharp right lower quadrant abdominal pain. He had undergone contrast barium examination of his stomach 2 months previously as part of a periodic examination for gastric cancer. The radiological findings showed that the shape and radiopaque levels were similar to those of a dental metal crown silhouette. The patient was strongly suspected to have a localized intra-abdominal abscess due to ileocaecal perforation with a foreign body such as a dental metal crown. Emergency surgery revealed acute phlegmonous appendicitis. The resected specimen demonstrated a phlegmonous appendix which contained solid coproma. Pathological diagnosis and composition analysis confirmed the onset of appendicitis to be a result of the patient's ingestion of barium sulfate.

Barium appendicitis 1 month after a barium meal.

Because barium sulfate (BaSO(4)) is not harmful to the mucosa, it is widely used for gastrointestinal imaging. Barium appendicitis is a very rare complication of barium meals and barium enema. We report a case of acute appendicitis associated with retained appendiceal barium. A 47-year-old man presented with right lower abdominal pain after upper gastrointestinal imaging was performed using barium 1 month earlier. The abdominal plain roentgenogram showed an area of retained barium in the right lower quadrant. Multiplanar reconstruction of computed tomography scans showed barium retention in the appendix. Emergency appendectomy was performed. A cross section of the specimen revealed the barium mass. Barium-associated appendicitis is a very rare clinical entity but we should be cautious of this uncommon disease when we encounter barium deposits in the appendix after barium examination. This report is significant because barium was identified both macroscopically and microscopically.

Decreased incidence of febrile episodes with antibiotic prophylaxis in the treatment of decitabine for myelodysplastic syndrome.

We analyzed the role of antibiotic prophylaxis during decitabine treatment for MDS. The primary endpoint was the incidence of febrile episodes. The total number of decitabine cycles given to 28 patients was 131, and febrile episodes occurred in 15 cycles (11.5%). Antibiotic prophylaxis was orally administered in 95 cycles (72.5%). Febrile episodes were significantly less frequent among patients who received antibiotic prophylaxis (7.4%) than in those without prophylaxis (22.2%) (P=0.017). In conclusion, antibiotic prophylaxis reduced the incidence of febrile episodes in patients who received decitabine treatment for MDS, especially at earlier cycles and in the presence of severe cytopenia.

No association between non-steroidal anti-inflammatory drugs and acute appendicitis in a case-control study.

BACKGROUND: A recent case-control study reported an association between non-steroidal anti-inflammatory drug (NSAID) use and acute appendicitis. This association was investigated in a case-control study of patients, aged 30 years and over, admitted as an emergency to hospitals in Tayside between 1989 and 1992, who had appendicectomy for acute appendicitis. METHODS: A record-linkage database containing records of dispensed prescriptions and hospital admissions was used. A total of 223 patients were identified. The medical records of 161 were checked, of which 138 were valid cases, and information on white cell count and NSAID exposure was recorded. Community and hospital controls were generated. RESULTS: Some 9.0 per cent of patients were prescribed NSAIDs within 90 days of hospitalization, compared with 7.6 per cent of community controls and 11.5 per cent of hospital controls. The odds ratio was 1.21 (95 per cent confidence interval 0.73-2.01) and 0.75 (0.43-1.32) respectively. There was no significant difference in white cell count between exposed and non-exposed cases. No increased risk of appendicectomy was associated with aspirin use: odds ratio 1.67 (0.52-5.30) and 0.37 (0.12-1.13) using community and hospital controls respectively. CONCLUSION: Appendicectomy for acute appendicitis is not associated with increased prior use of NSAIDs.

Non-steroidal anti-inflammatory drugs and appendicitis in patients aged over 50 years.

In a retrospective study 84 patients aged > or = 50 years undergoing emergency appendicectomy were matched for age and sex with 84 randomly selected emergency admissions as controls. Of the former, 31 (37 per cent) were taking non-steroidal anti-inflammatory drugs. (NSAIDs) at admission, compared with nine (11 per cent) of the controls (P < 0.01). In the study group a suppression of the white cell count was identified on admission in those taking NSAIDs (mean 11.9 x 10(9) l-1) compared with those not (mean 14.8 x 10(9) l-1) (P = 0.007). This is the first reported association between appendicitis and NSAIDs. The relative risk by odds ratio was substantially increased at 6.5 (95 per cent confidence interval 2.1-8.8). An NSAID-related impairment of host defences leading to failure in the resolution of inflammatory episodes may explain this association. It is further postulated that the suppression of the white cell response may be a marker of such an effect.