Gastrointestinal toxicities of immune checkpoint inhibitors: a multicenter retrospective analysis.

BACKGROUND: Immune checkpoint inhibitors are monoclonal antibodies that augment immune cell function and are used to treat malignancy. However, they may cause proinflammatory adverse events. This study investigated gastrointestinal (GI) adverse events associated with specific immune checkpoint inhibitors. METHODS: Charts of patients aged >18 years with a solid tumor who underwent treatment with immune checkpoint inhibitors between 1st April 2011 and 1st August 2019 were reviewed for GI toxicities. Clinical data, including interventions, treatment duration and outcomes, were recorded. RESULTS: One hundred patients were included in the study, of whom 22 experienced a GI adverse event directly attributable to immune checkpoint inhibitors. Transaminitis (9/22; 40.9%) and colitis (8/22; 36.3%) were most prevalent. The majority of events occurred within 4 cycles of treatment onset and were most prevalent with the nivolumab + ipilimumab combination (7/12; 58.3%). In 91% of cases (20/22), patients showed improvement or resolution of the event. Among the colitis cases, there was a significant difference (P=0.004) in recovery time between those who received infliximab and those who did not. Despite symptom resolution, only 7/22 were left on the same or part of the same treatment regimen. CONCLUSIONS: Most patients experienced their GI adverse events within 4 cycles of starting treatment, the most common being transaminitis and colitis. Nivolumab + ipilimumab dual therapy was most strongly associated with colitis. Most adverse events self-resolved, with infliximab being particularly helpful in improving colitis symptoms. However, most patients were unable to tolerate the same immunotherapy regimen and ultimately expired.

The gut microbiome and colorectal cancer: a review of bacterial pathogenesis.

Colorectal cancer (CRC) is the third most common newly diagnosed cancer in both men and women in the Unites States. Colonoscopy has become increasingly popular in CRC screening and represents the gold standard for detecting and removing pre-cancerous lesions. Although colonoscopy is considered a relatively safe procedure, it is invasive and bowel preparation can be challenging for patients. As interest in the gut microbiome has expanded, there have been new links established between bacteria and the development of CRC. These developing associations could prove to be a useful adjunct to colonoscopy for CRC screening in the future. This review examines current research evaluating multiple proposed pathogenic microorganisms including sulfidogenic bacteria such as Bilophila wadsworthia, as well as Streptococcus bovis, Helicobacter pylori, Bacteroides fragilis, and Clostridium septicum. This discussion primarily focuses on bacterial pathogenesis, evidence of association with CRC, and the proposed mechanisms of carcinogenesis.

Synchronous gastric and duodenal metastases from head and neck squamous cell carcinoma: a unique presentation of upper gastrointestinal bleeding.

Metastatic disease to the stomach or duodenum is an infrequent diagnosis, and head and neck squamous cell carcinoma (HNSCC) is one of the least common primary malignancies that lead to gastric or duodenal metastases. We report the case of a 65-year-old man with human immunodeficiency virus infection and previously diagnosed HNSCC who presented with melena. The patient had a percutaneous endoscopic gastrostomy tube placed 3 months prior to his presentation. Laboratory testing was significant for normocytic anemia and a digital rectal examination was positive for melena. Esophagogastroduodenoscopy revealed numerous cratered nodules with contact bleeding in the stomach as well as the duodenum that appeared malignant. Biopsies of the gastric and duodenal nodules were positive for p40 and CK 5/6, consistent with metastatic squamous cell carcinoma.

Endoscopic ultrasound in pancreatic cancer: innovative applications beyond the basics.

Endoscopic ultrasound (EUS) has become a mainstay in assisting in the diagnosis and staging of pancreatic cancer. In addition, EUS provides a modality to treat chronic pain through celiac plexus neurolysis. Currently, there is growing data and utilization of EUS in more diverse and innovative applications aimed at providing more sophisticated diagnostic, prognostic and therapeutic options for patients with pancreatic cancer. EUS delivery of chemotherapy, viral and biological vectors and fiducial markers may eventually revolutionize the way clinicians approach the care of a patient with pancreatic cancer.

Efficacy and safety of therapeutic ERCP in patients with cirrhosis: a large multicenter study.

BACKGROUND AND AIMS: Patients with cirrhosis may be less than optimal candidates for ERCP because of underlying ascites, coagulopathy, encephalopathy, and other problems. Although the risks of surgery in patients with cirrhosis are well known, few data are available regarding ERCP in patients with cirrhosis. We performed a retrospective, multicenter study of ERCP in patients with cirrhosis to evaluate outcomes, efficacy, and safety. METHODS: Multicenter retrospective study. RESULTS: A total of 538 ERCP procedures were performed on 328 patients with cirrhosis. A total of 229 patients had Child-Pugh (CP) class A, 229 patients had CP class B, and 80 patients had CP class C. Thrombocytopenia and coagulopathy were corrected before ERCP. The 30-day, procedure-related adverse events included post-ERCP pancreatitis (n = 25, 4.6%: 21 mild, 3 moderate, 1 severe), hemorrhage (n = 6, 1.1%), cholangitis (n = 15, 2.8%), perforation (n = 2, 0.4%), aspiration pneumonia (n = 5, 0.9%), bile leakage (n = 1, 0.2%), cholecystitis (n = 1, 0.2%), and death (n = 1, 0.2%). There was a higher incidence of adverse events in patients with CP class B and C disease when compared with those with CP class A disease (11.4%, 11.3%, and 6.1%, respectively; P = .048). There was no correlation between the risk of significant hemorrhage and the presence of coagulopathy or CP class, even in those who underwent a sphincterotomy. The presence of poorly controlled encephalopathy correlated with a higher overall adverse event rate (P = .003). Sub-analysis revealed that patients without primary sclerosing cholangitis had a significantly higher overall rate of adverse events, pancreatitis, bleeding, and cardiopulmonary adverse events after ERCP when compared with those with primary sclerosing cholangitis. CONCLUSIONS: Our study was performed on a large series of patients with cirrhosis undergoing ERCP. Overall, the adverse events seen in patients with cirrhosis are similar to those seen in the general population of patients undergoing ERCP, although patients with CP classes B and C have higher adverse event rates compared with those with CP class A. Patients with cirrhosis without primary sclerosing cholangitis had significantly greater adverse event rates when compared with patients with primary sclerosing cholangitis.

Retroperitoneal nodular fasciitis: a benign etiology on the differential diagnosis of malignant gastric outlet obstruction.

Nodular fasciitis is a relatively rare, benign and proliferative lesion that is not typically found in the retroperitoneal (RP) space and has not been previously reported as a cause of gastric outlet obstruction (GOO). GOOs are frequently associated with malignancies, however, benign etiologies should be considered as well. We report the first case of GOO secondary to nodular fasciitis in the form of a spontaneously regressing RP mass that was initially concerning for malignancy.

A case of periampullary adenocarcinoma in neurofibromatosis type 1.

Neurofibromatosis type 1 (NF-1) is an autosomal dominant genetic disorder with a known predisposition to gastrointestinal neoplasms such as stromal tumors and carcinoids. Adenocarcinomas (ACs) of the gastrointestinal tract are relatively rare in patients with NF-1, especially those found in the periampullary region. We present a case report of periampullary adenocarcinoma in a 56-year-old woman with NF-1 who presented with abdominal pain and obstructive jaundice.

Posterior reversible leukoencephalopathy syndrome secondary to hepatic transarterial chemoembolization with doxorubicin drug eluting beads.

Posterior reversible encephalopathy syndrome (PRES) is a rare complication of transarterial chemoembolization (TACE) used to treat liver metastases and has never been reported in a patient with metastatic uveal melanoma (UM) to the liver. We report the first case of PRES secondary to TACE with drug eluting beads (DEBs) loaded with doxorubicin in a 56-year-old woman with metastatic UM to the liver.

Extracellular matrix changes in the umbilical arteries of growth-restricted fetuses.

OBJECTIVE: This study was undertaken to determine whether the expression of extracellular matrix components (ECM) is altered in the umbilical arteries from preterm fetal growth-restricted (FGR) pregnancies. STUDY DESIGN: Preterm pregnancies with FGR were compared with appropriately grown preterm pregnancies. Umbilical artery messenger RNA (mRNA) levels for fibrillar collagens I and III, nonfibrillar collagen XIV, and decorin were determined by using relative reverse transcriptase polymerase chain reaction (RT-PCR). The mRNA expression was compared between cases and controls by using the Student t test. P < or = .05 was considered significant. RESULTS: Eight FGR cases and 5 control pregnancies were analyzed. Mean counts per minute (cpm) +/- SEM for collagen I and collagen III were increased in FGR pregnancies. There were no differences in mRNA expression of collagen XIV or decorin. CONCLUSION: Increased mRNA expression of collagen I and III, but not collagen XIV or decorin, is found in the umbilical arteries of preterm FGR pregnancies.