Collagenous colitis and atezolizumab therapy: an atypical case.

Immune checkpoint inhibitors such as anti-CTLA-4 (cytotoxic T-lymphocyte-associated protein 4), anti-PD-1 (programmed cell death protein 1), and PD-L1 (programmed cell death protein-ligand 1) are emerging drugs that have radically changed treatment and prognosis of different types of tumors. However, despite their considerable benefits, immune checkpoint inhibitors are associated with numerous side effects involving several organs. Gastrointestinal toxicities represent some of these most common adverse events. While clinical presentation usually ranges from mild diarrhea to life-threatening colitis, typical endoscopic and histologic findings of immune-mediated colitis often resemble those of inflammatory bowel diseases. However, less common patterns are lymphocytic colitis and, rarely, collagenous colitis. Physician and pathologists must be aware of the wide spectrum of clinical and histological findings that may be encountered in immune-related gastro-intestinal toxicities. We report a rare and atypical case of collagenous colitis occurred in a woman affected by stage IV lung adenocarcinoma, on atezolizumab therapy.

Successful primary staple-repair of thoracic oesophagus after delayed presentation of a spontaneous perforation.

INTRODUCTION: Spontaneous perforation of the oesophagus is diagnosed late in over 50% of cases. Misdiagnosis may be due to atypical presentations. Primary repair is technically demanding in this setting and the risk of failure is high. PRESENTATION OF CASE: An 85 year-old lady presented with an atypical cohort of mild nonspecific symptoms in spite of a pleuro-mediastinal purulent collection secondary to an undiagnosed spontaneous perforation of the oesophagus occurred seven days before. Despite the extent of perforation (3cm in length), the late diagnosis and the necrosis of the muscular wall, the oesophagus was successfully repaired by means of a stapler. DISCUSSION: The mechanism of the atypical presentation is discussed and possible modalities of treatment of delayed oesophageal perforations are reviewed, with particular reference to primary repair and to the possible use of staplers within this setting. CONCLUSION: Even large spontaneous perforations of the oesophagus can result in a contained abscess, with no frank sepsis. Diagnosis can be missed for days in these cases. The attempt at primary repair of the oesophagus is still indicated. The use of a stapler is preferable in such cases as a perfect mucosal approximation is provided with minimal manipulation and with the use of inert, well tolerated material, which does not tend to become infected.

Correlation between induction of DNA fragmentation in lung cells from rats and humans and carcinogenic activity.

Six chemicals, known to induce lung tumors in rats, were examined for their ability to induce DNA fragmentation in primary cultures of rat and human lung cells, and in the lung of intact rats. Significant dose-dependent increases in the frequency of DNA single-strand breaks and alkali-labile sites, as measured by the single-cell gel electrophoresis (Comet) assay, were obtained in primary lung cells from male rats with the following, minimally toxic, concentrations of the six test compounds: N-nitrosodimethylamine (NDMA; 2.5-10 mM), hydrazine (HZ; 0.5-4 mM), cadmium sulfate (CD; 31.2 and 62.5 µM), 4,4'-methylene bis (2-chloroaniline) (MOCA; 31.2-125 µM), isobutyl nitrite (IBN; 7.8-31.2 µM) and tetranitromethane (TNM; 1.9-15.6 µM). Similar degrees of DNA fragmentation were obtained in primary human lung cells; however, due to inter-donor differences, the minimum effective concentrations were in some donors lower and in others higher than in rats, and IBN induced DNA damage only in one of three donors. The DNA-damaging potency of HZ was higher in rats than in humans, and the opposite was true for MOCA. In agreement with these findings, statistically significant increases in the average frequency of DNA breaks were obtained in the lung of rats given a single oral dose (1/2 LD50) of the six test compounds. These findings give evidence that genotoxic lung carcinogens may be identified by use of the DNA fragmentation/Comet assay on rat lung cells as targets cells, and show that the six compounds tested produce in primary cultures of lung cells from human donors DNA-damaging effects substantially similar to those observed in rats.