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.

Myeloablative chemotherapy and autologous stem cell transplantation can lead to successful postengraftment mobilization of hematopoietic progenitors to support planned subsequent cycle(s) of high-dose chemotherapy and autografting in a patient with relapsed germ-cell tumor.

Salvage high-dose chemotherapy (HDC) together with autologous hematopoietic stem cell (HSC) transplantation (ASCT) represents a curative treatment option for patients with relapsed/refractory germ-cell tumor. Usually, 2-3 cycles of HDC are administered with encouraging results, and a sizeable percentage of patients experience long-term survival. However, an appreciable number of patients fail to mobilize adequate numbers of HSCs, adequate to support more than one HDC cycle. There have been no data so far on remobilization of HSCs after prior autografting. We report a unique case with relapsed germ-cell tumor that had undergone the first cycle of HDC with myeloablative doses of carboplatin-etoposide, and HSCs were mobilized successfully in the early posthematopoietic engraftment period to support further cycles of HDC. Four weeks after the first ASCT, an identical second cycle of myeloablative HDC was administered and rescued successfully with the HSCs collected after engraftment following the previous HDC cycle. The present case report illustrates that HSCs can be mobilized successfully in the early postengraftment period after myeloablative doses of carboplatin-etoposide, and these cells can be applied as the sole source of hematopoietic rescue in planned sequential cycles of myeloablative HDC, leading to successful multilineage engraftment. Provided that more extensive experience is gathered in future studies in large numbers of patients, this strategy could prove helpful in patients who cannot initially collect sufficient HSC numbers, before the first autografting cycle, and are in need of sequential HDC+ASCT cycles. A detailed literature review is provided to highlight the uniqueness of the presented case.

Case Report: Combination of Olaparib With Chemotherapy in a Patient With ATM-Deficient Colorectal Cancer.

Poly-ADP ribose polymerase (PARP) inhibitors are constantly increasing in their indications for use as anti-cancer treatment in various neoplasms, the majority of which are linked with BRCA deficiency. Preclinical data support the investigation of PARP inhibitors in other neoplasms exhibiting "BRCAness" or homologous recombination deficiency (HRD) as monotherapy as well as in combination with chemotherapy. With the current report we present the case of a heavily pretreated 55-year-old male patient diagnosed with stage IV ATM-deficient CRC, who was effectively treated with an off-label olaparib-irinotecan combination after exhaustion of all available treatment choices; furthermore, we discuss the existing data providing evidence for the use of PARP inhibitors in ATM-deficient CRC and encourage the implementation of next-generation sequencing (NGS) in patients with no other available treatment options.