Gut Microbiome Composition and Its Metabolites Are a Key Regulating Factor for Malignant Transformation, Metastasis and Antitumor Immunity.

The genetic and metabolomic abundance of the microbiome exemplifies that the microbiome comprises a more extensive set of genes than the entire human genome, which justifies the numerous metabolic and immunological interactions between the gut microbiota, macroorganisms and immune processes. These interactions have local and systemic impacts that can influence the pathological process of carcinogenesis. The latter can be promoted, enhanced or inhibited by the interactions between the microbiota and the host. This review aimed to present evidence that interactions between the host and the gut microbiota might be a significant exogenic factor for cancer predisposition. It is beyond doubt that the cross-talk between microbiota and the host cells in terms of epigenetic modifications can regulate gene expression patterns and influence cell fate in both beneficial and adverse directions for the host's health. Furthermore, bacterial metabolites could shift pro- and anti-tumor processes in one direction or another. However, the exact mechanisms behind these interactions are elusive and require large-scale omics studies to better understand and possibly discover new therapeutic approaches for cancer.

Antibiotic-Related Changes in Microbiome: The Hidden Villain behind Colorectal Carcinoma Immunotherapy Failure.

The interplay between drugs and microbiota is critical for successful treatment. An accumulating amount of evidence has identified the significant impact of intestinal microbiota composition on cancer treatment response, particularly immunotherapy. The possible molecular pathways of the interaction between immune checkpoint inhibitors (ICIs) and the microbiome can be used to reverse immunotherapy tolerance in cancer by using various kinds of interventions on the intestinal bacteria. This paper aimed to review the data available on how the antibiotic-related changes in human microbiota during colorectal cancer (CRC) treatment can affect and determine ICI treatment outcomes. We also covered the data that support the potential intimate mechanisms of both local and systemic immune responses induced by changes in the intestinal microbiota. However, further better-powered studies are needed to thoroughly assess the clinical significance of antibiotic-induced alteration of the gut microbiota and its impact on CRC treatment by direct observations of patients receiving antibiotic treatment.

New strategies in the diagnosis and treatment of immune-checkpoint inhibitor-mediated colitis.

Immune-checkpoint inhibitor-mediated colitis (IMC) is an increasingly recognized adverse event in cancer immunotherapy, particularly associated with immune checkpoint inhibitors (ICIs) such as anti-cytotoxic T-lymphocyte antigen-4 and anti-programmed cell death protein-1 antibodies. As this revolutionary immunotherapy gains prominence in cancer treatment, understanding, diagnosing, and effectively managing IMC becomes paramount. IMC represents a unique challenge due to its immune-mediated nature and potential for severe complications. However, a precise picture of IMC pathophysiology is currently unavailable. Therefore, we aimed to summarize the existing data while acknowledging the need for further research. This comprehensive review explores the mechanisms underlying ICIs, gastrointestinal adverse effects, and, in particular, IMC's incidence, prevalence, and features. Our review also emphasizes the importance of recognizing IMC's distinct clinical and histopathological features to differentiate it from other forms of colitis. Furthermore, this paper highlights the urgent need for evolving diagnostic methods, therapeutic strategies, and a multidisciplinary approach to effectively manage IMC.

Effectiveness and safety of COVID-19 vaccines in patients with oncological diseases: State-of-the-art.

Although the coronavirus disease 2019 (COVID-19) pandemic was declared to be no longer "a public health emergency of international concern" with its wide range of clinical manifestations and late complications, severe acute respiratory syndrome coronavirus 2 infection proved to be a serious threat, especially to the elderly and patients with comorbidities. Patients with oncologic diseases are vulnerable to severe infection and death. Indeed, patients with oncohematological diseases have a higher risk of severe COVID-19 and impaired post-vaccination immunity. Unfortunately, cancer patients are usually excluded from vaccine trials and investigations of post-vaccinal immune responses and the effectiveness of the vaccines. We aimed to elucidate to what extent patients with cancer are at increased risk of developing severe COVID-19 and what is their overall case fatality rate. We also present the current concept and evidence on the effectiveness and safety of COVID-19 vaccines, including boosters, in oncology patients. In conclusion, despite the considerably higher mortality in the cancer patient group than the general population, countries with high vaccination rates have demonstrated trends toward improved survival of cancer patients early and late in the pandemic.

Factors affecting complications development and mortality after single lung transplant.

Lung transplantation (LT) is a life-saving therapeutic procedure that prolongs survival in patients with end-stage lung disease. Furthermore, as a therapeutic option for high-risk candidates, single LT (SLT) can be feasible because the immediate morbidity and mortality after transplantation are lower compared to sequential single (double) LT (SSLTx). Still, the long-term overall survival is, in general, better for SSLTx. Despite the great success over the years, the early post-SLT period remains a perilous time for these patients. Patients who undergo SLT are predisposed to evolving early or late postoperative complications. This review emphasizes factors leading to post-SLT complications in the early and late periods including primary graft dysfunction and chronic lung allograft dysfunction, native lung complications, anastomosis complications, infections, cardiovascular, gastrointestinal, renal, and metabolite complications, and their association with morbidity and mortality in these patients. Furthermore, we discuss the incidence of malignancy after SLT and their correlation with immunosuppression therapy.

Host response to immune checkpoint inhibitors contributes to tumor aggressiveness.

BACKGROUND: Immune checkpoint inhibitors (ICIs) have made a paradigm shift in clinical oncology due to unprecedented long-term remissions. However, only a small proportion of patients respond to ICI therapy. It is, therefore, essential to understand the mechanisms driving therapy resistance and to develop strategies for increasing response rates. We previously demonstrated that in response to various cancer treatment modalities, the host activates a range of biological processes that promote tumor regrowth and metastasis. Here, we characterize the host-mediated response to ICI therapy, and investigate its contribution to therapy resistance. METHODS: Tumor cell migration, invasion and motility were assessed in the presence of plasma from ICI-treated mice and patients. Immune cell composition in peripheral blood and tumors of ICI-treated mice was assessed by flow and mass cytometry. Plasma host factors driving tumor aggressiveness were identified by proteomic profiling, followed by bioinformatic analysis. The therapeutic effect of inhibiting host-mediated processes in ICI-treated mice was assessed in a tumor model. RESULTS: Tumor cells exhibit enhanced migratory and invasive properties in vitro on exposure to plasma from anti-PD1-treated mice. Moreover, mice intravenously injected with plasma-exposed tumor cells display increased metastatic burden and mortality rate in comparison to control arms. Furthermore, tumors from anti-PD1-treated mice as well as Matrigel plugs containing plasma from anti-PD1-treated mice are highly infiltrated with immune cell types associated with both antitumor and protumor activity. These collective findings suggest that anti-PD1 treatment induces a systemic host response that potentially counteracts the drug's therapeutic activity. Proteomic profiling of plasma from anti-PD1-treated mice reveals an activation of multiple biological pathways associated with tumor aggressiveness. Consequently, blocking IL-6, one of the key drivers of the identified biological pathways, counteracts ICI-induced metastatic properties in vitro and improves ICI treatment efficacy in vivo. Lastly, plasma samples from ICI-treated non-small cell lung cancer patients differentially affect tumor cell aggressiveness in vitro, with enhanced tumor cell motility correlating with a worse clinical outcome. CONCLUSIONS: ICI therapy induces host-mediated processes that contribute to therapy resistance. Identification and analysis of such processes may lead to the discovery of biomarkers for clinical response and strategies for overcoming therapy resistance.

What could microRNA expression tell us more about colorectal serrated pathway carcinogenesis?

In the last two decades, the vision of a unique carcinogenesis model for colorectal carcinoma (CRC) has completely changed. In addition to the adenoma to carcinoma transition, colorectal carcinogenesis can also occur via the serrated pathway. Small non-coding RNA, known as microRNAs (miRNAs), were also shown to be involved in progression towards malignancy. Furthermore, increased expression of certain miRNAs in premalignant sessile serrated lesions (SSLs) was found, emphasizing their role in the serrated pathway progression towards colon cancer. Since miRNAs function as post-transcriptional gene regulators, they have enormous potential to be used as useful biomarkers for CRC and screening in patients with SSLs particularly. In this review, we have summarized the most relevant information about the specific role of miRNAs and their relevant signaling pathways among different serrated lesions and polyps as well as in serrated adenocarcinoma. Additional focus is put on the correlation between gut immunity and miRNA expression in the serrated pathway, which remains unstudied.

Uteroplacental apoplexy associated with invasive cervical neoplasm.

The cervical cancer is the worldwide second neoplasia in women, after the breast cancer. The incidence of invasive carcinoma in pregnancy is 1÷2000 to 1÷10 000 pregnancies. In most of the studies, almost all the patients had microinvasive carcinoma or limited cervical carcinoma at the cervix level. In the uteroplacental apoplexy, pathologically, retroplacental hematoma is formed while the fetus is still in the uterus. When speaking about the uteroplacental apoplexy, the fetal mortality is 100% and the maternal mortality can reach 5%. The particularity of the presented case is the association of the invasive cervical neoplasm, pathology unknown to the patient, with uteroplacental apoplexy, diagnosis for which she was hospitalized as an emergency. After the extraction of the dead fetus by segmental-transversal cesarean section, we continued to perform the total hysterectomy with adnexectomy. The fetus, the placenta, the uterus and the ovaries were sent for histopathological examination. Subsequently, the histopathological bulletin revealed cervical lesions in the neck of type cervical intraepithelial neoplasia (CIN) I, CIN II, CIN III, metaplastic squamous epithelium and moderately differentiated squamous cell carcinoma.

Cervical adenocarcinoma generator of procoagulant status and ischemic stroke.

The procoagulant status of neoplastic patients is well known in medical literature, but in the last years there is attempted a correlation between the histological types of neoplasia and the risk for thrombotic strokes. We present the case of a 44-years-old patient undergoing early menopause, who was diagnosed with cervical tumor of the serous adenocarcinoma type. The patient underwent external radiotherapy, and, in the seventh day of treatment, she suffered a frontal-temporal-parietal ischemic stroke with left hemiplegia. The blood testing highlighted procoagulant products (double fibrinogen compared to normal values, deficit of antithrombin and a high number of thrombocytes). The patient received neurological and rehabilitation treatment, at first with Heparin, followed by the administration of an antiaggregant. During this treatment, the deficit remained unchanged. She continued the neurological and rehabilitation treatment, followed by radiotherapy, with a good evolution. Six months after the stroke, it was decided the surgical tumor ablation of cytoreduction. The post-surgery histological examination highlighted specific changes due to post-surgery radiotherapy, without the presence of any neoplastic cells. The imagistic evaluation, computed tomography (CT) every three months after surgery, did not highlight any suggestive dissemination elements. The occurrence of an ischemic stroke in a patient with endocervical neoplasm of the adenocarcinoma type during radiotherapy imposed the discharge of chemotherapy, with subsequent imaging, biological and histopathological monitoring after surgery. The cause of stroke in this case is determined by the hypercoagulant status in the context of the developed neoplasia, the patient being free of any other risk factors.