Imaging of tumour response to immunotherapy.

A wide range of cancer immunotherapy approaches has been developed including non-specific immune-stimulants such as cytokines, cancer vaccines, immune checkpoint inhibitors (ICIs), and adoptive T cell therapy. Among them, ICIs are the most commonly used and intensively studied. Since 2011, these drugs have received marketing authorisation for melanoma, lung, bladder, renal, and head and neck cancers, with remarkable and long-lasting treatment response in some patients. The novel mechanism of action of ICIs, with immune and T cell activation, leads to unusual patterns of response on imaging, with the advent of so-called pseudoprogression being more pronounced and frequently observed when compared to other anticancer therapies. Pseudoprogression, described in about 2-10% of patients treated with ICIs, corresponds to an increase of tumour burden and/or the appearance of new lesions due to infiltration by activated T cells before the disease responds to therapy. To overcome the limitation of response evaluation criteria in solid tumors (RECIST) to assess these specific changes, new imaging criteria-so-called immune-related response criteria and then immune-related RECIST (irRECIST)-were proposed. The major modification involved the inclusion of the measurements of new target lesions into disease assessments and the need for a 4-week re-assessment to confirm or not confirm progression. The RECIST working group introduced the new concept of "unconfirmed progression", into the irRECIST. This paper reviews current immunotherapeutic approaches and summarises radiologic criteria to evaluate new patterns of response to immunotherapy. Furthermore, imaging features of immunotherapy-related adverse events and available predictive biomarkers of response are presented

Conidiobolus pachyzygosporus invasive pulmonary infection in a patient with acute myeloid leukemia: case report and review of the literature.

Conidiobolus spp. (mainly C. coronatus) are the causal agents of rhino-facial conidiobolomycosis, a limited soft tissue infection, which is essentially observed in immunocompetent individuals from tropical areas. Rare cases of invasive conidiobolomycosis due to C. coronatus or other species (C.incongruus, C.lamprauges) have been reported in immunocompromised patients. We report here the first case of invasive pulmonary fungal infection due to Conidiobolus pachyzygosporus in a Swiss patient with onco-haematologic malignancy. A 71 year-old female was admitted in a Swiss hospital for induction chemotherapy of acute myeloid leukemia. A chest CT performed during the neutropenic phase identified three well-circumscribed lung lesions consistent with invasive fungal infection, along with a positive 1,3-beta-d-glucan assay in serum. A transbronchial biopsy of the lung lesions revealed large occasionally septate hyphae. A Conidiobolus spp. was detected by direct 18S rDNA in the tissue biopsy and subsequently identified at species level as C. pachyzygosporus by 28S rDNA sequencing. The infection was cured after isavuconazole therapy, recovery of the immune system and surgical resection of lung lesions. This is the first description of C. pachyzygosporus as human pathogen and second case report of invasive conidiobolomycosis from a European country

Synthesis of 3',5'-Cyclic Phosphate and Thiophosphate Esters of 2'-C-Methyl Ribonucleosides

2'-C-Methylnucleosides are known to exhibit antiviral activity against Hepatitis C virus. Since the inhibitory activity depends on their intracellular conversion to 5'-triphosphates, dosing as appropriately protected 5'-phosphates or 5'-phosphorothioates appears attractive. For this purpose, four potential pro-drugs of 2'-C-methylguanosine, i.e., 3',5'-cyclic phosphorothioate of 2'-C-methylguanosine and 2'-C,O6-dimethylguanosine, 1 and 2, respectively, the S-[(pivaloyloxy)methyl] ester of 2'-C,O6-dimethylguanosine 3',5'-cyclic phosphorothioate and the O-methyl ester of 2'-C,O6-dimethylguanosine 3',5'-cyclic phosphate, 3 and 4, respectively, have been prepared

5 ',5 '-Phosphodiesters and esterase labile triesters of 2 '-C-methylribonucleosides

Bis(2'-C-methyladenosin-5'-yl) (11), bis(2'-C-methylguanosin-5'-yl) (13), bis(2'-C-methyluridin-5'-yl) (15) and 2'-C-methylguanosin-5'-yl 2'-C-methyluridin-5'-yl (16) phosphodiesters have been prepared as pro-drug candidates for the respective 2'-C-methylribonucleoside 5'-monophosphates, expectedly exhibiting antiviral activity against Hepatitis C virus. Additionally, the bis(2'-C-methyladenosine) diester has been converted to 3-acetyloxymethoxy-2,2-bis(ethoxycarbonyl)propyl (19) or pivaloyloxymethyl (20) triester. The underlying idea is that the 5',5'-phosphodiester is first released by intracellular carboxyesterases and subsequently cleaved to nucleoside and nucleoside 5'-monophosphate by phosphodiesterases

Non-circumferential membranous resection of the trachea for paraganglioma: A case report.

Paraganglioma is a rare neuroendocrine tumor and may sometimes be located in the membranous part of the trachea. We report the case of a 52-year-old man presenting a paraganglioma just above the carina with obstructive symptoms. The patient successfully underwent a non-circumferential tracheal membranous resection, followed by latissimus dorsi muscle flap repair, under peripheral extra-corporeal membrane oxygenation (ECMO). Complex carinal resection can be avoided for tracheal membranous tumors and replaced with non-circumferential resection and direct reconstruction with a muscle flap. In addition, ECMO support may be used for airway resection and reconstruction. Tracheal membranous tumors can be managed without circumferential resection or direct anastomosis

Non-circumferential membranous resection of the trachea for paraganglioma: A case report.

Paraganglioma is a rare neuroendocrine tumor and may sometimes be located in the membranous part of the trachea. We report the case of a 52-year-old man presenting a paraganglioma just above the carina with obstructive symptoms. The patient successfully underwent a non-circumferential tracheal membranous resection, followed by latissimus dorsi muscle flap repair, under peripheral extra-corporeal membrane oxygenation (ECMO). Complex carinal resection can be avoided for tracheal membranous tumors and replaced with non-circumferential resection and direct reconstruction with a muscle flap. In addition, ECMO support may be used for airway resection and reconstruction. Tracheal membranous tumors can be managed without circumferential resection or direct anastomosis