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Background: We performed a pooled analysis of TRIBE and TRIBE2 studies to assess the efficacy and safety of the intensification of upfront chemotherapy backbone - from doublets to the triplet FOLFOXIRI - in combination with bevacizumab (bev) in patients with early-onset metastatic colorectal cancer (EO-mCRC; aged <50 years) and to explore whether EO-mCRCs have a peculiar tumour genomic profiling., Materials and Methods: Subgroup analyses according to age (<50 versus ≥50 years) and treatment (FOLFOXIRI/bev versus doublets/bev) were carried out for rates of any grade and grade ≥3 (≥G3) overall and singular adverse events, progression-free survival (PFS), overall survival (OS) and objective response rate (ORR). Tumour genomic profiling was obtained using a DNA-based next-generation sequencing platform., Results: Of 1187 patients included, 194 (16%) patients were aged <50 years. Females were more frequently diagnosed with EO-mCRC (P = 0.04). Patients aged <50 years showed a lower risk of ≥G3 neutropenia (P = 0.07), diarrhoea (P = 0.04), asthenia (P = 0.008) and a higher risk of any grade nausea (P < 0.01) and vomiting (P < 0.01). Patients receiving FOLFOXIRI/bev more frequently experienced ≥G3 chemotherapy-related adverse events respect to doublets/bev, regardless of age (P interaction  = 0.60). FOLFOXIRI/bev was associated to a lower incidence of neutropenia (P = 0.04) and asthenia (P = 0.01) in patients <50 years old, than those aged ≥50 years. PFS, OS and ORR did not differ according to age (PFS P = 0.81, OS P = 0.44, ORR P = 0.50) and no interaction between age and the benefit from the intensification of upfront chemotherapy was observed (PFS P interaction  = 0.72, OS P interaction  = 0.54, ORR P interaction  = 0.65). Genomic profiling was assessed in 296 patients, showing an enrichment of FBXW7 and POLE mutations in EO-mCRC., Conclusions: Upfront FOLFOXIRI/bev shows a favourable efficacy/safety balance in EO-mCRC., Trial Registration: Clinicaltrials.gov Identifiers NCT00719797, NCT0233-9116., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: Gliosarcoma (GS) refers to the presence of mesenchymal differentiation (as seen using light microscopy) in the setting of glioblastoma (GB, an astrocytoma, WHO Grade 4). Although the same approach to treatment is typically adopted for GS and GB, there remains some debate as to whether GS should be considered a discrete pathological entity. Differences between these tumors have not been clearly established at the molecular level., Methods: Patients with GS (n=48) or GB (n=1229) underwent molecular profiling (MP) with a pan-cancer panel of tests as part of their clinical care. The methods employed included next-generation sequencing (NGS) of DNA and RNA, copy number variation (CNV) of DNA and immunohistochemistry (IHC). The MP comprised 1153 tests in total, although results for each test were not available for every tumor profiled. We analyzed this data retrospectively in order to determine if our results were in keeping with what is known about the pathogenesis of GS by contrast with GB. We also sought novel associations between the MP and GS vs. GB which might improve our understanding of pathogenesis of GS., Results: Potentially meaningful associations (p<0.1, Fisher's exact test (FET)) were found for 14 of these tests in GS vs. GB. A novel finding was higher levels of proteins mediating immuno-evasion (PD-1, PD-L1) in GS. All of the differences we observed have been associated with epithelial-to-mesenchymal transition (EMT) in other tumor types. Many of the changes we saw in GS are novel in the setting of glial tumors, including copy number amplification in LYL1 and mutations in PTPN11., Conclusions: GS shows certain characteristics of EMT, by contrast with GB. Treatments targeting immuno-evasion may be of greater therapeutic value in GS relative to GB.

Background: Because of the increasing number of long-term survivors of metastatic testicular germ-cell cancer, a general concern has been secondary morbidities, especially cardiovascular risk factors., Patients and Methods: Thirty-two patients treated with cisplatin- and doxorubicin-containing chemotherapy > or = 13 years before the time of analyses were evaluated for neuro-, oto-, pulmonary-, vascular- and gonadal toxicity including evaluation of myocardial damage and cardiovascular risk factors and analysis of microcirculation., Results: Thirty percent of the patients showed abnormal left ventricle function. Elevated follicle stimulating hormone (FSH) and luteinising hormone (LH) levels in 75% of patients were often associated with low testosterone levels. Elevated total cholesterol levels were found in 82% and higher triglyceride levels in 44% of patients, most of them were overweight. About 25% of the patients developed diastolic arterial hypertension after chemotherapy. Reduced hearing was confirmed in 23% of patients, especially at frequencies higher than 3000 Hz. Moreover, 53% of patients presented transient evoked otoacoustic emissions. In 38% of patients non-symptomatic neuropathy was detected, in 28% symptomatic neuropathy, and in 6% disabling polyneuropathy. In 80% of patients with neuropathic symptoms additional morphological and functional abnormalities were found by nailfold capillary videomicroscopy, compared to only 57% of the patients without neuropathic symptoms., Conclusions: Patients cured by cisplatin-based chemotherapy for metastatic testicular cancer have to be cognizant of their unfavorable cardiovascular risk profile, that might be a greater risk than developing a relapse or second malignancy.

Fourteen patients with 5-fluorouracil (5-FU) refractory, progressive colorectal cancer metastatic to liver and/or lung were treated with continuous oral trofosfamide, an alkylating agent structurally related to cyclophosphamide and ifosfamide. Trofosfamide was given daily at 200 mg/day. No objective partial or complete responses were seen in 14 evaluable patients. There were four patients with stable disease or minor responses; the median duration of stable disease during trofosfamide treatment was 14 weeks, with of range of 12-36 weeks. Mild to moderate side effects were reported in seven patients including grade 1-2 nausea in four patients, grade 1 leukopenia in two patients and grade 1 anemia in one patient. Trofosfamide in this dose and schedule shows minor activity in 5-FU refractory colorectal cancer. Because of very little side effects, dose escalations appear to be possible.

This article describes a study that evaluates a combined arthroscopy and high tibial osteotomy treatment protocol incorporating: a new curved and double-bladed barrel vault (dome) osteotomy guide; measurement of the mechanical axis of the limb during surgery as well as measurement of the femorotibial angle and mechanical axis before and after surgery; and prior arthroscopic evaluation and debridement. Forty-five high tibial osteotomies were performed in 42 patients. All 45 knees had varus angular deformity. Arthroscopy confirmed osteoarthritis in all 45 knees and grade 4 medial compartment chondromalacia in 44 of 45 knees. Patients were evaluated preoperatively and postoperatively using a grading scale modified from that of the Hospital for Special Surgery. Follow-up of patients ranged from 1 to 6 years (mean: 3.1 years). The average clinical score was 57.4 preoperatively and 89.8 postoperatively, an improvement of 56.4%. All patients achieved and maintained pain relief compared with their preoperative status. No patient needed total knee replacement. These results indicate that in patients with unicompartmental osteoarthritis with angular deformity, high tibial barrel vault (dome) osteotomy can improve the quality of life while preserving the knee joint. There was no relationship between clinical score and either patient age or severity of lateral compartment chondromalacia. Therefore, osteotomy may be appropriate for a larger population than generally thought.

Arthrography and arthroscopy were compared on a prospective basis in 100 consecutive and unselected knees, all in patients who underwent arthrography, arthroscopy, and surgery. Arthroscopy was found to be more accurate than arthrography in the diagnosis of medial and lateral meniscus and anterior cruciate ligament lesions. Because of its easy availability and relatively low cost, arthrography continues to be a useful extension of the physical examination of the knee, serving as a further diagnostic screening technique. However, arthroscopy is recommended in all patients prior to surgery because it provides more complete and more accurate delineation of intra-articular lesions.

Two patients with an ossicle of the meniscus are described. Radiologic differentiation from osteochondral loose body or chondrocalcinosis can be made by its ossified appearance and its location within the meniscus. Correct diagnosis is important so that unnecessary surgery is avoided and a protracted search for a free fragment is not carried out.

To assess the continued value of arthrograms in the wake of arthroscopic diagnosis, an analysis of arthrographic data on 240 knees was carried out. The accuracy, sensitivity, and specificity of the arthograms were compared with the arthroscopic findings for each knee. For meniscal lesions, the arthrogram is reasonably accurate. An algorithm is presented that defines the relative roles of arthrography and arthroscopy.