Immunotherapy for colorectal cancer: where are we heading?

Introduction: In the last few years, significant advances in molecular biology have provided new therapeutic options for colorectal cancer (CRC). The development of new drugs that target the immune response to cancer cells seems very promising and has already been established for other tumor types. In particular, the use of immune checkpoint inhibitors seems to be an encouraging immunotherapeutic strategy. Areas covered: In this review, the authors provide an update of the current evidence related to this topic, though most immunotherapies are still in early-phase clinical trials for CRC. To understand the key role of immunotherapy in CRC, the authors discuss the delicate balance between immune-stimulating and immune-suppressive networks that occur in the tumor microenvironment. Expert opinion: Modulation of the immune system through checkpoint inhibition is an emerging approach in CRC therapy. Nevertheless, selection criteria that could enable the identification of patients who may benefit from these agents are necessary. Furthermore, potential prognostic and predictive immune biomarkers based on immune and molecular classifications have been proposed. As expected, additional studies are required to develop biomarkers, effective therapeutic strategies and novel combinations to overcome immune escape resistance and enhance effector response

Energy Resolution Performance of the CMS Electromagnetic Calorimeter

The energy resolution performance of the CMS lead tungstate crystal electromagnetic calorimeter is presented. Measurements were made with an electron beam using a fully equipped supermodule of the calorimeter barrel. Results are given both for electrons incident on the centre of crystals and for electrons distributed uniformly over the calorimeter surface. The electron energy is reconstructed in matrices of 3 times 3 or 5 times 5 crystals centred on the crystal containing the maximum energy. Corrections for variations in the shower containment are applied in the case of uniform incidence. The resolution measured is consistent with the design goals

Mortality and pulmonary complications in patients undergoing surgery with perioperative SARS-CoV-2 infection: an international cohort study

Background: The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on postoperative recovery needs to be understood to inform clinical decision making during and after the COVID-19 pandemic. This study reports 30-day mortality and pulmonary complication rates in patients with perioperative SARS-CoV-2 infection. Methods: This international, multicentre, cohort study at 235 hospitals in 24 countries included all patients undergoing surgery who had SARS-CoV-2 infection confirmed within 7 days before or 30 days after surgery. The primary outcome measure was 30-day postoperative mortality and was assessed in all enrolled patients. The main secondary outcome measure was pulmonary complications, defined as pneumonia, acute respiratory distress syndrome, or unexpected postoperative ventilation. Findings: This analysis includes 1128 patients who had surgery between Jan 1 and March 31, 2020, of whom 835 (74·0%) had emergency surgery and 280 (24·8%) had elective surgery. SARS-CoV-2 infection was confirmed preoperatively in 294 (26·1%) patients. 30-day mortality was 23·8% (268 of 1128). Pulmonary complications occurred in 577 (51·2%) of 1128 patients; 30-day mortality in these patients was 38·0% (219 of 577), accounting for 81·7% (219 of 268) of all deaths. In adjusted analyses, 30-day mortality was associated with male sex (odds ratio 1·75 [95% CI 1·28–2·40], p\textless0·0001), age 70 years or older versus younger than 70 years (2·30 [1·65–3·22], p\textless0·0001), American Society of Anesthesiologists grades 3–5 versus grades 1–2 (2·35 [1·57–3·53], p\textless0·0001), malignant versus benign or obstetric diagnosis (1·55 [1·01–2·39], p=0·046), emergency versus elective surgery (1·67 [1·06–2·63], p=0·026), and major versus minor surgery (1·52 [1·01–2·31], p=0·047). Interpretation: Postoperative pulmonary complications occur in half of patients with perioperative SARS-CoV-2 infection and are associated with high mortality. Thresholds for surgery during the COVID-19 pandemic should be higher than during normal practice, particularly in men aged 70 years and older. Consideration should be given for postponing non-urgent procedures and promoting non-operative treatment to delay or avoid the need for surgery. Funding: National Institute for Health Research (NIHR), Association of Coloproctology of Great Britain and Ireland, Bowel and Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, NIHR Academy, Sarcoma UK, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research

Fingerprint Change: Not Visible, But Tangible

Handâfoot syndrome, a chemotherapy-induced cutaneous toxicity, can cause an alteration in fingerprints causing a setback for cancer patients due to the occurrence of false rejections. A colon cancer patient was fingerprinted after not having been able to use fingerprint recognition devices after 6 months of adjuvant chemotherapy. The fingerprint images were digitally processed to improve fingerprint definition without altering the papillary design. No evidence of skin toxicity was present. Two months later, the situation returned to normal. The fingerprint evaluation conducted on 15 identification points highlighted the quantitative and qualitative fingerprint alteration details detected after the end of chemotherapy and 2 months later. Fingerprint alteration during chemotherapy has been reported, but to our knowledge, this particular case is the first ever reported without evident clinical signs. Alternative fingerprint identification methods as well as improved biometric identification systems are needed in case of unexpected situations

Effects of the lockdown period on the mental health of elite athletes during the COVID-19 pandemic: a narrative review

none9Purpose This review aimed to assess the effects of COVID-19 pandemic lockdown on mental health to elite athletes. The emotional background influenced their sport career and was examined by questionnaires. Methods We included original studies that investigated psychological outcomes in elite athletes during COVID-19 lockdown. Sixteen original studies (n = 4475 participants) were analyzed. Results The findings showed that COVID-19 has an impact on elite athletes' mental health and was linked with stress, anxiety and psychological distress. The magnitude of the impact was associated with athletes' mood state profile, personality and resilience capacity. Conclusion The lockdown period impacted also elite athletes' mental health and training routines with augmented anxiety but with fewer consequences than the general population thanks to adequate emotion regulation and coping strategies.noneCarnevale Pellino, Vittoria; Lovecchio, Nicola; Puci, Mariangela V; Marin, Luca; Gatti, Alessandro; Pirazzi, Agnese; Negri, Francesca; Ferraro, Ottavia E; Vandoni, MatteoCarnevale Pellino, Vittoria; Lovecchio, Nicola; Puci, Mariangela V; Marin, Luca; Gatti, Alessandro; Pirazzi, Agnese; Negri, Francesca; Ferraro, Ottavia E; Vandoni, Matte

Second-line chemotherapy for advanced pancreatic cancer: Which is the best option?

Despite recent biological insight and therapeutic advances, the prognosis of advanced pancreatic cancer still remains poor. For more than 15 years, gemcitabine monotherapy has been the cornerstone of first-line treatment. Recently, prospective randomized trials have shown that novel upfront combination regimens tested in prospective randomized trials have resulted in improved patients' outcome increasing the proportion of putative candidate to second-line therapy. There is no definite standard of care after disease progression. A novel formulation in which irinotecan is encapsulated into liposomal-based nanoparticles may increase the efficacy of the drug without incrementing its toxicity. NAPOLI-1 was the first randomized trial to compare nanoliposomal irinotecan and fluorouracil-leucovorin (5-FU/LV) to 5-FU/LV alone after a gemcitabine-based chemotherapy. This review focuses on the current data for the management of second-line treatment for metastatic pancreatic adenocarcinoma, presents the most interesting ongoing clinical trials and illustrates the biologically-driven future options beyond disease progression

Thymidylate synthase, topoisomerase-1 and microsatellite instability: Relationship with outcome in mucinous colorectal cancer treated with fluorouracil

Background: Mucinous colorectal cancer (CRC) exhibits distinct clinical and pathological features, including poorer response to fluorouracil (FU) compared with non-mucinous tumours. Patients and Methods: We compared the expression of thymidylate synthase (TYMS) and topoisomerase-1 (TOPO1) and DNA microsatellite instability (MSI) in 87 patients (35 mucinous and 52 non-mucinous CRCs) enrolled in three randomized trials, evaluating infused FU as first-line treatment. Results: Mucinous CRCs more frequently had high TOPO1 expression than did non-mucinous tumors (41% vs. 15%, p=0.028). The median overall survival was 14.2 months for patients with mucinous CRC with low TOPO1 expression compared with 9.7 months for high TOPO1-expressing cases (p=0.016). After adjusting for confounding variables, low TOPO1 expression was statistically favourably associated with overall survival (hazard ratio=0.55; p=0.041). Conclusion: Our data suggest the TOPO1 expression levels to be a prognostic marker in patients with mucinous CRC treated with FU. If further verified, these data might redefine therapeutic strategies by identifying categories of patients with a worse prognosis

Expression of pERK and VEGFR-2 in advanced hepatocellular carcinoma and resistance to sorafenib treatment

Background & Aims: The study aimed to evaluate the tissue expression of molecules involved in intracellular signalling pathways as predictors of response to sorafenib in advanced hepatocellular carcinoma (HCC). Methods: We considered 77 patients enrolled into three prospective trials of sorafenib treatment for whom pretreatment tumour tissue was available. The tissue expression of \u3b2-catenin, glutamine synthetase (GS), phosphorylated extracellular signal regulated kinase (pERK), phosphorylated v-akt murine thymoma viral oncogene homolog (pAKT) and vascular endothelial growth factor receptor-2 (VEGFR-2) was analysed by immunostaining. Stains were scored semiquantitatively and compared with a reference group of 56 untreated HCCs. Results: Overall, the expression of antigens was comparable between treated and untreated patients. Shorter progression-free survival (PFS) and overall survival (OS) were associated with increased pERK staining ( 65 2+ scores) (PFS: 75th percentile 4.4 vs 8.4 months; P = 0.01; OS: 75th percentile 7.0 vs 15.0 months; P = 0.005) and VEGFR-2 staining ( 65 2+ scores) (PFS: 75th percentile 3.8 vs 7.0 months; P = 0.039; OS: 75th percentile 6.3 vs 15.0 months; P = 0.004). At multivariate analysis, both pERK and VEGFR-2 staining maintained an independent effect on OS (HR 2.09; 95% CI, 1.13-3.86, P = 0.019 and HR 2.28; 95% CI, 1.13-4.61, P = 0.021 respectively). No effect was observed for the other tested biomarkers. Conclusions: Elevated tissue expression of pERK and VEGFR-2 was predictive of poor outcome in advanced HCC treated with sorafenib

Second-line angiogenesis inhibition in metastatic colorectal cancer patients: Straightforward or overcrowded?

Although the number of therapeutic options targeting tumour angiogenesis is becoming increasingly relevant, the question of the optimal choice for second-line anti-angiogenic inhibition in combination with chemotherapy for metastatic colorectal cancer patients remains largely unanswered.In fact the lack of head to head comparison between consolidated options such as bevacizumab and new treatment alternatives such as aflibercept and ramucirumab makes the selection in the clinical practice challenging, particularly when the patient has already received an anti-angiogenic-based combination up-front.In the following pages we described the biological scenario validating second-line angiogenesis inhibition in colorectal cancer along with potential mechanism of resistance. We also critically described the available evidence recommending the use of the bevacizumab, aflibercept and ramucirumab in this setting with the final aim to guide the choice in the clinical practice