BACKGROUND:Extended mesocolic lymph node dissection in colon cancer surgery seems to improve oncological outcome. A possible reason might be related to metastases in the central mesocolic lymph ...nodes.
OBJECTIVE:The purpose of this study was to describe the pattern of mesocolic lymph node metastases, particularly in central lymph nodes, and the risk of skip, aberrant, and gastrocolic ligament metastases as the argument for performing extended lymph node dissection.
DATA SOURCES:EMBASE and PubMed were searched using the terms colon or colorectal with sentinel node, lymph node mapping, or skip node; lymph node resection colon; and complete or total and mesocolic excision.
STUDY SELECTION:Studies describing the risk of metastases in central, skip, aberrant, and gastrocolic ligament lymph node metastases from colon adenocarcinomas in 10 or more patients were included. No languages were excluded.
MAIN OUTCOME MEASURES:The risk of metastases in the central mesocolic lymph nodes was measured.
RESULTS:A total of 2052 articles were screened, of which 277 underwent full-text review. The 47 studies fulfilling the inclusion criteria were very heterogeneous, and meta-analyses were not considered appropriate. The risk of central mesocolic lymph node metastases for right-sided cancers varies between 1% and 22%. In sigmoid cancer, the risk is reported in ≤12% of the patients and is associated with advanced T stage.
LIMITATIONS:The retrospective design and heterogeneity, in terms of definitions of lymph node location, tumor sites, stage, morphology, pathology assessment, and inclusion criteria (selection bias), of the included studies were limitations. Also, anatomic definitions were not uniform.
CONCLUSIONS:The present literature cannot give a theoretical explanation of a better oncological outcome after extended lymph node dissection. Consensus for a standardization of anatomical definitions and surgical and pathological assessments is warranted for future mapping studies.
Relapse at the central nervous system (CNS) in acute myeloid leukemia (AML) carries a dismal prognosis. Treatment options are limited to intrathecal therapy, high-dose cytarabine, high-dose ...methotrexate, and radiotherapy. Novel strategies are needed. Venetoclax has recently been approved by the FDA, in combination with hypomethylating agents or low-dose cytarabine, for elderly adults or patients ineligible for intensive chemotherapy affected by AML. However, little is known on its efficacy in patients with leptomeningeal involvement. Here, we present a case of a 52-year-old patient affected by AML relapsed at CNS after allogeneic bone marrow transplantation who was treated with venetoclax. We evaluated the concentration of the drug in cerebrospinal fluid (CSF) by HPLC MS/MS method on three different occasions to verify the penetration of the drug through the brain–blood barrier and we observed that the concentration in CSF was similar to the IC50 established in vitro.
Purpose: To evaluate feasibility, toxicities, and clinical response in Stage IV patients treated with palliative “metabolism-guided” lattice technique. Patients and Methods: From June 2020 to ...December 2021, 30 consecutive clinical stage IV patients with 31 bulky lesions were included in this study. All patients received palliative irradiation consisting of a spatially fractionated high radiation dose delivered in spherical deposits (vertices, Vs) within the bulky disease. The Vs were placed at the edges of tumor areas with different metabolisms at the PET exam following a non-geometric arrangement. Precisely, the Vs overlapped the interfaces between the tumor areas of higher 18F-FDG uptake (>75% SUV max) and areas with lower 18F-FDG uptake. A median dose of 15 Gy/1 fraction (range 10−27 Gy in 1/3 fractions) was delivered to the Vs. Within 7 days after the Vs boost, all the gross tumor volume (GTV) was homogeneously treated with hypo-fractionated radiation therapy (RT). Results: The rate of symptomatic response was 100%, and it was observed immediately after lattice RT delivery in 3/30 patients, while 27/30 patients had a symptomatic response within 8 days from the end of GTV irradiation. Radiation-related acute grade ≥1 toxicities were observed in 6/30 (20%) patients. The rate of overall clinical response was 89%, including 23% of complete remission. The 1-year overall survival rate was 86.4%. Conclusions: “Metabolism-guided” lattice radiotherapy is feasible and well-tolerated, being able to yield very impressive results both in terms of symptom relief and overall clinical response rate in stage IV bulky disease patients. These preliminary results seem to indicate that this kind of therapy could emerge as the best therapeutic option for this patient setting.
The experience of third-generation tyrosine kinase inhibitor ponatinib treatment in Philadelphia chromosome-positive acute lymphoblastic leukaemia (Ph’+ ALL) patients post-allogeneic transplantation ...is limited. We retrospectively collected data on 25 Ph’+ ALL patients who were started on ponatinib after allogeneic transplantation between July 2015 and July 2019 from nine transplantation centers in Italy. Ponatinib was given in prophylaxis in five (20%), as pre-emptive treatment in seven (28%), and as salvage therapy in thirteen (52%) patients. It was combined with donor leukocyte infusions in ten patients. Half of the patients (12/25) harbored T315I mutation of
BCR/ABL1
, while in the remaining mutational analysis was negative or not performed. Among the 20 patients who received ponatinib as pre-emptive/salvage treatment, complete molecular response was achieved in 15 (75%) patients. Estimated overall survival at 2-year post-initiation of treatment in the whole cohort was 65% (respectively 60%, 60%, and 78% for the prophylaxis, pre-emptive, and salvage therapy groups). In patients with T315I-positive mutational status, the estimated 2-year survival was 40%. Fourteen patients (56%) experienced toxicity, requiring temporary or definitive suspension of treatment. In conclusion, treatment of Ph’+ ALL patients with ponatinib after transplantation is effective, although the question of adequate drug dose and treatment duration remains unanswered.
Blinatumomab is a bispecific anti-CD3 and anti-CD19 antibody that acts as a T-cell engager: by binding CD19+ lymphoblasts, blinatumomab recruits cytotoxic CD3+ T-lymphocytes to target the cancer ...cells. Here we describe seven different patients affected by B-cell precursor acute lymphoblastic leukemia (Bcp-ALL) and treated with blinatumomab, on which we evaluated the potential association between the amount of different T-cells subsets and deep molecular response after the first cycle, identified as a complete remission in the absence of minimal residual disease (CR/MRD). The immune-system effector cells studied were CD3+, CD4+ effector memory (T4-EM), CD8+ effector memory (T8-EM), and T-regulatory (T-reg) lymphocytes, and myeloid-derived suppressor cells (MDSC). Measurements were performed in the peripheral blood using flow cytometry of the peripheral blood at baseline and after the first cycle of blinatumomab. The first results show that patients with a higher proportion of baseline T-lymphocytes achieved MRD negativity more frequently with no statistically significant difference (p=0.06) and without differences in the subpopulation count following the first treatment. These extremely preliminary data could potentially pave the way for future studies, including larger and less heterogeneous cohorts, in order to assess the T-cell kinetics in a specific set of patients with potential synergy effects in targeting myeloid-derived suppressor cells (MDSC), commonly known to have an immune evasion mechanism in Bcp-ALL.
Endothelial dysfunction (ED) is frequently encountered in transplant medicine. ED is an argument of high complexity, and its understanding requires a wide spectrum of knowledge based on many fields ...of basic sciences such as molecular biology, immunology, and pathology. After hematopoietic stem cell transplantation (HSCT), ED participates in the pathogenesis of various complications such as sinusoidal obstruction syndrome/veno-occlusive disease (SOS/VOD), graft-versus-host disease (GVHD), transplant-associated thrombotic microangiopathy (TA-TMA), idiopathic pneumonia syndrome (IPS), capillary leak syndrome (CLS), and engraftment syndrome (ES). In the first part of the present manuscript, we briefly review some biological aspects of factors involved in ED: adhesion molecules, cytokines, Toll-like receptors, complement, angiopoietin-1, angiopoietin-2, thrombomodulin, high-mobility group B-1 protein, nitric oxide, glycocalyx, coagulation cascade. In the second part, we review the abnormalities of these factors found in the ED complications associated with HSCT. In the third part, a review of agents used in the treatment of ED after HSCT is presented.
Purpose
To evaluate the role of stereotactic body radiation therapy (SBRT) delivered after external-beam fractionated irradiation in non-small-cell lung cancer (NSCLC) patients with clinical stage ...III A, B.
Materials and methods
All patients received three-dimensional conformal radiotherapy (3D-CRT) or intensity modulated radiation therapy (IMRT) (60–66 Gy/30–33 fractions of 2 Gy/5 days a week) with or without concomitant chemotherapy. Within 60 days from the end of irradiation, a SBRT boost (12–22 Gy in 1–3 fractions) was delivered on the residual disease.
Results
Here we report the mature results of 23 patients homogeneously treated and followed up for a median time of 5.35 years (range 4.16–10.16). The rate of overall clinical response after external beam and stereotactic boost was 100%. No treatment-related mortality was recorded. Radiation-related acute toxicities with a grade ≥ 2 were observed in 6/23 patients (26.1%): 4/23 (17.4%) had esophagitis with mild esophageal pain (G2); in 2/23 (8.7%) clinical radiation pneumonitis G2 was observed. Lung fibrosis (20/23 patients, 86.95%) represented a typical late tissue damage, which was symptomatic in one patient. Median disease-free survival (DFS) and overall survival (OS) were 27.8 (95% CI, 4.2–51.3) and 56.7 months (95% CI, 34.9–78.5), respectively. Median local progression-free survival (PFS) was 17 months (range 11.6–22.4), with a median distant PFS of 18 months (range 9.6–26.4). The 5-year actuarial DFS and OS rates were 28.7% and 35.2%, respectively.
Conclusions
We confirm that a stereotactic boost after radical irradiation is feasible in stage III NSCLC patients. All fit patients who have no indication to adjuvant immunotherapy and presenting residual disease after curative irradiation could benefit from stereotactic boost because outcomes seem to be better than might be historically assumed.
Despite effective treatments, cytomegalovirus (CMV) continues to have a significant impact on morbidity and mortality in allogeneic stem cell transplant (allo-SCT) recipients. This multicenter, ...retrospective, cohort study aimed to evaluate the reproducibility of the safety and efficacy of commercially available letermovir for CMV prophylaxis in a real-world setting. Endpoints were rates of clinically significant CMV infection (CSCI), defined as CMV disease or CMV viremia reactivation within day +100-+168. 204 adult CMV-seropositive allo-SCT recipients from 17 Italian centres (median age 52 years) were treated with LET 240 mg/day between day 0 and day +28. Overall, 28.9% of patients underwent a haploidentical, 32.4% a matched related, and 27.5% a matched unrelated donor (MUD) transplant. 65.7% were considered at high risk of CSCI and 65.2% had a CMV seropositive donor. Low to mild severe adverse events were observed in 40.7% of patients during treatment gastrointestinal toxicity (36.3%) and skin rash (10.3%). Cumulative incidence of CSCI at day +100 and day +168 was 5.4% and 18.1%, respectively, whereas the Kaplan-Meier event rate was 5.8% (95% CI: 2.4-9.1) and 23.3% (95% CI: 16.3-29.7), respectively. Overall mortality was 6.4% at day +100 and 7.3% at day +168. This real-world experience confirms the efficacy and safety of CMV.
Ruxolitinib is a JAK1/2 inhibitor that has revolutionized the approach to myelofibrosis. On the one side, this drug can rapidly improve the symptoms related to the hematological disease; on the other ...side, the inhibition of JAK1/2 can lead to immunosuppression which may increase the risk of infections, due to a change in the cytokine balance in favor of anti-inflammatory cytokines, to direct inhibition of immune cells, and to the suppression in the production of specific antibodies. In this patient setting, much is known about possible viral and bacterial infections, while little is reported in the literature concerning parasitic infections, specifically leishmaniasis.
is a parasitic infection that can cause serious problems in immunosuppressed patients. The parasite can invade the bloodstream and cause a wide range of symptoms, including fever, weight loss, and anemia. In severe cases, it can lead to multi-organ failure and, rapidly, death. Early diagnosis and prompt treatment are essential especially for these patients, unable to respond adequately. In this case and the following review of the existing literature, the cytokine kinetics and the production of specific anti-
antibodies represent characteristic aspects capable of providing a more in-depth understanding of the mechanisms underlying these complex clinical cases in an immunocompromised patient.
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