Second-line treatment of diffuse large B-cell lymphoma: Evolution of options.

In the era of immunochemotherapy, approximately 60%-70% of diffuse large B-cell lymphoma (DLBCL) patients achieve remission with first-line rituximab-based chemoimmunotherapy. However, 30%-40% relapse after initial response to first-line therapy and, out of them, 20%-50% are refractory or experience early relapse. The second-line therapy algorithm for DLBCL has recently evolved, thanks to the recent approval of new therapeutic agents or their combinations. The new guidelines suggest a stratification of relapsed/refractory (R/R) DLBCL based on the time to relapse. For transplant-eligible patients, autologous stem cell transplant remains the preferred option when the patient relapses after 12 months from diagnosis, while anti-CD19 CART-cell therapy is the current preferred choice for high-risk DLBCL, defined as primary refractory or relapse ≤12 months. For transplant-ineligible or CAR T-cell therapy-ineligible patients, the therapeutic arsenal historically lacked effective options. However, new therapeutic options, including polatuzumab vedotin combined with bendamustine-rituximab and tafasitamab with lenalidomide, have been recently approved, and novel agents such as loncastuximab tesirine, selinexor, anti-CD19 CAR T-cell therapy, and bispecific antibodies have shown promising efficacy and manageable safety in this setting offering new hope to patients in this challenging scenario.

Swab test in biological fluids as predictor of COVID-19 transmission risk during surgery: a prospective cross-sectional study from an Italian COVID center.

BACKGROUND: The contamination of body fluids by Severe Acute Respiratory Syndrome Coronavirus 2 during surgery is current matter of debate in the scientific literature concerning CoronaVIrus Disease 2019. Surgical guidelines were published during the first wave of the COVID-19 pandemic and recommended to avoid laparoscopic surgery as much as possible, in fear that the chimney effect of high flow intraperitoneal gas escape during, and after, the procedure would increase the risk of viral transmission. AIM: The aim of this study was to evaluate the possibility of SARS-CoV-2 transmission during surgery by searching for viral RNA in serial samplings of biological liquids. METHODS: This is a single center prospective cross-sectional study. We used a real-time reverse transcriptase (RT) polymerase chain reaction (PCR) test to perform swab tests for the qualitative detection of nucleic acid from SARS-CoV-2 in abdominal fluids, during emergency surgery and on the first post-operative day. In the case of thoracic surgery, we performed a swab test of pleural fluids during chest drainage placement as well as on the first post-operative day. RESULTS: A total of 20 samples were obtained: 5 from pleural fluids, 13 from peritoneal fluids and two from biliary fluid. All 20 swabs performed from biological fluids resulted negative for SARS-CoV-2 RNA detection. CONCLUSION: To date, there is no scientific evidence of possible contagion by laparoscopic aerosolization of SARS-CoV-2, neither is certain whether the virus is effectively present in biological fluids.

COVID-19: identifying the main outcome predictors. A retrospective cohort study in Northern Italy.

OBJECTIVE: The need for efficient drugs and early treatment of patients with SARS-CoV-2 infection developing COVID-19 symptoms is of primary importance in daily clinical practice and it is certainly among the most difficult medical challenges in the current century. Recognizing those patients who will need stronger clinical efforts could effectively help doctors anticipate the eventual need for intensification of care (IoC) and choose the best treatment in order to avoid worse outcomes. PATIENTS AND METHODS: We enrolled 501 patients, consecutively admitted to our two COVID hospitals, and collected their clinical, anamnestic and laboratory data on admission. The aim of this retrospective study was to identify those data that are strictly associated with COVID-19 outcomes (IoC and in-hospital death) and that could somehow be intended as predictors of these outcomes. This allowed us to provide a "sketch" of the patient who undergoes, more often than others, an intensification of care and/or in-hospital death. RESULTS: Males were found to have a double risk of needing an IoC (OR=2.11) and a significant role was played by both the PaO2/FiO2 ratio on admission (OR=0.99) and serum LDH (OR=1.01). The main predictors of in-hospital death were age (OR=1.08) and the PaO2/FiO2 ratio on admission (OR=0.99). CONCLUSIONS: Male patients with high serum LDH on admission are those who undergo more often an intensification of care among COVID-19 inpatients. Both age and respiratory performances on admission modify the prognosis within the hospitalization period.

SARS-CoV-2 infection and H1N1 vaccination: does a relationship between the two factors really exist? A retrospective analysis of a territorial cohort in Ferrara, Italy.

OBJECTIVE: SARS-CoV-2 has been compared with other strains of coronaviruses, SARS-CoV and MERS-CoV, and with the flu viruses: all of them manifest themselves with respiratory symptoms and, although their genetic patterns are similar, the spread of SARS-CoV-2 infection has quickly reached global dimensions, demonstrating that SARS-CoV-2 is a virus with greater spreading capacity, albeit less lethal. Compared with influenza viruses, coronaviruses have a longer incubation period and the patients with coronaviruses' syndromes develop more severe diseases requiring frequent hospitalizations and intensive care admissions. The aim was to explore the relationships between seasonal influenza vaccination and coronavirus infection and to understand whether this hypothetic role by the flu vaccines modifies SARS-CoV-2 infection's outcomes. PATIENTS AND METHODS: In this retrospective, multicenter study, we enrolled 952 patients diagnosed with SARS-CoV-2 infection; 448 were admitted to our two main hospitals in Ferrara territory, while the remaining 504 were isolated at home. We compared the group of patients who had been vaccinated for influenza in the previous 12 months to that of unvaccinated patients. RESULTS: Significant differences were found for both the need for hospitalization and 30-day mortality between vaccinated and unvaccinated patients. We found age to be the only independent risk factor for a worse 30-day prognosis, while gender, influenza vaccinations and age itself were independent risk factors for undergoing hospitalization. CONCLUSIONS: In our groups of patients, we found a relationship between seasonal influenza vaccinations and SARS-CoV-2 infection. Age seems to be the main risk factor for short-term mortality in COVID-19 inpatients, while the influenza vaccination is, together with gender and age itself, a determining factor in predicting the need for hospitalization.

The sacral chordoma margin.

OBJECTIVE: Aim of the manuscript is to discuss how to improve margins in sacral chordoma. BACKGROUND: Chordoma is a rare neoplasm, arising in half cases from the sacrum, with reported local failure in >50% after surgery. METHODS: A multidisciplinary meeting of the "Chordoma Global Consensus Group" was held in Milan in 2017, focusing on challenges in defining and achieving optimal margins in chordoma with respect to surgery, definitive particle radiation therapy (RT) and medical therapies. This review aims to report on the outcome of the consensus meeting and to provide a summary of the most recent evidence in this field. Possible new ways forward, including on-going international clinical studies, are discussed. RESULTS: En-bloc tumor-sacrum resection is the cornerstone of treatment of primary sacral chordoma, aiming to achieve negative microscopic margins. Radical definitive particle therapy seems to offer a similar outcome compared to surgery, although confirmation in comparative trials is lacking; besides there is still a certain degree of technical variability across institutions, corresponding to different fields of treatment and different tumor coverage. To address some of these questions, a prospective, randomized international study comparing surgery versus definitive high-dose RT is ongoing. Available data do not support the routine use of any medical therapy as (neo)adjuvant/cytoreductive treatment. CONCLUSION: Given the significant influence of margins status on local control in patients with primary localized sacral chordoma, the clear definition of adequate margins and a standard local approach across institutions for both surgery and particle RT is vital for improving the management of these patients.

Treatment of Colorectal Cancer: a Multidisciplinary Approach.

BACKGROUND: Colorectal cancer is the third most prevalent cancer in the world, preceded by prostate and lung cancers in men (10%) and breast and lung cancers in women (9.4%). Colorectal cancer is the fourth leading cause of death in men (7.6%) and the third in women (8.6%). A multidisciplinary approach has radically changed the way we deal with this disease among all specialist fields. PURPOSE: In this study, we propose comparing the multidisciplinary experience group (started in 2012) of S. Anna Hospital (University of Ferrara) with the previous approach to rectal cancer before the advent of the multidisciplinary program. RESULTS: We find that more study depth of neoplastic disease as well as of each individual patient leads to more accurate staging and to a weighted therapy based on the needs of the individual. All the studies were performed in accordance with the guidelines established by the European and Italian associations.

Laparoscopic resection of a jejunal mesenteric pseudocyst: case report.

Mesenteric cysts are rare and can occur at any age. They can manifest with abdominal pain or compressive mass effect. The exact etiology is unknown. Ultrasonography, computed tomography and laparoscopy are used in diagnosing mesenteric cysts. Laparoscopic excision of a mesenteric cyst is possible and should be considered as the treatment of choice. We present a case of mesenteric pseudocyst of small bowel treated by laparoscopic excision.

Totally laparoscopic resection of a very large gastric GIST.

Laparoscopic approach was safely performed for the diagnosis and treatment of the submucosal tumors of the stomach because it is associated with low morbidity, mortality, and sound oncologic outcomes. However, no report on the long-term safety and efficacy of this surgery for large sized gastric GISTs has been published to date. We present a 63-year-old female case of a large gastric GIST of 19 cm removed by laparoscopic wedge resection.

Spatial entanglement of bosons in optical lattices.

Entanglement is a fundamental resource for quantum information processing, occurring naturally in many-body systems at low temperatures. The presence of entanglement and, in particular, its scaling with the size of system partitions underlies the complexity of quantum many-body states. The quantitative estimation of entanglement in many-body systems represents a major challenge, as it requires either full-state tomography, scaling exponentially in the system size, or the assumption of unverified system characteristics such as its Hamiltonian or temperature. Here we adopt recently developed approaches for the determination of rigorous lower entanglement bounds from readily accessible measurements and apply them in an experiment of ultracold interacting bosons in optical lattices of ~10(5) sites. We then study the behaviour of spatial entanglement between the sites when crossing the superfluid-Mott insulator transition and when varying temperature. This constitutes the first rigorous experimental large-scale entanglement quantification in a scalable quantum simulator.

Quasiparticle dynamics in a bose insulator probed by interband bragg spectroscopy.

We investigate experimentally and theoretically the dynamical properties of a Mott insulator in decoupled one-dimensional chains. Using a theoretical analysis of the Bragg excitation scheme, we show that the spectrum of interband transitions holds information on the single-particle Green's function of the insulator. In particular, the existence of particle-hole coherence due to quantum fluctuations in the Mott state is clearly seen in the Bragg spectra and quantified. Finally, we propose a scheme to directly measure the full, momentum-resolved spectral function as obtained in the angle-resolved photoemission spectroscopy of solids.

Severe osteolysis and soft tissue mass around total hip arthroplasty: description of four cases and review of the literature with respect to clinico-radiographic and pathologic differential diagnosis.

Periprosthetic osteolysis is a well known phenomenon caused by wear particle-induced bone resorption, particularly common and extensively reported in total hip arthroplasty. Its typical radiographic feature is a radiolucent area adjacent to an implant, sometimes associated with a soft tissue mass. Osteolytic changes may be caused by numerous other pathologic processes, including infection, metabolic disease, and neoplasia. Four cases of massive periprosthetic bone destruction associated with a large soft tissue mass around a failed total hip replacement are presented. In three cases, a diagnosis of periprosthetic osteolysis was correctly made and managed by revision surgery. However, in one case angiosarcoma of the ipsilateral hemipelvis went long unrecognized despite aggressive clinical course, requiring hind-quarter amputation and ultimately resulting in the patient's death. Periprosthetic malignancy in the form of either primary sarcoma or metastatic cancer is a very rare yet reported event in the setting of previous hip replacement, likely leading to catastrophic consequences when diagnosis is not established in a timely manner. The differential diagnosis of periprosthetic osteolysis should consider the entire spectrum of conditions that can present with radiolucent changes. Thorough review of patient's history and course of symptoms, along with careful evaluation of standard roentgenograms should be always performed and possibly integrated with imaging modalities such as CT, MRI, and bone scintigraphy in order to increase diagnostic accuracy. If uncertainty remains, biopsy should always be considered to rule out malignancy.

Exploring correlated 1D bose gases from the superfluid to the mott-insulator state by inelastic light scattering.

We report the Bragg spectroscopy of interacting one-dimensional Bose gases loaded in an optical lattice across the superfluid to the Mott-insulator phase transition. Elementary excitations are created with a nonzero momentum and the response of the correlated 1D gases is in the linear regime. The complexity of the strongly correlated quantum phases is directly displayed in the spectra which exhibit novel features. This work paves the way for a precise characterization of the state of correlated gases in optical lattices.

Noise correlation spectroscopy of the broken order of a Mott insulating phase.

We use a two-color lattice to break the homogeneous site occupation of an atomic Mott insulator of bosonic 87Rb. We detect the disruption of the ordered Mott domains via noise correlation analysis of the atomic density distribution after time of flight. The appearance of additional correlation peaks evidences the redistribution of the atoms into a strongly inhomogeneous insulating state, in quantitative agreement with the predictions.

Ewing's sarcoma family tumours. Differences in clinicopathological characteristics at presentation between localised and metastatic tumours.

Despite local treatment with systemic chemotherapy in Ewing's sarcoma family tumours (ESFT), patients with detectable metastases at presentation have a markedly worse prognosis than those with apparently localised disease. We investigated the clinical, pathological and laboratory differences in 888 patients with ESFT, 702 with localised disease and 186 with overt metastases at presentation, seen at our institution between 1983 and 2006. Multivariate analyses showed that location in the pelvis, a high level of serum lactic dehydrogenase, the presence of fever and a short interval between the onset of symptoms and diagnosis were indicative of metastatic disease. The rate of overt metastases at presentation was 10% without these four risk factors, 22.7% with one, 31.4% with two, and 50% for those with three or four factors. We concluded that in ESFT the site, the serum level of lactic dehydrogenase, fever, and the interval between the onset of symptoms and diagnosis are indicators of tumours having a particularly aggressive metastatic behaviour.

Treatment and prognosis for synchronous multifocal osteosarcoma in 42 patients.

Between 1986 and 2002, 42 patients with synchronous multifocal osteosarcoma were treated with two different protocols of neoadjuvant chemotherapy. When feasible, the primary and secondary tumours were excised as a combined procedure. After initial chemotherapy 26 patients were excluded from simultaneous excision of all their secondary bone lesions as their disease was too advanced. In 12 patients only isolated excision of the primary lesion was possible. For 16 patients simultaneous operations were conducted to excise the primary and secondary lesions. This involved two supplementary sites in 15 patients and four additional sites in one patient. Of these, 15 attained remission but 12 relapsed and died (11 within two years). Three patients remained disease-free at five, six and 17 years. The histological response to pre-operative chemotherapy of the primary and secondary lesions was concordant in 13 of the 16 patients who underwent simultaneous operations at more than one site. The prognosis for synchronous multifocal osteosarcoma remains poor despite combined chemotherapy and surgery. The homogeneous histological responses in a large proportion of the primary and secondary lesions implies that synchronous multifocal osteosarcoma tumours are not multicentric in origin, but probably represent bone-to-bone metastases from a single tumour.

[Cancer of the right colon: biological features and extent of the surgical resection]. / Il cancro del colon destro: aspetti biologici ed ampiezza della resezione chirurgica.

Right-sided colon cancer therapy is based upon right hemicolectomy, which is a well established surgical technique. Considering the possibility of biological diversity in cancer arising from the caecum, ascending colon and transverse colon, this retrospective study analysed age, sex, grading, T, N, M and mortality to evaluate the biological characteristics of the cancers and their level of local and general diffusion with a view to establishing any correlation between these characteristics and the advisability of employing different surgical procedures for the different sites. Cancer arising from the sites considered does not seem to present different biological aspects and therefore a different surgical procedure is not authorized. Our data show that a significant majority of cancers are diagnosed at an advanced stage as compared to earlier stages (P < 0.05) and that early detection of these cancers is the best way of improving the prognosis.

Neoadjuvant chemotherapy for patients with synchronous multifocal osteosarcoma: results in eleven cases.

Between January 1995 and December 1999, 11 patients with synchronous multifocal osteosarcoma (SMO) received neoadjuvant treatment with high-dose methotrexate, cisplatinum, Adriamycin, and ifosfamide. After primary chemotherapy in 4 patients who had only two bone localizations, it was possible to treat all tumor foci locally. The remaining patients, with more than three bones involved, were treated surgically only in 3 cases at the primary site, while secondary lesions did not receive any treatment. The final results of our study were disappointing. All patients died of the tumor 6 to 24 months after the beginning of treatment (mean 11.9 months). Nevertheless, the survival time of the 4 patients with locally treated lesions was significantly longer than the one of 7 patients in whom the secondary lesions were not locally treated (18.2 vs 9.1 months; P<0.008). It should be noted that those patients simultaneously operated on two sites, the response to chemotherapy of "primary" and "secondary" lesions was always similar. This homogeneity supports the thesis that in synchronous multifocal osteosarcoma the tumors are not multicentric in origin but represent bone-to-bone metastases from a monocentric tumor.

Telangiectatic osteosarcoma of the extremity: neoadjuvant chemotherapy in 24 cases.

Between April 1990 and December 1994, we treated 24 patients with telangiectatic osteosarcoma (TO) of the extremities with neoadjuvant chemotherapy using 2 protocols. Surgery consisted of limb salvage in 21 patients and amputation or rotation plasty in 3. The histologic response to chemotherapy was good (90% or more tumor necrosis) in 23 patients, of whom 12 had total necrosis. With a mean follow-up of 74 (60-96) months, 20 patients remained continuously free of disease and 4 relapsed with lung metastases. There were no local recurrences. Comparing these results to the ones achieved in 269 contemporary patients with conventional osteosarcoma of the extremities using the same protocols for chemotherapy, we found a significantly better histologic response to chemotherapy (96% vs 68% of good histologic response; p = 0.004) and disease-free survival (83% vs 55%; p = 0.01) in the TO group. We conclude that TO, once considered a lethal tumor, seems to be even more sensitive to chemotherapy than conventional osteosarcoma, and that most of these patients may be cured without amputation.