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1.
Gastric Cancer ; 25(6): 1105-1116, 2022 11.
Article in English | MEDLINE | ID: mdl-35864239

ABSTRACT

BACKGROUND: Oncologic outcomes after laparoscopic gastrectomy for advanced gastric cancer in the West have been poorly investigated. The aim of the present study was to compare survival outcomes in patients undergoing curative-intent laparoscopic and open gastrectomy for advanced gastric cancer in several centres belonging to the Italian Research Group for Gastric Cancer. METHODS: Data of patients operated between 2015 and 2018 were retrospectively analysed. Propensity Score Matching was performed to balance baseline characteristics of patients undergoing laparoscopic and open gastrectomy. The primary endpoint was 3-year overall survival. Secondary endpoints were 3-year disease-free survival and short-term outcomes. Multivariable regression analyses for survival were conducted. RESULTS: Data were retrieved from 20 centres. Of the 717 patients included, 438 patients were correctly matched, 219 per group. The 3-year overall survival was 73.6% and 68.7% in the laparoscopic and open group, respectively (p = 0.40). When compared with open gastrectomy, laparoscopic gastrectomy showed comparable 3-year disease-free survival (62.8%, vs 58.9%, p = 0.40), higher rate of return to intended oncologic treatment (56.9% vs 40.2%, p = 0.001), similar 30-day morbidity/mortality. Prognostic factors for survival were ASA Score ≥ 3, age-adjusted Charlson Comorbidity Index ≥ 5, lymph node ratio ≥ 0.15, p/ypTNM Stage III and return to intended oncologic treatment. CONCLUSIONS: Laparoscopic gastrectomy for advanced gastric cancer offers similar rates of survival when compared to open gastrectomy, with higher rates of return to intended oncologic treatment. ASA score, age-adjusted Charlson Comorbidity Index, lymph node ratio, return to intended oncologic treatment and p/ypTNM Stage, but not surgical approach, are prognostic factors for survival.


Subject(s)
Adenocarcinoma , Laparoscopy , Stomach Neoplasms , Humans , Stomach Neoplasms/pathology , Propensity Score , Retrospective Studies , Adenocarcinoma/pathology , Treatment Outcome , Gastrectomy/adverse effects , Laparoscopy/adverse effects
2.
J Transl Med ; 18(1): 340, 2020 09 03.
Article in English | MEDLINE | ID: mdl-32883314

ABSTRACT

BACKGROUND: Duodenal adenocarcinoma (DA) is a rare yet aggressive malignancy, with increasing incidence in the last decades. Its low frequency has hampered a thorough understanding of the pathogenesis of the disease and of its biology, limiting the identification of tailored therapeutic options. A large body of evidence has clearly shown the clinical relevance of immune cells in solid tumors, correlating immune features with post-surgical prognosis. The aim of this study was to analyze the immune contexture in a cohort of duodenal adenocarcinomas surgically resected at our Institution and define its correlation with clinical variables. METHODS: Tissue slides from paraffin-embedded tumor specimens of 15 consecutive DA and 3 adenomas that underwent a pancreaticoduodenectomy in our center between 2010 to 2018 were immunohistochemically stained. The density (percentage of immune reactive area, IRA%) of immune markers CD45RO, CD8, CD20, IL-17, PD-1, CD68 was quantified by computer-assisted image analysis. Demographic, clinical, histopathological data were collected. RESULTS: In our population, median IRA % (IQR) of immune subsets was respectively CD45RO-TILs 2.19 (2.14), CD8-TIL 0.42 (0.81), CD20-TILs 0.22 (0.51), CD20-TLT 2.84 (4.64), CD68-TAM 2.19 (1.56), IL17+ cells 0.39 (0.39), PD1-TILs 0.19 (0.41). The median follow-up was 47.5 (22.4-63.3) months. At statistical analysis, the density of CD8-TILs inversely correlated with lymph node ratio (p = 0.013), number of metastatic lymph nodes (p = 0.019), and was lower in N+ adenocarcinomas compared to N0 (1.07 vs 0.29; p = 0.093), albeit not significantly. Stratifying patients for the N status, the density of CD8-TILs decreased with the increasing of the N stage (p = 0.065) and was lower in patients who experienced recurrence and died for the disease (0.276 vs 0.641; p = 0.044). Notably, also CD68-TAM distribution was different in patients who had recurrence versus patients who did not (1.028 vs 2.276; p = 0.036). CONCLUSIONS: Immune cells showed variable expression in correlation with common prognostic factors, suggesting T cell infiltration may play a protective role towards lymphatic spread of disease and nodal metastatization. Furthermore, T cell density and macrophage infiltration were associated to a lower risk of recurrence and disease related death. A multicentric approach may be indicated to allow analysis of larger cohorts of patients, potentially increasing the power of our observations.


Subject(s)
Lymphocytes, Tumor-Infiltrating , Neoplasm Recurrence, Local , Biomarkers , Humans , Leukocyte Common Antigens , Prognosis
3.
Hematol Oncol ; 36(2): 381-391, 2018 Apr.
Article in English | MEDLINE | ID: mdl-28660653

ABSTRACT

Cytomegalovirus (CMV) infection in clinical settings other than the allogeneic transplant represents a poorly explored issue. Thus, we performed a comprehensive review of the medical literature about CMV infection in patients undergoing autologous hematopoietic stem cell transplant and in other nontransplant-related hematologic patients. In autologous hematopoietic stem cell transplant, a CMV reactivation is reported to occur in up to 41% of CMV seropositive patients, when a prospective monitoring of antigenemia and/or viremia by polymerase chain reaction was adopted. However, more contained frequencies, up to 12%, have been reported when the monitoring criteria were based on a clinically driven diagnostic strategy. The most relevant risk factors appear to be CD34 + selected autografts, total body irradiation, and prior treatment with Alemtuzumab, Fludarabine, or Bortezomib, respectively. Other possible risk factors (ie, prior treatment with Rituximab, T-cell lymphomas, and pretransplant HBcIgG seropositivity) are still debated. In nontransplant settings, the data are very heterogeneous; thus, CMV infection incidence and risk factors are more difficult to establish. Overall, the rate of CMV infection/reactivation ranges between 2 and 67%. High-dose steroids, advanced disease, poor performance status, and treatment with Alemtuzumab, Fludarabine, Bortezomib, and Rituximab appear as the most relevant, though putative, risk factors. Intravenous Ganciclovir represents the gold standard for first-line treatment of CMV infection in these patients. Oral Valganciclovir and Foscarnet are other possible options. Extensive prophylaxis and preemptive therapy are not generally recommended, with the exception of high-risk patients.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Cytomegalovirus Infections/diagnosis , Hematologic Neoplasms/therapy , Hematopoietic Stem Cell Transplantation/methods , Antiviral Agents/therapeutic use , Combined Modality Therapy , Cytomegalovirus Infections/complications , Cytomegalovirus Infections/drug therapy , Ganciclovir/therapeutic use , Hematologic Neoplasms/complications , Humans , Transplantation, Homologous , Virus Activation/drug effects
4.
Ann Hematol ; 97(9): 1717-1726, 2018 Sep.
Article in English | MEDLINE | ID: mdl-29705860

ABSTRACT

Infections by multidrug-resistant (MDR) bacteria are a worrisome phenomenon in hematological patients. Data on the incidence of MDR colonization and related bloodstream infections (BSIs) in haematological patients are scarce. A multicentric prospective observational study was planned in 18 haematological institutions during a 6-month period. All patients showing MDR rectal colonization as well as occurrence of BSI at admission were recorded. One-hundred forty-four patients with MDR colonization were observed (6.5% of 2226 admissions). Extended spectrum beta-lactamase (ESBL)-producing (ESBL-P) enterobacteria were observed in 64/144 patients, carbapenem-resistant (CR) Gram-negative bacteria in 85/144 and vancomycin-resistant enterococci (VREs) in 9/144. Overall, 37 MDR-colonized patients (25.7%) developed at least one BSI; 23 of them (62.2%, 16% of the whole series) developed BSI by the same pathogen (MDRrel BSI), with a rate of 15.6% (10/64) for ESBL-P enterobacteria, 14.1% (12/85) for CR Gram-negative bacteria and 11.1% (1/9) for VRE. In 20/23 cases, MDRrel BSI occurred during neutropenia. After a median follow-up of 80 days, 18 patients died (12.5%). The 3-month overall survival was significantly lower for patients colonized with CR Gram-negative bacteria (83.6%) and VRE (77.8%) in comparison with those colonized with ESBL-P enterobacteria (96.8%). CR-rel BSI and the presence of a urinary catheter were independent predictors of mortality. MDR rectal colonization occurs in 6.5% of haematological inpatients and predicts a 16% probability of MDRrel BSI, particularly during neutropenia, as well as a higher probability of unfavourable outcomes in CR-rel BSIs. Tailored empiric antibiotic treatment should be decided on the basis of colonization.


Subject(s)
Bacteremia/epidemiology , Bacterial Infections/epidemiology , Drug Resistance, Multiple, Bacterial , Hematologic Neoplasms/complications , Hematologic Neoplasms/epidemiology , Adolescent , Adult , Aged , Aged, 80 and over , Bacteremia/microbiology , Bacterial Infections/blood , Bacterial Infections/complications , Bacterial Infections/microbiology , Catheter-Related Infections/epidemiology , Child , Child, Preschool , Female , Hematologic Neoplasms/microbiology , Humans , Infant , Infant, Newborn , Male , Middle Aged , Young Adult
6.
Ann Ig ; 29(5): 440-452, 2017.
Article in English | MEDLINE | ID: mdl-28715057

ABSTRACT

PURPOSE: Morbid obesity is associated with several comorbidities that often impair patients' ability to obtain and keep a job and that, eventually, could hinder their fitness to work. This study aimed at determining whether the employment status of morbidly obese patients may be positively affected by bariatric surgery. METHODS: A total of 30 morbidly obese patients who underwent Roux-en-Y gastric bypass (RYGB) from March 2014 to March 2015 were prospectively evaluated. All patients underwent a pre-operative assessment including the collection of personal and occupational data and the evaluation of musculoskeletal system. All evaluations were repeated at the end of a 24-month follow up. RESULTS: After RYGB, employment rates increased from 15/30 (50.0%) to 25/30 (83.3%, p = 0.012). Patients who were working at the end of follow-up referred lower rates of comorbidities, in particular of musculoskeletal complaints (4/25 vs. 4/5, p < 0.001), and presented significantly increased scores of energy/vitality at SF-36 assessment. CONCLUSIONS: Our study suggests that RYGB can increase employment rates, increasing tolerance to effort and reducing prevalence and severity of obesity-related symptoms and complaints.


Subject(s)
Employment/statistics & numerical data , Gastric Bypass , Obesity, Morbid/surgery , Adult , Cohort Studies , Comorbidity , Follow-Up Studies , Humans , Male , Middle Aged , Prospective Studies
7.
Support Care Cancer ; 24(9): 3839-45, 2016 09.
Article in English | MEDLINE | ID: mdl-27075673

ABSTRACT

PURPOSE: Chronic disseminated candidiasis (CDC) is a complication of Candida infection in immunocompromised patients, involving the liver and spleen, and rarely other organs. The aim of the study is to identify the best antifungal drug for hematologic immunocompromised patients with CDC. METHODS: In this multicentric retrospective study, the charts of 20 patients with CDC following cytotoxic agent protocols for hematological malignancies, diagnosed from 2003 to 2013, were analyzed. The response to systemic antifungal therapy within 90 days from CDC diagnosis and the possible delay in chemotherapy plan, due to the infection, were evaluated. RESULTS: Six patients were treated with high-dose (HD; 5 mg/kg/daily) liposomal amphotericin B (L-AmB), whereas three received standard-dose (SD) L-AmB (3 mg/kg/daily). Azoles were given to six patients; the remaining five were treated with echinocandins. All patients treated with HD L-AmB (6/6-100 %) achieved complete resolution of CDC; one of them had to interrupt the chemotherapy program for the infection. In the SD L-AmB group, treatment failed in the 100 % of cases and one patient had to delay chemotherapy for the infection. Of the six patients who received azoles, two achieved complete resolution of the infection, four experienced treatment failure, and only three performed chemotherapy as planned. Echinocandins treatment resulted in complete resolution of the infection in 2/5 cases, partial response in 2/5 cases, and failure in one case. In this group, 3/5 patients completed chemotherapy as planned. CONCLUSIONS: This study shows that HD L-AmB was particularly effective against CDC in hematologic patients, allowing most patients to continue cytotoxic agent program.


Subject(s)
Amphotericin B/therapeutic use , Antifungal Agents/administration & dosage , Antifungal Agents/therapeutic use , Candidiasis/drug therapy , Hematologic Neoplasms/complications , Adult , Amphotericin B/administration & dosage , Candidiasis/etiology , Female , Hematologic Neoplasms/drug therapy , Humans , Immunocompromised Host , Male , Middle Aged , Retrospective Studies , Young Adult
8.
Vet Pathol ; 53(2): 477-92, 2016 Mar.
Article in English | MEDLINE | ID: mdl-26467077

ABSTRACT

The 129 mouse strain is commonly used for the generation of genetically engineered mice. Genetic drift or accidental contamination during outcrossing has resulted in several 129 substrains. Comprehensive data on spontaneous age-related pathology exist for the 129S4/SvJae substrain, whereas only limited information is available for other 129 substrains. This longitudinal aging study describes the life span and spontaneous lesions of 44 male and 18 female mice of the 129S6/SvEvTac substrain. Median survival time was 778 and 770 days for males and females, respectively. Tumors of lung and Harderian gland were the most common neoplasms in both sexes. Hepatocellular tumors occurred mainly in males. Hematopoietic tumors were observed at low frequency. Suppurative and ulcerative blepharoconjunctivitis was the most common nonneoplastic condition in both sexes. Corynebacteria (primarily Corynebacterium urealyticum and C. pseudodiphtheriticum) were isolated from animals with blepharoconjunctivitis and in some cases from unaffected mice, although a clear causal association between corynebacterial infections and blepharoconjunctivitis could not be inferred. Polyarteritis occurred only in males and was identified as the most common nonneoplastic contributory cause of death. Eosinophilic crystalline pneumonia occurred in both sexes and was a relevant cause of death or comorbidity. Epithelial hyalinosis at extrapulmonary sites was noted at higher frequency in females. This study contributes important data on the spontaneous age-related pathology of the 129S6/SvEvTac mouse substrain and is a valuable reference for evaluation of the phenotype in genetically engineered mice obtained with this 129 substrain.


Subject(s)
Aging/pathology , Neoplasms/pathology , Animals , Female , Longevity , Longitudinal Studies , Male , Mice , Mice, Inbred Strains , Models, Animal , Morbidity , Mortality , Neoplasms/mortality , Phenotype
9.
Vet Pathol ; 52(4): 696-9, 2015 Jul.
Article in English | MEDLINE | ID: mdl-25161208

ABSTRACT

A 4-year old spayed male domestic shorthair cat was presented with a history of circling and behavioral changes. Neurologic examination showed mild proprioceptive deficits. The lesion was localized in the forebrain, and magnetic resonance imaging revealed the presence of a large midline intracranial mass extending from the frontal lobe to the tentorial region of the brain. Euthanasia was elected due to poor prognosis. Histopathologic evaluation confirmed the presence of a mass composed by sheets and aggregates of large round/polygonal cells and multinucleate cells associated with deposits of cholesterol clefts, scattered hemorrhages and hemosiderin-laden macrophages. Immunohistochemistry showed that the round/polygonal cells and multinucleate cells were strongly positive for major histocompatibility complex class II antigen, variably positive for CD18, and occasionally positive for S100. Subsets of spindle cells showing variable expression of vimentin, S100, and neuron-specific enolase were also present. The final diagnosis was cholesterol granuloma. Differential diagnosis with meningioma is discussed.


Subject(s)
Cat Diseases/pathology , Granuloma/veterinary , Meningeal Neoplasms/veterinary , Meningioma/veterinary , Animals , Behavior, Animal , Brain/pathology , Cats , Granuloma/pathology , Immunohistochemistry/veterinary , Magnetic Resonance Imaging/veterinary , Male , Meningeal Neoplasms/pathology , Meningioma/pathology , Phosphopyruvate Hydratase/metabolism
10.
Transpl Infect Dis ; 16(6): 1032-8, 2014 Dec.
Article in English | MEDLINE | ID: mdl-25369809

ABSTRACT

The introduction of proteasome inhibitors and/or immunomodulators in the treatment of myeloma has led to an increase in viral infections, particularly in the Herpesviridae family. Previous studies about the risk of cytomegalovirus (CMV) reactivation after autologous stem cell transplantation (ASCT) have examined the clinical outcome after the first ASCT; however, only 1 study to date has investigated the risk of CMV reactivation after a second transplantation. To address this issue, we performed a retrospective chart review on 78 consecutive myeloma patients (median age 56 years) who underwent a tandem non-CD34(+) selected ASCT after induction treatment with either conventional chemotherapy (n = 42) or with novel agents (n = 36), respectively. All subjects had been mobilized and conditioned with cyclophosphamide plus granulocyte colony-stimulating factor and melphalan alone, respectively. CMV DNA load in the blood has been determined by polymerase chain reaction in the case of a clinical suspicion of CMV reactivation; therefore, routine monitoring was not performed. Considering the outcome of both the first and the second transplantations, we observed a total of 13 episodes of symptomatic CMV reactivation (13/156, 8%), in 12 subjects (12/78, 15%), all successfully treated. Eight subjects experienced a CMV reactivation after the first ASCT (8/78, 10%); however, only 1 of them (1/8, 12%) experienced a CMV reactivation after the second transplantation. Conversely, 4 CMV reactivations (6%) were observed after the second transplantation in the group of 70 patients who did not experience a CMV reactivation after the first ASCT. No statistically significant difference was observed between first and second ASCT (8/78, 10% vs. 5/78, 6%; P = 0.767). Univariate analysis showed that a pre-transplant treatment with novel agents was the only baseline factor significantly associated with the occurrence of post-ASCT CMV symptomatic reactivation after the first transplant (odds ratio [OR]: 9.897; 95% confidence interval [CI]: 1.154-84.840; P = 0.021) but not after the second transplant (OR: 5.125; 95% CI: 0.546-48.119; P = 0.115). No end-organ disease or primary infection was documented. Our data suggest that second transplantation does not increase the risk of CMV reactivation in our patient population, when compared with the first one, and confirm the role of a pre-transplant treatment with novel agents as a risk factor for CMV symptomatic reactivation.


Subject(s)
Boronic Acids/therapeutic use , Cytomegalovirus Infections/pathology , Multiple Myeloma/therapy , Pyrazines/therapeutic use , Stem Cell Transplantation , Adult , Aged , Antineoplastic Agents/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Boronic Acids/administration & dosage , Bortezomib , Dexamethasone/administration & dosage , Dexamethasone/therapeutic use , Doxorubicin/administration & dosage , Doxorubicin/therapeutic use , Female , Humans , Immunologic Factors/administration & dosage , Immunologic Factors/therapeutic use , Male , Middle Aged , Pyrazines/administration & dosage , Retrospective Studies , Risk Factors , Vincristine/administration & dosage , Vincristine/therapeutic use
11.
Transpl Infect Dis ; 16(1): 158-64, 2014 Feb.
Article in English | MEDLINE | ID: mdl-24215479

ABSTRACT

The incidence of cytomegalovirus (CMV) reactivations in patients with multiple myeloma (MM) receiving autologous stem cell transplantation (ASCT) is relatively low. However, the recent increased use of novel agents, such as bortezomib and/or immunomodulators, before transplant, has led to an increasing incidence of Herpesviridae family virus infections. The aim of the study was to establish the incidence of post-engraftment symptomatic CMV reactivations in MM patients receiving ASCT, and to compare this incidence with that of patients treated with novel agents or with conventional chemotherapy before transplant. The study was a survey of 80 consecutive patients who underwent ASCT after treatment with novel agents (Group A). These patients were compared with a cohort of 89 patients treated with VAD regimen (vincristine, doxorubicin, and dexamethasone) before ASCT (Group B). Overall, 7 patients (4.1%) received an antiviral treatment for a symptomatic CMV reactivation and 1 died. The incidence of CMV reactivations was significantly higher in Group A than in Group B (7.5% vs. 1.1%; P = 0.048). When compared with Group B, the CMV reactivations observed in Group A were significantly more frequent in patients who received bortezomib, whether or not associated with immunomodulators (9.4% vs. 1.1%; P = 0.019), but not in those treated with immunomodulators only (3.7% vs. 1.1%; P = 0.396). These results suggest that MM patients treated with bortezomib-based regimens are at higher risk of developing a symptomatic CMV reactivation after ASCT.


Subject(s)
Antineoplastic Agents/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Boronic Acids/therapeutic use , Cytomegalovirus Infections/epidemiology , Immunocompromised Host , Multiple Myeloma/therapy , Pyrazines/therapeutic use , Stem Cell Transplantation , Adult , Aged , Bortezomib , Case-Control Studies , Cohort Studies , Cytomegalovirus Infections/immunology , Dexamethasone/therapeutic use , Doxorubicin/therapeutic use , Humans , Incidence , Induction Chemotherapy , Middle Aged , Retrospective Studies , Risk Factors , Transplantation, Autologous , Vincristine/therapeutic use
13.
Br J Cancer ; 109(9): 2424-33, 2013 Oct 29.
Article in English | MEDLINE | ID: mdl-24084767

ABSTRACT

BACKGROUND: In pancreatic ductal adenocarcinoma (PDAC), fractalkine receptor CX3CR1 contributes to perineural invasion (PNI). We investigated whether CX3CR1 expression occurs early in PDAC and correlates with tumour features other than PNI. METHODS: We studied CX3CR1 and CX3CL1 expression by immunohistochemistry in 104 human PDAC and coexisting Pancreatic Intraepithelial Neoplasia (PanIN), and in PdxCre/LSL-Kras(G12D) mouse model of PDAC. CX3CR1 expression in vitro was studied by a spheroid model, and in vivo by syngenic mouse graft of tumour cells. RESULTS: In total, 56 (53.9%) PDAC expressed CX3CR1, 70 (67.3%) CX3CL1, and 45 (43.3%) both. CX3CR1 expression was independently associated with tumour glandular differentiation (P=0.005) and PNI (P=0.01). Pancreatic Intraepithelial Neoplasias were more frequently CX3CR1+ (80.3%, P<0.001) and CX3CL1+ (86.8%, P=0.002) than matched cancers. The survival of PDAC patients was better in those with CX3CR1+ tumour (P=0.05). Mouse PanINs were also CX3CR1(+) and -CL1(+). In vitro, cytokines significantly increased CX3CL1 but not CX3CR1 expression. Differently, CX3CR1 was upregulated in tumour spheroids, and in vivo only in well-differentiated tumours. CONCLUSION: Tumour differentiation, rather than inflammatory signalling, modulates CX3CR1 expression in PanINs and PDAC. CX3CR1 expression pattern suggests its early involvement in PDAC progression, outlining a potential target for interfering with the PanIN transition to invasive cancer.


Subject(s)
Carcinogenesis/metabolism , Pancreatic Neoplasms/metabolism , Receptors, Chemokine/biosynthesis , Animals , CX3C Chemokine Receptor 1 , Carcinogenesis/genetics , Carcinoma, Pancreatic Ductal/genetics , Carcinoma, Pancreatic Ductal/metabolism , Carcinoma, Pancreatic Ductal/pathology , Cell Differentiation/physiology , Cell Line, Tumor , Chemokine CX3CL1/biosynthesis , Chemokine CX3CL1/genetics , Disease Models, Animal , Female , Humans , Male , Mice , Mice, Inbred C57BL , Pancreatic Neoplasms/genetics , Pancreatic Neoplasms/pathology , Receptors, Chemokine/genetics , Retrospective Studies , Up-Regulation
14.
Leukemia ; 37(12): 2383-2394, 2023 12.
Article in English | MEDLINE | ID: mdl-37803061

ABSTRACT

Extramedullary (EM) colonization is a rare complication of acute myeloid leukemia (AML), occurring in about 10% of patients, but the processes underlying tissue invasion are not entirely characterized. Through the application of RNAseq technology, we examined the transcriptome profile of 13 AMLs, 9 of whom presented an EM localization. Our analysis revealed significant deregulation within the extracellular matrix (ECM)-receptor interaction and focal-adhesion pathways, specifically in the EM sites. The transcription factor TWIST1, which is known to impact on cancer invasion by dysregulating epithelial-mesenchymal-transition (EMT) processes, was significantly upregulated in EM-AML. To test the functional impact of TWIST1 overexpression, we treated OCI-AML3s with TWIST1-siRNA or metformin, a drug known to inhibit tumor progression in cancer models. After 48 h, we showed downregulation of TWIST1, and of the EMT-related genes FN1 and SNAI2. This was associated with significant impairment of migration and invasion processes by Boyden chamber assays. Our study shed light on the molecular mechanisms associated with EM tissue invasion in AML, and on the ability of metformin to interfere with key players of this process. TWIST1 may configure as candidate marker of EM-AML progression, and inhibition of EMT-pathways may represent an innovative therapeutic intervention to prevent or treat this complication.


Subject(s)
Leukemia, Myeloid, Acute , Metformin , Humans , Cell Line, Tumor , Epithelial-Mesenchymal Transition/genetics , Leukemia, Myeloid, Acute/genetics , Leukemia, Myeloid, Acute/pathology , RNA, Small Interfering , Neoplasm Invasiveness/pathology , Gene Expression Regulation, Neoplastic
15.
Ann R Coll Surg Engl ; 104(7): e208-e210, 2022 Jul.
Article in English | MEDLINE | ID: mdl-35442821

ABSTRACT

The optimal surgical procedure for Siewert II oesophagogastric junction cancer is still debated. The minimally invasive Ivor Lewis technique can be considered the most adequate intervention from the oncological perspective but it is still contested owing to its technical difficulties. To allow an easier thoracoscopic stage during the procedure, we performed it with laparoscopic trans-hiatal oesophageal transection and transabdominal extraction. An 80-year-old man with stage 3 Siewert II oesophagogastric junction adenocarcinoma not suitable for neoadjuvant therapy underwent minimally invasive Ivor Lewis oesophagectomy with two-field lymphadenectomy, using a laparoscopic and thoracoscopic approach in prone position. The trans-hiatal oesophageal resection permitted easy extraction of a transabdominal specimen and frozen section examination. The prone position, together with the absence of the specimen in the operative field, allowed easier mediastinal node dissection and oesophagogastric anastomosis with better visualisation. The postoperative course was uneventful. Pathology showed a G3-pT3, N2 adenocarcinoma with 6/30 metastatic lymph nodes.


Subject(s)
Adenocarcinoma , Esophageal Neoplasms , Laparoscopy , Adenocarcinoma/pathology , Adenocarcinoma/surgery , Aged, 80 and over , Esophageal Neoplasms/diagnosis , Esophagectomy/methods , Esophagogastric Junction/pathology , Esophagogastric Junction/surgery , Humans , Laparoscopy/methods , Male , Retrospective Studies
16.
Ann R Coll Surg Engl ; 103(1): e4-e6, 2021 Jan.
Article in English | MEDLINE | ID: mdl-32820640

ABSTRACT

In the past few years, minimally invasive oesophagectomy has become an increasingly popular approach for oesophagectomy showing advantages in terms of fewer postoperative complications, shorter hospital stay and faster recovery. We present the case of a 60-year-old man with a lesion of the distal third of the oesophagus and solid pulmonary nodule who underwent McKeown subtotal oesophagectomy by laparoscopic and thoracoscopic approach in prone position with concomitant thoracoscopic pulmonary wedge resection. The postoperative course was smooth, and the patient was discharged on postoperative day 10. The procedure is feasible and safe, and combines better respiratory postoperative outcomes even when associated with other diagnostic or therapeutic lung procedures.


Subject(s)
Esophageal Neoplasms/surgery , Esophagectomy/methods , Laparoscopy/methods , Lung Neoplasms/surgery , Pneumonectomy/methods , Thoracoscopy/methods , Biopsy , Combined Modality Therapy/adverse effects , Combined Modality Therapy/methods , Esophageal Neoplasms/diagnosis , Esophageal Neoplasms/pathology , Esophagectomy/adverse effects , Esophagus/diagnostic imaging , Esophagus/pathology , Esophagus/surgery , Feasibility Studies , Humans , Laparoscopy/adverse effects , Lung/diagnostic imaging , Lung/pathology , Lung/surgery , Lung Neoplasms/diagnosis , Lung Neoplasms/secondary , Male , Middle Aged , Patient Positioning/adverse effects , Patient Positioning/methods , Pneumonectomy/adverse effects , Prone Position , Thoracoscopy/adverse effects , Tomography, X-Ray Computed , Treatment Outcome
17.
J Anal Toxicol ; 45(9): 918-926, 2021 Nov 09.
Article in English | MEDLINE | ID: mdl-33031554

ABSTRACT

The scientific interest in cannabis has been documented by a wide literature, but postmortem studies and interpretations of autopsy findings are lacking or limited to few cases, few matrices analyzed or a small number of analytes. The present study describes the development and full in-house validation of a sensitive and simple method based on an optimized rapid clean-up procedure combined with a robust and highly sensitive liquid chromatography coupled with tandem mass spectrometry (LC-MS-MS) technique, designed to simultaneous determination of Δ9-tetrahydrocannabinol (THC), cannabidiol (CBD), 11-hydroxy-Δ9-tetrahydrocannabinol (11-OH-THC), 11-nor-Δ9-tetrahydrocannabinol-carboxylic acid (THC-COOH) and 11-nor-Δ9-tetrahydrocannabinol-carboxylic acid glucuronated (THC-COOH gluc.) in postmortem samples: central blood (CB), femoral blood (FB) and brain tissue (BR). The developed method was validated and applied to 24 postmortem cases involving cannabinoids. In this study, we presented a full optimization and validation of target analyses for each matrix. The procedure had proven to be reliable and accurate. This study adds new data, particularly about the cannabinoids concentrations in BR samples. Combined pattern (CB, FB, BR) can be used in the interpretation of postmortem cases, proving and strengthening the assessments made on blood data. BR matrix is a helpful supplement in the investigation of the role of cannabinoids as crucial or contributory factor in leading to death.


Subject(s)
Cannabinoids , Autopsy , Brain , Dronabinol , Tandem Mass Spectrometry
18.
Ann R Coll Surg Engl ; 102(6): e130-e132, 2020 Jul.
Article in English | MEDLINE | ID: mdl-32326737

ABSTRACT

Minimally invasive oesophagectomy has become popular, but studies showed a higher rate of postoperative hiatus hernia compared with open oesophagectomy. Our video presents the laparoscopic biosynthetic mesh repair of a symptomatic giant hiatus hernia in a 71-year-old man who had undergone minimally invasive oesophagectomy one year earlier for distal adenocarcinoma of the oesophagus. The operative time was 120 minutes. The patient started oral intake on postoperative day one and was discharged on postoperative day three. Postoperative computed tomography at six months showed no signs of recurrence. In the setting of a symptomatic hiatus hernia post-minimally invasive oesophagectomy, we suggest an initial laparoscopic approach, because of its countless advantages.


Subject(s)
Esophagectomy/adverse effects , Hernia, Hiatal/surgery , Herniorrhaphy/methods , Laparoscopy/methods , Postoperative Complications/surgery , Thoracoscopy/adverse effects , Adenocarcinoma/therapy , Aged , Chemoradiotherapy, Adjuvant , Colon, Transverse/diagnostic imaging , Diaphragm/diagnostic imaging , Diaphragm/surgery , Esophageal Neoplasms/therapy , Hernia, Hiatal/diagnosis , Hernia, Hiatal/etiology , Herniorrhaphy/instrumentation , Humans , Intestine, Small/diagnostic imaging , Laparoscopy/instrumentation , Male , Neoadjuvant Therapy , Patient Readmission , Postoperative Complications/diagnosis , Postoperative Complications/etiology , Surgical Mesh , Suture Techniques , Tomography, X-Ray Computed , Treatment Outcome
19.
Vet Pathol ; 46(6): 1301-5, 2009 Nov.
Article in English | MEDLINE | ID: mdl-19605917

ABSTRACT

A 22-week-old female 129/SvEv mouse suddenly died in the context of an experiment aimed at defining the efficacy of valproic acid in a mouse model of PML/RARalpha-induced acute myeloid leukemia. Histologic analysis confirmed the mouse as being affected by a progressive myeloid leukemia, with infiltration of the spleen, bone marrow, liver, kidneys, and lungs. Variably sized intravascular clumps (emboli) of dense basophilic material admixed with necrotic or lytic neoplastic cells were also observed in multiple organs. A positive reaction to Feulgen and Hoechst stain confirmed the high content in chromatin of these basophilic emboli. Cleaved caspase-3 activity was demonstrated both in the leukemic infiltrates and among the intravascular necrotic or lytic neoplastic cells accompanying the basophilic emboli. A diagnosis of acute tumor lysis syndrome related to therapy-induced massive necrosis and/or apoptosis of leukemic cells with subsequent dissemination of emboli of chromatin was proposed.


Subject(s)
Leukemia, Myeloid, Acute/chemically induced , Tumor Lysis Syndrome/veterinary , Acute Disease , Animals , Antineoplastic Agents/pharmacology , Death, Sudden , Disease Models, Animal , Female , Lung/pathology , Mice , Tumor Lysis Syndrome/pathology , Valproic Acid/pharmacology
20.
Ann R Coll Surg Engl ; 101(2): e45-e47, 2019 Feb.
Article in English | MEDLINE | ID: mdl-30354179

ABSTRACT

The incidence of biliary lithiasis after gastric surgery seems to be higher than in the general population. Endoscopic retrograde cholangiopancreatography (ERCP) allows several biliary and pancreatic pathologies to be dealt with; however, in patients with an altered anatomy of the upper and mid gastrointestinal tract, this endoscopic manoeuvre can be extremely challenging. We report a case of a 79-year-old woman with previous subtotal gastrectomy and Roux-en-Y reconstruction, admitted with a diagnosis of cholecystitis and choledocolithiasis. She was successfully treated with transjejunal laparoscopic-assisted ERCP and laparoscopic cholecystectomy, which appears to be a safe and useful procedure for choledocolithiasis treatment in patients with surgically altered anatomy.


Subject(s)
Cholangiopancreatography, Endoscopic Retrograde/methods , Cholecystectomy, Laparoscopic/methods , Cholecystitis/surgery , Choledocholithiasis/surgery , Gastrectomy , Jejunum/surgery , Postoperative Complications/surgery , Aged , Anastomosis, Roux-en-Y , Cholecystitis/etiology , Choledocholithiasis/etiology , Female , Humans
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