A first-in-class Wiskott-Aldrich syndrome protein activator with anti-tumor activity in hematologic cancers.

Hematological cancers are among the most common cancers in adults and children. Despite significant improvements in therapies, many patients still succumb to the disease. Therefore, novel therapies are needed. The Wiskott-Aldrich syndrome protein (WASp) family regulates actin assembly in conjunction with the Arp2/3 complex, a ubiquitous nucleation factor. WASp is expressed exclusively in hematopoietic cells and exists in two allosteric conformations: autoinhibited or activated. Here, we describe the development of EG-011, a first-in-class small molecule activator of the WASp auto-inhibited form. EG-011 possesses in vitro and in vivo anti-tumor activity as a single agent in lymphoma, leukemia, and multiple myeloma, including models of secondary resistance to PI3K, BTK, and proteasome inhibitors. The in vitro activity was confirmed in a lymphoma xenograft. Actin polymerization and WASp binding was demonstrated using multiple techniques. Transcriptome analysis highlighted homology with drugs-inducing actin polymerization.

Characterisation of CCT271850, a selective, oral and potent MPS1 inhibitor, used to directly measure in vivo MPS1 inhibition vs therapeutic efficacy.

BACKGROUND: The main role of the cell cycle is to enable error-free DNA replication, chromosome segregation and cytokinesis. One of the best characterised checkpoint pathways is the spindle assembly checkpoint, which prevents anaphase onset until the appropriate attachment and tension across kinetochores is achieved. MPS1 kinase activity is essential for the activation of the spindle assembly checkpoint and has been shown to be deregulated in human tumours with chromosomal instability and aneuploidy. Therefore, MPS1 inhibition represents an attractive strategy to target cancers. METHODS: To evaluate CCT271850 cellular potency, two specific antibodies that recognise the activation sites of MPS1 were used and its antiproliferative activity was determined in 91 human cancer cell lines. DLD1 cells with induced GFP-MPS1 and HCT116 cells were used in in vivo studies to directly measure MPS1 inhibition and efficacy of CCT271850 treatment. RESULTS: CCT271850 selectively and potently inhibits MPS1 kinase activity in biochemical and cellular assays and in in vivo models. Mechanistically, tumour cells treated with CCT271850 acquire aberrant numbers of chromosomes and the majority of cells divide their chromosomes without proper alignment because of abrogation of the mitotic checkpoint, leading to cell death. We demonstrated a moderate level of efficacy of CCT271850 as a single agent in a human colorectal carcinoma xenograft model. CONCLUSIONS: CCT271850 is a potent, selective and orally bioavailable MPS1 kinase inhibitor. On the basis of in vivo pharmacodynamic vs efficacy relationships, we predict that more than 80% inhibition of MPS1 activity for at least 24 h is required to achieve tumour stasis or regression by CCT271850.

Pentraxin 3 and Platelet Activation in Obese Patients After Gastric Banding.

BACKGROUND: Circulating pentraxin 3 (PTX3), the main regulator of the inflammatory response, rapidly increases following cardiovascular events, and low PTX3 is associated with high body mass index. METHODS AND RESULTS: We conducted a 12-month longitudinal study, to test the hypothesis that laparoscopic adjustable gastric banding (LAGB)-induced weight loss was associated with changes in platelet activation markers and PTX3. Twelve obese patients, scheduled to undergo LAGB, were enrolled at the University Obesity Center. Urinary 11-dehydro-thromboxane (Tx)B2excretion rate was measured on radioimmunoassay, and PTX3 and CD40L were determined on immunoassay. Plasma PTX3 increased by 178.8 and 214.9% (P<0.0001), respectively, 6 and 12 months after LAGB. High-sensitivity CRP decreased by 24 and 29.7% (P<0.0001), whereas CD40L decreased by 64.3 and 58.6% (P=0.002), respectively. Urinary 11-dehydro-TxB2decreased from 1,443 to 715 and 564 pg/mg creatinine, respectively 6 months and 12 months after LAGB (P<0.0001). PTX3 was inversely related to platelet activation markers, 11-dehydro-TxB2and CD40L. Moreover, multiple regression analysis on pooled data showed that plasma PTX3 was an independent predictor of urinary 11-dehydro-TxB2. CONCLUSIONS: There is an association between inflammation, platelet activation and metabolic dysfunction in obesity, and PTX3 is a key player within these circuits.

Expanding the scope of fused pyrimidines as kinase inhibitor scaffolds: synthesis and modification of pyrido[3,4-d]pyrimidines.

Fused pyrimidine cores are privileged kinase scaffolds, yet few examples of the 2-amino-pyrido[3,4-d]pyrimidine chemotype have been disclosed in the context of kinase inhibitor programs. Furthermore, no general synthetic route has been reported to access 2-amino-pyrido[3,4-d]pyrimidine derivatives. Here we report a versatile and efficient chemical approach to this class of molecules. Our strategy involves the concise preparation of 8-chloro-2-(methylthio)pyrido[3,4-d]pyrimidine intermediates and their efficient derivatisation to give novel compounds with potential as kinase inhibitors.

Combined derivatization and high-performance liquid chromatography with fluorescence and ultraviolet detection for simultaneous analysis of octreotide and gabexate mesylate metabolite in human pancreatic juice samples.

A simple and sensitive method based on the combination of derivatization and high-performance liquid chromatography with ultraviolet and fluorimetric detection was developed for the simultaneous determination of octreotide and gabexate mesylate metabolite in human pancreatic juice samples. Parameters of the derivatization procedure affecting extraction efficiency were optimized. The developed method was validated according to the International Conference on Harmonization guidelines. The calibration curves were linear over a range of 0.1-15 µg/mL for octreotide and 0.20-15 µg/mL for gabexate mesylate metabolite. Derivatized products of octreotide and gabexate mesylate metabolite were separated on a Luna C18 column (4.6 × 250 mm; 5 µm particle size) using a gradient with a run time of 36 min, without further purification. The limits of detection were 0.025 and 0.05, respectively, for octreotide and gabexate mesylate metabolite. This paper reports the validation of a quantitative high performance liquid chromatography-photodiode array-fluorescence (HPLC-PDA-FL) method for the simultaneous analysis of octreotide and gabexate mesylate metabolite in pancreatic juice by protein precipitation using zinc sulfate-methanol-acetonitrile containing the derivatizing reagent, 4-fluoro-7-nitro-[2,1,3]-benzoxadiazole (NBD-F). Derivatized products of octreotide and gabexate mesylate metabolite were separated on a Luna C18 column (4.6 × 250 mm; 5 µm particle size) using a gradient with a run time of 36 min, without further purification. The method was validated over the concentration ranges 0.1-15 and 0.2-15 µg/mL for octreotide and gabexate mesylate metabolite, respectively, in human pancreatic juice. Biphalin and methyl-p-hydroxybenzoate were used as the internal standards. This method was successfully utilized to support clinical studies in humans. The results from assay validations show that the method is selective, sensitive and robust. The limit of quantification of the method was 0.1 µg/mL for octreotide and 0.2 µg/mL for gabexate mesylate metabolite, and matrix matched standard curves showed a good linearity up to 15 µg/mL. In the entire analytical range the intra- and inter-day precision (RSD%) values were respectively ≤5.9% and ≤3.1% for octreotide and ≤2.0% and ≤3.9% for gabexate mesylate metabolite. For both analytes the intra- and inter-day accuracy (bias) values ranged respectively from -6.8 to -2.5% and from -4.6 to -5.7%. This method utilizes derivatization with NBD-F and provides adequate sensitivity for both drugs.

Radiochemotherapy in Anal Cancer: cCR, clinical outcomes and quality of life using two different treatment schedules.

AIM: Main endpoint was a response rate to therapy; secondary endpoints were disease-free survival, overall survival, acute and late toxicities, specially in terms of anorectal and urinary continence. BACKGROUND: Radiochemotherapy for anal cancer achieves a good clinical response, locoregional control, anal function preservation. However, oncologic outcomes can differ using radiotherapy plus fluorouracil and mytomicin vs. cisplatin and fluorouracil. METHODS: Between 2000 and 2012, 27 anal cancer patients receiving radiotherapy combined with two different radiochemotherapy schedules, fluorouracil and mytomicin (group A) and cisplatin plus fluorouracil (group B). The Kaplan-Meier method was also used to estimate local control, overall survival and disease free survival. Statistical significance between curves was evaluated using the Log-rank test. RESULTS: Complete pathological response was found in 85.2% of patients, with higher rates of response in the group A (100% vs. 63.6%, p = 0.039). No significantly difference was found between the two groups for the other endpoints. Low rates of both acute and late toxicities were recorded. CONCLUSION: Radiotherapy plus fluorouracil and mytomicin provide a better complete pathological response than radiotherapy plus cisplatin and fluorouracil and a greater rate of anal sphincter function preservation. Globally, radiochemotherapy of the anal cancer provides excellent clinical outcomes with a good profile of acute and late toxicity, without difference between the two groups studied.

Female responses to experimental removal of sexual selection components in Drosophila melanogaster.

BACKGROUND: Despite the common assumption that multiple mating should in general be favored in males, but not in females, to date there is no consensus on the general impact of multiple mating on female fitness. Notably, very little is known about the genetic and physiological features underlying the female response to sexual selection pressures. By combining an experimental evolution approach with genomic techniques, we investigated the effects of single and multiple matings on female fecundity and gene expression. We experimentally manipulated the opportunity for mating in replicate populations of Drosophila melanogaster by removing components of sexual selection, with the aim of testing differences in short term post-mating effects of females evolved under different mating strategies. RESULTS: We show that monogamous females suffer decreased fecundity, a decrease that was partially recovered by experimentally reversing the selection pressure back to the ancestral state. The post-mating gene expression profiles of monogamous females differ significantly from promiscuous females, involving 9% of the genes tested (approximately 6% of total genes in D. melanogaster). These transcripts are active in several tissues, mainly ovaries, neural tissues and midgut, and are involved in metabolic processes, reproduction and signaling pathways. CONCLUSIONS: Our results demonstrate how the female post-mating response can evolve under different mating systems, and provide novel insights into the genes targeted by sexual selection in females, by identifying a list of candidate genes responsible for the decrease in female fecundity in the absence of promiscuity.

Interspecific divergence of transcription networks along lines of genetic variance in Drosophila: dimensionality, evolvability, and constraint.

Change in gene expression is a major facilitator of phenotypic evolution. Understanding the evolutionary potential of gene expression requires taking into account complex systems of regulatory networks, the structure of which could potentially bias evolutionary trajectories. We analyzed the evolutionary potential and divergence of multigene expression in three well-characterized signaling pathways in Drosophila, the mitogen-activated protein kinase (MapK), the Toll, and the insulin receptor/Foxo (InR/Foxo or InR/TOR) pathways in a multivariate quantitative genetic framework. Gene expression data from a natural population of D. melanogaster were used to estimate the genetic variance-covariance matrices (G) for each network. Although most genes within each pathway exhibited significant genetic variance, the number of independent dimensions of multivariate genetic variance was fewer than the number of genes analyzed. However, for expression, the reduction in dimensionality was not as large as seen for other trait types such as morphology. We then tested whether gene expression divergence between D. melanogaster and an additional six species of the Drosophila genus was biased along the major axes of standing variation observed in D. melanogaster. In many cases, divergence was restricted to directions of phenotypic space harboring above average levels of genetic variance in D. melanogaster, indicating that genetic covariances between genes within pathways have biased interspecific divergence. We tested whether co-expression of genes in both sexes has also biased the pattern of divergence. Including cross-sex genetic covariances increased the degree to which divergence was biased along major axes of genetic variance, suggesting that the co-expression of genes in males and females can generate further constraints on divergence across the Drosophila phylogeny. In contrast to patterns seen for morphological traits in vertebrates, transcriptional constraints do not appear to break down as divergence time between species increases, instead they persist over tens of millions of years of divergence.

Diffuse large B-cell lymphoma of the colon with synchronous liver metastasis: a rare case report mimicking metastatic colorectal adenocarcinoma.

BACKGROUND: Primary colorectal lymphoma represents a rare minority among the colonic neoplasms. Early diagnosis is often difficult because of unspecific symptoms, with subsequent delays in diagnosis and management. We describe a rare case of colonic lymphoma presenting with synchronous liver metastasis. CASE PRESENTATION: A 70-year-old male with a 6-mo history of vague abdominal pain, constipation and melena was referred to our hospital. Computed tomography scan of abdomen revealed the presence of a mass along the proximal ascending colon. Colonoscopy biopsy showed external compression of the cecum with two ulcerations of mucosa, but it was not consistent for a definitive diagnosis. Because the difficulties in the preoperative pathological diagnosis, the high risk of bowel obstruction and the correlated hemorrhagic risk, the patient underwent a right hemicolectomy associated with locoregional lymphadenectomy and liver resection.The surgically resected right colon and liver tumors were all immunohistochemically diagnosed as diffuse large B-cell lymphomas (DLBCL). The patient refused any other antineoplastic treatment; he is alive and free of disease at 3 years after initial diagnosis. CONCLUSIONS: Primary colonic lymphomas represent a rare minority among the colonic neoplasms. Their correct pre-operative identification is crucial for the design of treatment. This case highlights the difficulty in diagnosing of primary colonic lymphoma. To our knowledge, this is the first report of a colonic lymphoma presenting with a colonic mass and a synchronous liver metastasis.

Synthesis and evaluation of carbapenem/metallo-ß-lactamase inhibitor conjugates.

Antibiotics, particularly the ß-lactams, are a cornerstone of modern medicine. However, the rise of bacterial resistance to these agents, particularly through the actions of ß-lactamases, poses a significant threat to our continued ability to effectively treat infections. Metallo-ß-lactamases (MBLs) are of particular concern due to their ability to hydrolyze a wide range of ß-lactam antibiotics including carbapenems. For this reason there is growing interest in the development of MBL inhibitors as well as novel antibiotics that can overcome MBL-mediated resistance. Here, we report the synthesis and evaluation of novel conjugates that combine a carbapenem (meropenem or ertapenem) with a recently reported MBL inhibiting indole carboxylate scaffold. These hybrids were found to display potent inhibition against MBLs including NDM-1 and IMP-1, with IC50 values in the low nanomolar range. However, their antibacterial potency was limited. Mechanistic studies suggest that despite maintaining effective MBL inhibiting activity in live bacteria, the new carbapenem/MBL inhibitor conjugates have a reduced ability to engage with the bacterial target of the ß-lactams.

Polyester degradation by soil bacteria: identification of conserved BHETase enzymes in Streptomyces.

The rising use of plastic results in an appalling amount of waste which is scattered into the environment. One of these plastics is PET which is mainly used for bottles. We have identified and characterized an esterase from Streptomyces, annotated as LipA, which can efficiently degrade the PET-derived oligomer BHET. The Streptomyces coelicolor ScLipA enzyme exhibits varying sequence similarity to several BHETase/PETase enzymes, including IsPETase, TfCut2, LCC, PET40 and PET46. Of 96 Streptomyces strains, 18% were able to degrade BHET via one of three variants of LipA, named ScLipA, S2LipA and S92LipA. SclipA was deleted from S. coelicolor resulting in reduced BHET degradation. Overexpression of all LipA variants significantly enhanced BHET degradation. All variants were expressed in E. coli for purification and biochemical analysis. The optimum conditions were determined as pH 7 and 25 °C for all variants. The activity on BHET and amorphous PET film was investigated. S2LipA efficiently degraded BHET and caused roughening and indents on the surface of PET films, comparable to the activity of previously described TfCut2 under the same conditions. The abundance of the S2LipA variant in Streptomyces suggests an environmental advantage towards the degradation of more polar substrates including these polluting plastics.

The sexually antagonistic genes of Drosophila melanogaster.

When selective pressures differ between males and females, the genes experiencing these conflicting evolutionary forces are said to be sexually antagonistic. Although the phenotypic effect of these genes has been documented in both wild and laboratory populations, their identity, number, and location remains unknown. Here, by combining data on sex-specific fitness and genome-wide transcript abundance in a quantitative genetic framework, we identified a group of candidate genes experiencing sexually antagonistic selection in the adult, which correspond to 8% of Drosophila melanogaster genes. As predicted, the X chromosome is enriched for these genes, but surprisingly they represent only a small proportion of the total number of sex-biased transcripts, indicating that the latter is a poor predictor of sexual antagonism. Furthermore, the majority of genes whose expression profiles showed a significant relationship with either male or female adult fitness are also sexually antagonistic. These results provide a first insight into the genetic basis of intralocus sexual conflict and indicate that genetic variation for fitness is dominated and maintained by sexual antagonism, potentially neutralizing any indirect genetic benefits of sexual selection.

Intravenous pyogenic granuloma of the right adrenal gland: report of a case.

Pyogenic granuloma (PG) is a tumor-like lesion that typically arises on human skin. Intravenous pyogenic granuloma (IVPG) is the vascular counterpart, mostly observed in the venous structures of the neck and upper extremities. Chronic irritation of the skin, traumatic injury, and hormonal alterations seem to be implicated in the pathogenesis of PG. The incidence of PG, and IVPG, is very low in the reported scientific literature, and this underlines the need for understanding unresolved questions concerning the uncommon presentation, and correct diagnosis before surgical intervention. This report describes a case of IVPG diagnosed in a 55-year-old female that presented for observation of chronic abdominal pain associated with nausea and anorexia. A well-defined mass located in the right adrenal gland was documented by ultrasonography and finally confirmed by contrast enhanced CT of the abdomen. There were no radiological signs of liver, kidney, or vascular infiltration. The 35 × 22 mm adrenal gland lesion, suspected to be an adrenal gland tumor, was resected using a minimally invasive approach. Laparoscopic right adrenalectomy was successfully performed. The histology documented the typical morphological features of IVPG in the context of a normal right adrenal gland. This report describes and discusses the unusual presentation of intraabdominal IVPG located in the adrenal gland region together with a review of the current literature.

Determination of Ligand-Binding Affinity (Kd) Using Transverse Relaxation Rate (R2) in the Ligand-Observed 1H NMR Experiment and Applications to Fragment-Based Drug Discovery.

High hit rates from initial ligand-observed NMR screening can make it challenging to prioritize which hits to follow up, especially in cases where there are no available crystal structures of these hits bound to the target proteins or other strategies to provide affinity ranking. Here, we report a reproducible, accurate, and versatile quantitative ligand-observed NMR assay, which can determine Kd values of fragments in the affinity range of low µM to low mM using transverse relaxation rate R2 as the observable parameter. In this study, we examined the theory and proposed a mathematical formulation to obtain Kd values using non-linear regression analysis. We designed an assay format with automated sample preparation and simplified data analysis. Using tool compounds, we explored the assay reproducibility, accuracy, and detection limits. Finally, we used this assay to triage fragment hits, yielded from fragment screening against the CRBN/DDB1 complex.

Cathepsins and pancreatic cancer: the 2012 update.

Pancreatic cancer is the result of distinctive genetic and epigenetic disturbances. This multistep process is in part well-defined and includes alterations in oncogenes and suppressor genes that control proliferation, apoptosis, angiogenesis, invasion and cell migration. Cathepsins are proteolytic enzymes and represent potential therapeutic targets in human tumors. Cathepsins predominantly function as endopeptidases within endolysosomal vesicles of normal cells and they are involved in physiological processes such as protein turnover, differentiation and apoptosis. In various types of malignancies, cathepsins have been associated with tumor progression and metastasis. Growing evidence and direct proofs suggest that cathepsins are highly up-regulated in pancreatic cancer and contribute to the development and progression of the cancer phenotype. In this review, the role of cathepsins in pancreatic cancer tumorigenesis is reported and discussed. Some critical aspects will be underlined such as specificity of cathepsin activity in pancreatic cancer and in its precursor lesions; the genetic perturbation and the intracellular signaling pathway activated by cathepsins as reported in preclinical models and in human tissues; the preliminary results and the oncological effects of cathepsin inhibitors currently tested on pancreatic cancer cells; the role of combined therapy based on chemotherapeutic agents and cathepsin inhibition. Although mounting evidences indicate that cysteine cathepsins are potential therapeutic targets in pancreatic cancer, as suggested by their functional role in controlling invasiveness and metastasis, it remains to be seen whether the promising benefits of pharmacological inhibitors observed in preclinical study might be translated to the current clinical practice.

Synthesis of amino-substituted indoles using the Bartoli reaction.

We report herein the concise preparation of a range of functionalised aminoindoles via a new application of the Bartoli reaction. Scope and limitations of the methodology have been extensively studied to reveal the importance of protecting groups and substitution patterns. The use of amino substituted nitroanilines for the Bartoli reaction is to our knowledge unprecedented. Our work thus represents a novel entry into substituted aminoindoles which are relevant building blocks for both the fine chemical and pharmaceutical industry.

Struma ovarii with follicular thyroid-type carcinoma and neuroendocrine component: case report.

Struma ovarii (SO) is a slow-growing ovarian neoplasm with thyroid tissue as its predominant component. It is an uncommon neoplasm, usually asymptomatic with an unknown risk of malignant transformation. Due to difficulties in assessing the rare biological nature and the discrepancies in the reported cases, a consensus on the appropriate treatment has not been definitively reached. A 50-year-old female was subjected to upper gut endoscopy which showed a 30-mm mass located in the gastric antrum, suggestive of mesenchimal tumor. Incidentally, a pelvic CT scan also documented a solid mass in the right adnexa, with morphological characteristics of ovarian neoplasm. The patient underwent gastrectomy, total hysterectomy, bilateral salpingo-oophorectomy with lymph node dissection, and omentectomy. Histology documented the presence of gastric cavernous angioma, and, in the right adnexa, foci of follicular thyroid-type carcinoma arising in SO with a well-differentiated neuroendocrine component.Here we report and discuss the clinical and morphological presentation of follicular thyroid-type carcinoma arising in SO. The neoplasm was discovered incidentally and had a favorable clinical outcome at 1-year follow-up.

Risk factors for conversion of laparoscopic cholecystectomy.

BACKGROUND: Conversion during laparoscopic cholecystectomy has adverse effects on operating time, postoperative morbidity and hospital costs. Identifying risk factors for conversion is thus important to help surgeons to plan and counsel the patient and arranging operating schedules accordingly. This study evaluated retrospectively preoperative and intraoperative risk factors for conversion in 906 laparoscopic cholecystectomies for gallbladder calculosis. METHODS: Examined preoperative variables were: age, sex, obesity, arterial hypertension, diabetes, previous acute myocardial infarction, chronic obstructive pulmonary disease, non-ischemic heart disease, chronic hepatitis, hepatic cirrhosis, previous pancreatitis, biliary colics, endoscopic retrograde cholangiopancreatography (ERCP) and abdominal or cardiac surgery,as well as pain, fever, a high white blood cell count, ultrasound signs of cholecystitis at hospitalization. Intraoperative variables were: adhesiolysis, associated hepatic biopsy. RESULTS: Twenty-five operations were converted (conversion rate: 2.76%). Factors significantly associated with conversion were: age over 60 years, diabetes, previous supramesocolic abdominal surgery, ultrasound signs of cholecystitis, white cell count over 9x10(3)/dl, previous acute myocardial infarction and preoperative ERCP, intraoperative adhesiolysis (0.001

Recent Advances in the Development of Semisynthetic Glycopeptide Antibiotics: 2014-2022.

The accelerated appearance of drug-resistant bacteria poses an ever-growing threat to modern medicine's capacity to fight infectious diseases. Gram-positive species such as methicillin-resistant Staphylococcus aureus (MRSA) and Streptococcus pneumoniae continue to contribute significantly to the global burden of antimicrobial resistance. For decades, the treatment of serious Gram-positive infections relied upon the glycopeptide family of antibiotics, typified by vancomycin, as a last line of defense. With the emergence of vancomycin resistance, the semisynthetic glycopeptides telavancin, dalbavancin, and oritavancin were developed. The clinical use of these compounds is somewhat limited due to toxicity concerns and their unusual pharmacokinetics, highlighting the importance of developing next-generation semisynthetic glycopeptides with enhanced antibacterial activities and improved safety profiles. This Review provides an updated overview of recent advancements made in the development of novel semisynthetic glycopeptides, spanning the period from 2014 to today. A wide range of approaches are covered, encompassing innovative strategies that have delivered semisynthetic glycopeptides with potent activities against Gram-positive bacteria, including drug-resistant strains. We also address recent efforts aimed at developing targeted therapies and advances made in extending the activity of the glycopeptides toward Gram-negative organisms.

Acute esophageal necrosis syndrome. The 2021 update from an Italian survey and personal experience.

AIM: Black esophagus, or acute esophageal necrosis, is a rare entity with multifactorial aetiology. Modern theories suggest a combination of ischemia, compromised mucosa defences and corrosive agent's injury. MATERIAL AND METHODS: We investigated black esophagus by means of a retrospective review of 26 cases in literature. A Medline overview is performed until May 2021 by considering the Italian results. The search terms were "black esophageal syndrome in Italy", "black esophagus in Italy", "black esophageal necrosis in Italy", and "Gurvits syndrome in Italy". To complete these case reports, we illustrate our first experience of the syndrome successfully treated with esophagectomy, cervical diversion and gastrostomy. RESULTS: Black esophagus is common in adult males (M/F: 21/5) (Range: 47-89 years; Average: 70.6 year-old). The most common symptoms are hematemesis, epigastric pain and dysphagia. Endoscopically, diffuse involvement of acute esophageal necrosis is diagnosed in 42.3% of cases. The treatment consisted on red blood cell transfusions, sucralfate administration, proton pump-inhibition, enteral nutrition and antimicrobial agents. Overall mortality was 38.4% and only one case underwent surgery for acute bleeding. CONCLUSIONS: Black esophagus is often reversible both anatomically and functionally. Its treatment is based on supported therapies and hemodynamic resuscitation. This syndrome shows high mortality related to the coexisted medical conditions rather than acute esophageal necrosis. Only in selected cases, surgical treatment is indicated. KEY WORDS: Acute necrotizing esophagitis, Black esophagus, Ischemia.